Podcasts about vaccinia

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.02.24.529907v1?rss=1 Authors: Basant, A., Way, M. Abstract: Vaccinia virus exiting from host cells activates Src/Abl kinases to phosphorylate A36, an integral membrane viral protein. Phosphorylated A36 binds the adaptors Nck and Grb2 which recruit N-WASP to activate Arp2/3-driven actin polymerisation to promote viral spread. A36 also recruits intersectin, which enhances actin polymerization via AP-2/clathrin and Cdc42. To obtain a better quantitative understanding of this signalling network we still need to know the absolute numbers of the key molecules. To achieve this goal, we have now used fluorescent molecule counting approaches in live cells. There are 1156{+/-}120 A36 molecules on virus particles inducing actin polymerization in HeLa cells. This number, however, is over 2000 in mouse embryonic fibroblasts (MEFs), suggesting that A36 levels on the virion are not fixed. In MEFs, viruses recruit 1032{+/-}200 Nck and 434{+/-}10 N-WASP molecules, suggesting a ratio of 4:2:1 for the A36:Nck:N-WASP signalling network. Loss of A36 binding to either Grb2 or intersectin results in a 1.3- and 2.5-fold reduction in Nck respectively. Despite recruiting comparable numbers of the Arp2/3 activator, N-WASP (245{+/-}26 and 276{+/-}66), these mutant viruses move at different speeds that inversely correlate with the number of Nck molecules. Our analysis has uncovered two unexpected new aspects of Vaccinia egress, A36 levels can vary in the viral membrane and the velocity of virus movement depends on Nck. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.02.04.527154v1?rss=1 Authors: Liu, W., Lu, J.-Y., Wang, Y.-J., Xu, X.-x., Chen, Y.-C., Yu, S.-X., Xiang, X.-W., Chen, X.-Z., Jiu, Y., Gao, H., Sheng, M., Chen, Z.-J., Hu, X., Li, D., Maiuri, P., Huang, X., Ying, T., Xu, G.-L., Pang, D.-W., Zhang, Z.-L., Liu, B., Liu, Y.-J. Abstract: The emerging outbreak of monkeypox is closely associated with the viral infection and spreading, threatening global public health. Virus-induced cell migration facilitates viral transmission. However, high-resolution dynamics and mechanisms underlying this type of cell migration remain unclear. Here, we investigate the motility of cells infected by vaccinia virus (VACV), a close relative of monkeypox, through combining multi-omics analyses and high-resolution live-cell imaging. We find that, upon VACV infection, the epithelial cells undergo EMT-like transformation, during which they lose intercellular junctions and acquire the migratory capacity to promote viral spreading. After transformation, VACV-induced mesenchymal migration is highly dependent on the actin cytoskeleton and RhoA signaling, which is responsible for the depolymerization of robust actin stress fibers, the leading-edge protrusion formation, and the rear-edge recontraction. Our study reveals how poxviruses alter the epithelial phenotype and regulate RhoA signaling to induce fast migration, providing a unique perspective to understand the pathogenesis of poxviruses. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Vidcast:  https://youtu.be/VQj4zPuGqdY   We've talked about a twindemic this spring of both CoVid and Influenza, but now we have monkeypox threatening to make it a tridemic.  So what should you know about monkeypox?   Monkeypox is an orthopoxvirus, a cousin of the smallpox virus, that was first identified in 1958 in a colony of African monkeys.  The first human case was noted in 1970, again in Africa, and the majority of infections occur in the Democratic Republic of the Congo.  The virus is mostly carried by rodents such as mice, rats, and squirrels.   Monkeypox does not occur naturally in the US, and all cases here stem from International travelers bringing in the virus.  As of June 1st, monkeypox cases have been identified in 10 states and in more than 23 countries.   Monkeypox begins with typical symptoms of viral infections including fever, headache, muscle aches, and fatigue after a 5 to 21 day incubation period.  One to three days after symptom onset, a rash appears followed by discrete lesions that become bumpy, liquid-filled, and pus-filled, that break giving way to scabs after a total of 2 to 4 weeks.     The disease is spread by infected secretions during close and intimate contact including sex but may also be spread through respiratory secretions.  Spread is prevented by avoiding contact with sick animals and people, careful hand washing and use of alcohol hand sanitizers, and masking as well as use of eye protection around those who are infected.  The very young, elders, pregnant women, and those with immune deficiencies are at particular risk.   Those previously immunized against smallpox should have some protection, but it likely has waned over time.  Most at risk currently are younger persons who never received the smallpox vaccine.  At this time, vaccination is not being recommended but that may change if the disease is spreading.  If it is, problems will arise as available vaccines to monkeypox, JYNNEOS and the older ACAM200, are in short supply.   There are several anti-viral medications, tecovirimat and brincidofovir, that counteract monkeypox, but their effectiveness in treating human monkeypox has not been proven.  Vaccinia immune globulin is available and may provide effective treatment for those infected.  To prevent spread, any infected person should quarantine for 21 days.   https://www.cdc.gov/poxvirus/monkeypox/treatment.html   #Monkeypox #smallpox #vaccinia #tecovirimat #brincidofovir  

From 1987, did Vaccinia cause AIDS? The Irish thought so. Mainstreams finally admitted the shots “impair long-term immunity”. Dr. Mike Yeadon weighs in on what the shot does to the ovaries. The Brownstone Institute reveals the global QR digital ID from Deutsche Telekom that the WHO wants for 7.5B humans.

La viruela del mono, como os dijimos ayer, es un virus similar al que causa la viruela en humanos y la viruela bovina. En esta familia de virus también encontramos el Vaccinia virus que fue utilizado para crear la vacuna contra la viruela, gracias a su parecido.Como todos estos virus, el virus de la viruela del mono presenta unas característicassimilares, tanto en su estructura como en los síntomas que genera.Este virus es zoonótico, lo que quiere decir que su reservorio natural es en animales.Entre los animales más comunes encontramos ratas, ardillas y otros roedores, aunqueel principal reservorio todavía no se ha identificado.Suscríbete a Muy Interesante https://suscripciones.zinetmedia.es/mz/ Guión: Marta González Pérez-IñigoLocución, producción y diseño sonoro: Iván Patxi Gómez GallegoContacto de publicidad en podcast: podcast@zinetmedia.es

Jared Brock's Future Faith podcast is also available for free on Spotify and Apple Podcasts.I've been avoiding publishing any articles on vaccines because it's an absurdly contentious subject that wins you no friends and makes you quite a few enemies.It's an issue plagued with political ideologies, conflicts of interests, bad faith arguments, issue conflation, terrible research, and appallingly stupid false dichotomies.But alas, my inbox has been flooded with good folks asking me my perspective, so hopefully, I can lay it all out in one article and never have to discuss it again. My guess is that this will be one of the most contentious pieces I ever publish, so even if you disagree but can manage to stick with me through this one, I think we can continue our relationship for years to come!In this piece, I'm going to try and lay out a biblical framework for approaching issues like this. I have no financial incentives in this fight, and I want to make it clear that my goal isn't to make you get a vaccine or not get a vaccine, but to help tune up our reasoning and look at this highly-contentious subject through a Christ-centered lens.Let's start at the beginning“A very good place to start.” — Maria von Trapp in The Sound of MusicThere are a lot of people out there who think vaccines are “inherently dangerous because there is no long-term safety data.”These people have never read a history book.Let's go back in time…The year is 1774. Smallpox is ravaging the world. Sore throats, headaches, and difficulty breathing are the nice symptoms. Instead, disfiguring rashes cover most infected people's faces, feet, throat, and lungs with pus-filled pustules. A third of adults infected will die. Eight in ten infants will die. At least 400,000 people will die per year for decades, and survivors will be marred with blindness and lifelong scars, driving some to suicide.Here's what that looks like in real life:People tried everything to halt smallpox outbreaks — hot rooms, cold rooms, avoiding melons, wearing the color red, drinking twelve beers per day. None of it worked, of course, but there was one genuine cure — an ancient practice from India and Africa called “variolation” an early form of inoculation. We even know the name of the African slave who brought the life-saving practice to North America. His name was Onesimus, likely named after the slave mentioned in Colossians and Philemon. The American Onesimus's master convinced 287 Bostonians to get variolated — among the inoculated, their rates of death fell sevenfold.Variolation is pretty freaky by today's standards: People just took pus from someone suffering from smallpox and scratched it into the skin of healthy folks. During the American Civil War, people would take the dried scabs of smallpox survivors, grind them into powder, then sniff it up the nose or drink it in tea.Variolation worked… ish. People would usually get a mild case of smallpox and survive, thanks to their well-prepped immune systems. Some people still got full-blown smallpox and died, but variolation increased your chances of survival.Over in rural England, one class of person seemed completely immune to smallpox: milkmaids. The women occasionally suffered from a cattle disease called cowpox, but they usually survived with little scarring. In 1774, as a smallpox epidemic once again swept his nation, farmer Benjamin Jesty decided to scratch some cow pus into his family's skin.None of them got smallpox.The science was and is simple: The cowpox pus — vaccinia — could create antibodies and genetic memory that would trigger the human body to create immunity against life-threatening pathogens.Ben Jesty renovated his garden cottage into a “Temple of Vaccinia” and invited locals to visit after church for their life-saving doses. For his generosity, he was labeled inhuman, “hooted at, reviled, and pelted whenever he attended markets in the neighborhood,” with some neighbors even worrying he'd turn them into horned beasts.Because of a lack of widespread and effective vaccination, 300 million people died in the 20th century from smallpox alone.A resounding successWe now have nearly 250 years of data and it all says the same thing: Vaccination decreases your chances of dying from deadly pathogens.* We no longer have regular rolling rounds of smallpox, whooping cough, scarlet fever, polio, hib, cholera, and other deadly diseases that have killed tens of millions of people across time.* Since 1962 alone, 4.5 billion virus cases have been averted thanks to modern vaccinations.* Tetanus mortality has been reduced by 96% since 1988.* 17.1 million lives have been saved from measles since 2000.* Smallpox has been completely eradicated.To be anti-vaccination is the same as saying you're anti-medicine.Thankfully, the vast majority of the world understands that vaccination is medicine. 9 out of 10 people in the world think that vaccinating children is important.But there's a small but vociferously vocal minority — typically white, right-leaning, Westerners who have never lost a child to a life-threatening pathogen — who would rather risk their family's life and safety than give them this particular form of medicine.They have about five major reasons, but none of them are Socratically sound:1. Therapeutics aren't a good enough reason to reject vaccine therapySome of our more earthy brothers and hippie sisters think we should stop playing God and just let nature do its thing, building our immune systems naturally.Which is exactly what vaccines do.Innoculation comes from the Middle English word “inoculaten,” which means “grafting a plant part to another plant.” When we get a vaccine, we're essentially grafting some of the enemy pathogens into our immune system, but in a way that teaches our body to do the miraculous work of defending itself when the real pathogen shows up.Most football coaches don't let their teams go onto the field until they've analyzed the competition for weaknesses. Most militaries don't send their soldiers into battle until they know their enemy's setup. I hate to use computer terms for something as gloriously biological as a homo sapiens, but human bodies are old hardware in need of constant software updates.Some people think our updates should only come from therapeutics and not inoculations.But don't forget Brock's Rule! Avoid false dichotomies.When given two bad options, choose neither.When given two good options, choose both.Don't fall prey to the false dichotomy that it's one or the other, therapeutics versus vaccinations.Clearly, governments should have instituted a two-year ban on fast food, high fructose corn syrup, added sugars, processed foods, and everything non-organic, then sent everyone to the woods and beaches for exercise and sunlight while scientists worked on a vaccine.And if you're so inclined, go ahead and take therapeutics — sniff all the essential oils and eat all the vitamins to try to build a killer immune system, and also get the vaccine… which is just another natural immune booster.If our rationale for therapeutics is truly to boost our natural immunity, then vaccines are the #1 weapon in our arsenal for doing so. The Cambridge dictionary defines a therapeutic as anything “tending to make a person healthier.” Vaccinations are therapeutic.2. Big Pharma profits aren't a good enough reason to reject vaccine therapyBig Pharma is awful.Life-saving medicine shouldn't be a money-making industry.There should be zero for-profit vaccines.Pfizer and the other drug cartels are making billions off Covid, and it's not right.I wonder how many more anti-vaxxers would take vaccine therapy if it was owned and administered by democratic governments, not-for-profits, and charities. Imagine how many more people would get vaccinated if the Red Cross did the deed at their local church.But alas, here we are.We need to ask the same question as Cicero and the ancient Romans:Cui bono? Who profits?Clearly, Big Pharma is reaping a waterfall of cash from their vaccine. That's a huge issue we must address.But it doesn't mean vaccines are any less effective.What's interesting is that many anti-vaxxers are happy to take all sorts of other for-profit products — literally anything under the sun, including anti-malarial hydroxychloroquine and a mostly Chinese-producedlice medication (and horse de-wormer) called Ivermectin.Who do they think is paying for all the marketing and social media posts they're reading about these products?Who do they think profits from every single therapeutic purchase they make?It's just shadow Big Pharma.(Ironically, one of Ivermectin's biggest manufacturers… is also a vaccine maker.)There are profit motives on both sides — clearly, Big Pharma's profits are far larger because they have so many unfair advantages — but it doesn't mean vaccines are any less effective. Vaccines don't care who makes money off them; they simply decrease our chances of dying from deadly pathogens.3. Economic re-engineering isn't a good enough reason to reject vaccine therapyCorporate elites have used this pandemic as an excuse to enrich themselves to the tune of $5.5 trillion and growing.We clearly have to deal with this.We need a wealth tax, a global minimum corporate tax, and a robot tax.Otherwise, the Great Reset will leave us all as full-time wage-slaves and rent-slaves.But wealth inequality and systemic impoverishment also have nothing to do with vaccination efficacy.Vaccines decrease our chances of death, regardless of who dominates the economy and tries to grind the middle class to dust.4. The risk of a superbug isn't a good enough reason to reject vaccine therapyThere's also the very bad argument that taking vaccines will eventually create some sort of vaccine-resistant superbug. While the odds of such a pathogen eventually existing is extremely high, the argument itself is extremely poor for two big reasons:First, this argument naturally forces the anti-vaxxer to admit that vaccines have, up until this point in time, indeed worked.Second, when that vaccine-resistant pathogen does arrive, millions of people will die and no vaccine will help — and neither will the immune systems of millions of anti-vaxxers. There's no evidence that says people who've avoided vaccines their whole lives will magically be granted immunity from the superbug.I've met people who literally believe no one should take vaccines and we should risk the annual loss of millions of lives in an effort to boost our collective immune system. This, frankly, is unacceptable in a pro-human society. Sure, it would be great if our immune systems naturally adapted as fast as viruses do, but they don't. Christ-followers can't in good faith permit millions of deaths when we have a suboptimal but effective immune-training technology in our possession. That would be like withholding a life-preserver from a drowning person today because there might be a tsunami in the future.We cannot allow the delusional perfect to be the enemy of the concrete good. The Bible is very clear that the earth is currently in a fallen state. In heaven, we won't need vaccines. On earth, we clearly do.5. Covid passports aren't a good enough reason to reject vaccine therapyThis is the big one, isn't it?It's certainly the thing everyone keeps emailing and calling me about.“Aren't Covid passports just the tip of the spear for government surveillance?”No, they're not.We're way past that.A vaccine passport is a joke compared to your smartphone, your digital bank, your social media, your Internet usage history, and especially the coming central bank digital currencies (CBDCs) and social credit systems.Don't lose the plot, friends. Vaccines aren't the “tip of the spear” whatsoever. That weapon belongs to the elite monopoly control of money-creation. Everything else is secondary.And here's a big thing a lot of non-travelers have forgotten:We've already had vaccine passports for years.My wife and I have traveled to plenty of risky places including North Korea, Transnistria, Honduras, Ethiopia, and West Texas. Tourists who only go to Florida and Hawaii and Caribbean all-inclusives may not realize it, but much of the world has required proof of vaccination for decades.As any missionary kid knows, you can't get into many countries without showing your doctor-stamped visa that proves you've had your yellow fever shots. 124 nations require you to show a yellow fever vaccine visa to get across their borders. We've shown ours many times. (We've also never had yellow fever, which still kills 30,000 people per year, because our vaccination gave us 99% immunity 30 days after injection.)Yes, future vaccine visas will likely be logged on the blockchain and movement will be automatically restricted by robots and algorithms. This is anti-human and should rightly be outlawed. But avoiding vaccination itself won't change this. It's the wrong hill to die on.Tyranny isn't defeated by leaving your immune system under-educated.Why vaccines are so politicalIf Covid had a 100% transmission rate and a 100% kill rate, we wouldn't be having this conversation.If any disease spread to everyone and killed everyone, everyone except suicidal sociopaths would be in favor of mandated vaccination and proven containment measures.Conversely, if a “disease” had a 0% kill rate and a 0% transmission rate, none of us would be in favor of any vaccination or any containment measure.Clearly, it's just a sliding scale, based on personal risk tolerance.So the question is: Who gets to decide when we should mandate vaccines and when to implement containment measures?Ebola has a 50+% kill rate, but a low transmission rate. The vaccine is effective 97.5% of the time. If it had a 90% transmission rate by simply breathing in public, would you mandate a vaccine and/or try to implement containment measures? Even though we live in a troublingly individualist anti-culture, most people would say yes.(If it were solely up to me, for the sake of stopping variants, vaccines would be mandatory for any contagious disease with an R-nought of more than 1.27 and/or an Infection Fatality Rate of more than 0.038%. If someone doesn't like it, they can move to Arkansas.)But it's not up to me, of course.And it's not up to you.Because we can all infect each other, it's only fair that we all get to decide.Vaccine regulation is democracy's job.And people are actually furious because they don't live in a democracy.Let's be honest about what this is really all about:Thisisallabouttrust.The vaccine debate has almost nothing to do with health:People don't trust Big Pharma.Nor should they — if it were up to Big Pharma, we'd all die unless we could pay top “free”-market dollar for their wares. They already do this in unregulated nations in Africa.People don't trust Big Medicine.Nor should they — the American for-profit healthcare system is the biggest scam in global health.People don't trust Big Government.Nor should they — we live in an undemocratic corporatocracy ruled by private interests with anti-commons agendas.The Bible is quite clear in Psalm 146:3 “Do not put your trust in princes; there is no hope for you there.”But our distrust of government has nothing to do with vaccine therapy.We need to think clearly about the big picture: We're rapidly approaching the age of the panopticon surveillance state.So long as we continue to buy from giant corporations and vote for their corporate-captured political parties and candidates, social credit systems are coming, with or without a vaccine passport.Vaccines are an opportunityAs far as I can see it, vaccination provides Christ-centered people with five intriguing opportunities:1. The opportunity to serve othersJust because some of us feel young, strong, and healthy doesn't mean we aren't surrounded by more vulnerable people, especially the elderly brothers and sisters in our churches. In Philippians 2:5–7, Paul encourages us that, “In your relationships with another, have the same mindset as Christ Jesus by taking the very nature of a servant, not looking to your own interests but each of you to the interests of the others.” Supercharging our immune systems is yet another way we can serve each other.One thing is for certain: Vaccinations aren't worth losing unity over. As Paul wrote to the Corinthians: “I appeal to you, brothers and sisters, in the name of our Lord Jesus Christ, that all of you agree with one another in what you say and that there be no divisions among you, but that you be perfectly united in mind and thought.” The reality is that vaccine passports are just the next technology that secularist governments may try to use to control their citizens. These new technologies are emerging at a faster and faster rate, which suggests Jesus-followers actually need to slow down, get in step with the Holy Spirit, and wrestle together as Christ-centered communities on how to honor God in this cultural moment.2. The opportunity to obey our governmentsThis one is very, very tough for those of us who've been raised in this hyper-selfish individualist anti-culture.But Scripture is brutally clear on this point: we are to obey every government law that doesn't disobey God's law. Titus 3:1 — “Remind the people to be subject to rulers and authorities, to be obedient, to be ready to do whatever is good, to slander no one, to be peaceable and considerate, and always to be gentle toward everyone.” 1 Peter 2:13–15 — “Be subject for the Lord's sake to every human institution, whether it be to the emperor as supreme, or to governors… For it is God's will that by doing good you should silence the ignorant talk of foolish people.”Clearly, getting vaccinated doesn't go against the word of God and the gospel of Christ. In fact, it creates obedience to 1 Corinthians 6:19, where Paul insists our bodies are temples of the Holy Spirit. But if you're like me, you have a deeply rebellious spirit! This is our opportunity to submit to the government. Believe me, there will soon be plenty of reasons to glorify God by practicing civil disobedience, but avoiding vaccination isn't one of them.3. The opportunity to honest and truthfulWe don't need to delude ourselves into thinking we're “educated” on vaccines. The vast majority of us don't have a doctorate in the subject, and no amount of online article-reading will ever get us there. We don't argue about whether or not houses reliably stay standing — they generally do, and we don't need to research the intricacies of house-engineering to trust the experts. In the same, we know that vaccines have proven to boost our immunes systems for the past few centuries, and while they aren't perfect, that's probably all a lay-person needs to know. This is an opportunity to lay aside the notion that we are experts on this subject. As Mark Twain said, “It ain't what you don't know that gets you into trouble. It's what you know for sure that just ain't so.”4. The opportunity to practice wisdomPastor Andy Stanley says that the best question ever is, “In light of our past experiences, current circumstances, and future hopes and dreams, what is the wisest thing to do?”This isn't a question to answer alone. Followers of the Way will naturally do what we always do when faced with tough questions: Go to the Word, get on our knees, and meet with other believers.Only the Holy Spirit can guide us into all truth.5. The opportunity to wear a cloak of humilityThis is our chance to not think better of ourselves than we should. Having the vaccine doesn't make you a better person — it just means you're less likely to die from Covid-19.In the same way, not having the vaccine doesn't make you better than your vaccinated brothers and sisters — it just means you're putting them and yourself at a greater risk of infection.Remember: Christ-followers don't have human enemies. We are called to love those who hate us, and pray for those who persecute us. As John Mark Comer says, we are to make our bodies a graveyard for hate.For pastors and elders, there is a huge opportunity to disciple your believers toward a less individualistic outlook on life, re-orienting your people to a communal framework for living, and a proper understanding of the government's role in the life of a Jesus-follower.In ConclusionRegardless of mandates or economics or passports, I would've gotten the Covid vaccine anyway. Why? Because vaccination helps train my God-given immune system to be awesome, and because this vaccine is proven to significantly decrease my chance of death by Covid.That's it.Vaccines just aren't political for me, at all. I can't fathom why anyone makes them political — vaccines are therapeutic medicine that trains your body to fight pathogens, pure and simple. Sadly, ours is an age of outrageous conflation. Rather than thinking clearly and tackling the real problems of tyranny, we endanger our children because we think it's magically “creating change.”My track record shows that I'm extremely anti-partisan, anti-politician, and anti-corporatocracy, and I'm not going to let any tyrannical earthly institution weaponize my own health against me.We need to stay strong so we can take down the powers and principalities who are actively at work in the spiritual realm.This often ugly debate should make us ask important questions:* Am I placing my trust in the government, myself, or my Savior?* Am I spending more time on social media than in God's word?* Do I spend more time researching vaccines than I do in prayer?* Would I rather fight digital people on the Internet more than commune with local believers in the flesh?At the end of the day, everything always comes back to the gospel. The good news is that the kingdom of God is here in our midst; that Christ has taken our sin on his shoulders; that through Him we can be restored to God. This has massive implications for how we live and move and have our being.As you wrestle with the Word and the Holy Spirit and your church through this issue, I pray that you will find unity and peace in the bonds of His love. Get full access to Future Faith at jaredbrock.substack.com/subscribe

Welcome to Surviving Tomorrow, a podcast, newsletter, and publication that helps you navigate life in an age of democratic destruction, ecological collapse, and economic irrelevance, available for FREE on Substack, Spotify, Apple Podcasts, Facebook, and Youtube.I've been avoiding publishing any articles on vaccines because it's an absurdly contentious subject that wins you no friends and makes you quite a few enemies.It's an issue plagued with political ideologies, conflicts of interests, bad faith arguments, issue conflation, terrible research, and appallingly stupid false dichotomies.But alas, my inbox has been flooded with good folks asking me my perspective, so hopefully, I can lay it all out in one post and never have to discuss it again.Lucky me.Let's start at the beginning“A very good place to start.” — Maria von Trapp in The Sound of MusicThere are a lot of people out there who think vaccines are “inherently dangerous because there is no long-term safety data.”These people have never read a history book.Let's go back in time…The year is 1774. Smallpox is ravaging the world. Sore throats, headaches, and difficulty breathing are the nice symptoms. Instead, disfiguring rashes cover most infected people's faces, feet, throat, and lungs with pus-filled pustules. A third of adults infected will die. Eight in ten infants will die. At least 400,000 people will die per year for decades, and survivors will be marred with blindness and lifelong scars, driving some to suicide.Here's what that looks like in real life:People tried everything to halt smallpox outbreaks — hot rooms, cold rooms, avoiding melons, wearing the color red, drinking twelve beers per day. None of it worked, of course, but there was one genuine cure — an ancient practice from Africa called “variolation” an early form of inoculation. (We even know the name of the African slave who brought the life-saving practice to North America.)Variolation is pretty horrific by today's standards: People who take pus from someone suffering from smallpox and scratch it into the skin of healthy folks. During the American Civil War, people would take the dried scabs of smallpox survivors, grind them into powder, then sniff it up the nose or drink it in tea.Variolation worked… ish. People would usually get a mild case of smallpox and survive, thanks to their well-prepped immune systems. Some people still got full-blown smallpox and died, but variolation increased your chances of survival.Over in rural England, one class of person seemed completely immune to smallpox: milkmaids. The women occasionally suffered from a cattle disease called cowpox, but they usually survived with little scarring. In 1774, as a smallpox epidemic once again swept his nation, farmer Benjamin Jesty decided to scratch some cow pus into his family's skin.None of them got smallpox.The science is simple: The cowpox pus — vaccinia — could create antibodies and genetic memory that would trigger the human body to create immunity against life-threatening pathogens.Ben Jesty renovated his garden cottage into a “Temple of Vaccinia” and invited locals to visit after church for their life-saving doses. For his generosity, he was labeled inhuman, “hooted at, reviled, and pelted whenever he attended markets in the neighborhood,” with some neighbors even worrying he'd turn them into horned beasts.Because of a lack of widespread and effective vaccination, 300 million people died in the 20th century from smallpox alone.A resounding successWe now have nearly 250 years of data and it all says the same thing: Vaccination decreases your chances of getting and dying from deadly pathogens.We no longer have regular rolling rounds of smallpox, whooping cough, scarlet fever, polio, hib, cholera, and other deadly diseases that have killed tens of millions of people across time.Since 1962 alone, 4.5 billion virus cases have been averted thanks to modern vaccinations.Tetanus mortality has been reduced by 96% since 1988.17.1 million lives have been saved from measles since 2000.Smallpox has been completely eradicated.To be anti-vaccination is the same as saying you're anti-medicine.Thankfully, the vast majority of the world understands that vaccination is medicine. 9 out of 10 people in the world think that vaccinating children is important.But there's a small but vociferously vocal minority — typically white, right-leaning, poorly-educated Westerners who are addicted to social media and have never lost a child to a life-threatening pathogen — who would rather risk their family's life and safety than give them this particular form of medicine.They have their reasons, but none of them are Socratically sound:Therapeutics aren't a good enough reason to reject vaccine therapySome of our more earthy brothers and hippie sisters think we should stop playing God and just let nature do its thing, building our immune systems naturally.Which is exactly what vaccines do.Innoculation comes from the Middle English word “inoculaten,” which means “grafting a plant part to another plant.” When we get a vaccine, we're essentially grafting some of the enemy pathogens into our immune system, but in a way that teaches our body to do the miraculous work of defending itself when the real pathogen shows up.Most football coaches don't let their teams go onto the field until they've analyzed the competition for weaknesses. Most militaries don't send their soldiers into battle until they know their enemy's setup. I hate to use computer terms for something as gloriously biological as a homo sapiens, but human bodies are old hardware in need of constant software updates.Some people think our updates should only come from therapeutics and not inoculations.They're forgetting Brock's Rule: Avoid false dichotomies.When given two bad options, choose neither.When given two good options, choose both.Don't fall prey to the false dichotomy that it's one or the other, therapeutics versus vaccinations.Clearly, governments should have instituted a two-year ban on fast food, high fructose corn syrup, added sugars, processed foods, and everything non-organic, then sent everyone to the woods and beaches for exercise and sunlight while scientists worked on a vaccine.And if you're so inclined, go ahead and take therapeutics — eat all the essential oils and Ivermectin and vitamins to try to build a killer immune system, and also get the vaccine… which is just another natural immune booster. And we know for certain that the vaccine boosts our immunity response to Covid-19: Over a vaccine test group of nearly 28,000 participants — half vaccinated, half placebo — the unvaccinated group had sixteen times as many Covid-19 cases.If our rationale for therapeutics is truly to boost our natural immunity, then vaccines are the #1 weapon in our arsenal for doing so. The Cambridge dictionary defines a therapeutic as anything “tending to make a person healthier.” Vaccinations are therapeutic.Big Pharma profits aren't a good enough reason to reject vaccine therapyBig Pharma is awful.Life-saving medicine shouldn't be a money-making industry.There should be zero for-profit vaccines.Pfizer and the other drug cartels are making billions off Covid, and it's not right.I wonder how many more anti-vaxxers would take vaccine therapy if it was owned and administered by democratic governments, not-for-profits, and charities. Imagine how many more people would get vaccinated if the Red Cross did the deed at their local church.But alas, here we are.The question we need to ask, just like Cicero and the ancient Romans: Cui bono? Who profits?Clearly, Big Pharma is reaping a waterfall of cash from their vaccine. That's a huge issue we must address.But it doesn't mean vaccines are any less effective.What's interesting is that many anti-vaxxers are happy to take all sorts of other purchased products — literally anything under the sun, including anti-malarial hydroxychloroquine and a mostly Chinese-producedlice medication (and horse de-wormer) called Ivermectin.Who do they think is paying for all the marketing and social media posts they're reading about these products?Who do they think profits from every single therapeutic purchase they make?It's just shadow Big Pharma.(Ironically, one of Ivermectin's biggest manufacturers… is also a vaccine maker.)There are profit motives on both sides — clearly, Big Pharma's profits are far larger because they have so many unfair advantages — but it doesn't mean vaccines are any less effective. Vaccines don't care who makes money off them; they simply decrease our chances of getting and dying from deadly pathogens.Economic re-engineering isn't a good enough reason to reject vaccine therapyCorporate elites have used this pandemic as an excuse to enrich themselves to the tune of $5.5 trillion and growing.We clearly have to deal with this.We need a wealth tax, a global minimum corporate tax, and a robot tax.And thousands of Wall Streeters probably need to go to jail.But wealth inequality also has nothing to do with vaccination efficacy.Vaccines decrease our chances of death, regardless of who dominates the economy and tries to grind the middle class to dust.The risk of a superbug isn't a good enough reason to reject vaccine therapyThere's also the very bad argument that taking vaccines will eventually create some sort of vaccine-resistant superbug. While the odds of such a pathogen eventually existing is extremely high, the argument itself is extremely poor for two big reasons:First, it forces the anti-vaxxer to admit that vaccines up until this point have, indeed, worked.Second, when that vaccine-resistant pathogen arrives, millions of people will die and no vaccine will help — and neither will the immune systems of millions of anti-vaxxers. There's no evidence that says people who've avoided vaccines their whole lives will magically be granted immunity from the superbugs.I've met people who literally believe no one should take vaccines and we should risk the loss of millions of lives in an effort to boost our collective immune system. This, frankly, is unacceptable in a pro-human society. Sure, it would be great if our immune systems naturally adapted as fast as viruses do, but they don't. We can't in good faith permit millions of deaths when we have a suboptimal but effective immune-training technology in our possession. That would be like withholding a life-preserver from a drowning person today because there might be a tsunami in the future.We cannot allow the delusional perfect to be the enemy of the concrete good.Covid passports aren't a good enough reason to reject vaccine therapyThis is the big one, isn't it?It's certainly the thing everyone keeps emailing and calling me about.“Aren't Covid passports just the tip of the spear for government surveillance?”No, they're not.We're way past that.A vaccine passport is a joke compared to your smartphone, your digital bank, your social media, your Internet usage history, and especially the coming central bank digital currencies (CBDCs) and social credit systems.Don't lose the plot, friends. Vaccines aren't the “tip of the spear” whatsoever. That weapon belongs to the private monopoly control of money-creation. Everything else is secondary.And here's a big thing a lot of non-travelers have forgotten:We've already had vaccine passports for years.My wife and I have traveled to plenty of risky countries including North Korea, Transnistria, Honduras, Ethiopia, and even West Texas. Tourists who only go to Florida and Hawaii and Caribbean all-inclusives may not realize it, but much of the world has required proof of vaccination for decades.As any missionary kid knows, you can't get into many countries without showing your doctor-stamped visa that proves you've had your yellow fever shots. 124 nations require you to show a yellow fever vaccine visa to get across their borders. We've shown ours many times. (We've also never had yellow fever, which still kills 30,000 people per year because vaccination gives people 99% immunity 30 days after injection.)Yes, future vaccine visas will likely be logged on the blockchain and movement will be automatically restricted by robots and algorithms. This is anti-human and should absolutely be outlawed. But avoiding vaccination itself won't change this. It's the wrong hill to die on.Tyranny isn't defeated by leaving your immune system under-educated.Why vaccines are so politicalIf Covid had a 100% transmission rate and a 100% kill rate, we wouldn't be having this conversation.If any disease spread to everyone and killed everyone, everyone except suicidal sociopaths would be in favor of mandated vaccination and proven containment measures.Conversely, if a disease had a 0% kill rate and a 0% transmission rate, no one would be in favor of any vaccination and any containment measures.Clearly, it's just a sliding scale, based on personal risk tolerance.So the question is: Who gets to decide when we should mandate vaccines and when to implement containment measures?Ebola has a 50+% kill rate. The Ebola vaccine is effective 97.5% of the time. If it had a 90% transmission rate by simply breathing in public, would you mandate a vaccine and/or try to implement containment measures? Even though we live in a troublingly individualist anti-culture, most people would say yes.(If it were solely up to me, vaccines would be mandatory for any contagious disease with an R-nought of more than 1.27 and/or an Infection Fatality Rate of more than 0.038%. If someone doesn't like it, they can move to Arkansas.)But it's not up to me.And it's not up to you.Because we can all infect each other, it's only fair that we all get to decide.Vaccine regulation is democracy's job.And people are furious because they don't live in a democracy.Let's be honest about what this is really all about:This is allabout trust.People don't trust Big Pharma.Nor should they — if it were up to them, we'd all die unless we could pay top “free”-market dollar for their wares. They already do this in unregulated nations in Africa.People don't trust Big Medicine.Nor should they — the American for-profit healthcare system is the biggest scam in global health.People don't trust Big Government.Nor should they — we live in an undemocratic corporatocracy ruled by private interests with anti-commons agendas.But this has nothing to do with vaccine therapy.We need to think clearly about the big picture: We're rapidly approaching the age of the panopticon surveillance state.So long as we continue to buy from giant corporations and vote for their corporate-captured political parties and candidates, social credit systems are coming, with or without a vaccine passport.Regardless of mandates or economics or passports, I would've gotten the Covid vaccine anyway. Why? Because I believe in vaccination therapy's ability to help train my immune system to be awesome, and because this vaccine is proven to significantly decrease my chance of death by Covid.That's it.Vaccines just aren't political for me, at all. I can't fathom why anyone makes them political — vaccines are medicine that trains your body to fight pathogens, pure and simple. Sadly, ours is an age of outrageous conflation.Rather than thinking clearly and tackling the real problems of tyranny, we endanger our children because we think it's magically “creating change.”My track record shows that I'm extremely anti-partisan, anti-politician, and anti-corporatocracy, and I'm not going to let any tyrannical institution weaponize my own health against me.You shouldn't either.We need to stay strong so we can take them down. Get full access to Surviving Tomorrow at www.surviving-tomorrow.com/subscribe

The TWiV team notes the passing of Tom Steitz, an outbreak of acute flaccid myelitis in the US, a continuing Ebola virus outbreak in DRC, respiratory vaccinia due to inhalation of ground up rabbit skin, and how a human papillomavirus capsid protein directs virus-containing endosomes towards the nucleus. Hosts: Vincent Racaniello, Dickson Despommier, Alan Dove, Kathy Spindler, and Brianne Barker Subscribe (free): iTunes, Google Podcasts, RSS, email Become a patron of TWiV! Links for this episode Sea Phages program and application materials Tom Steitz, 78 (NY Times) AFM outbreak, US (CIDRAP) AFM surveillance (CDC) Acute Flaccid Paralysis and Enteroviral Infections (Curr Inf Dis Rep) EV-D68 neurotropism (bioRxiv) Ebola virus outbreakcontinues in DRC (CIDRAP) Vaccinia virus respiratory infection (Int J Inf Dis) HPV L2 penetrates endosome, brings virus retro (Cell) Letters read on TWiV 515 Timestamps by Jolene. Thanks! Weekly Science Picks Brianne - Germ City-Microbes and the Metropolis Museum Exhibition Alan- Nikon 2018 Small World in Motion competition Kathy- Ion Torrent Sequencing (video) Dickson- 2018 Nobel Prizes Economics Kathy- Ocean-centric map Vincent - Intelligence Matters Podcast: Anthony Fauci on threats from epidemics Listener Picks Gonsalo - Cells at Work (Manga, Anime) Intro music is by Ronald Jenkees. Send your virology questions and comments to twiv@microbe.tv

The TWiV team discuss the biology of Ebola viruses, and how localization of the membrane proteins of vaccinia virus drive function: the fusion machinery sits at the tips of virions, and binding proteins are at the sides. Hosts: Vincent Racaniello, Dickson Despommier, Alan Dove, Rich Condit, Kathy Spindler, and Brianne Barker Become a patron of TWiV! Links for this episode Support Viruses & Cells Gordon Conference Outbreak at the Smithsonian Outbreak (TWiV 501) Latest Ebola virus outbreak, DRC (WHO) Summary of Ebola virus outbreaks (CDC) Ebola virus nomenclature (ICTV) Ebola virus distribution map (CDC) Polarization of vaccinia virus membrane proteins (bioRxiv) Image credit Letters read on TWiV 507 Weekly Science Picks Alan - Puzzled Escape Games Rich - An Extremely Detailed Map of the 2016 Election Dickson - Parker Solar ProbeKathy - Ancient earth globe and connected Dinosaur database Brianne - STEMM education should get HACD Vincent - Free tuition for all NYU medical students Listener Pick Heather- GoFarm blog Intro music is by Ronald Jenkees. Send your virology questions and comments to twiv@microbe.tv

080 | Pursuing cures and advancing innovation   Welcome to another episode of Biotechnology Focus radio! I am your host – Michelle Currie – here to give you the rundown on what’s been happening on Canada’s biotech scene. It has been a busy last couple of weeks as the new genomics cloud platform was launched, a researcher from Roche Canada shares her input on future of innovation in cancer care, and the fight against cancer innovation trust invests almost half a mil in Ontario research technologies.   +++++  The world is opening up to the idea of genome sequencing. What was once a far-fetched idea is now beginning to materialize – and we are only at the tip of the iceberg. Information technology like Facebook, Google, Wikipedia and Uber are all prime examples of impactful software platforms that connect people with data that have set the stage for the next act.  When you look at where DNA sequencing began back in the 1970’s with the “Sanger sequencing method” as a process of determining the order of bases in the length of DNA, we’ve come a long way. But still, researchers are at the forefront of this revolution of gathering our personalized genetic information and using it to power the next generation of safer and more effective “precision” medicines.  This is where Marc Fiume and his team from DNAstack, a Toronto-based cloud genomics company, have their role to play. Started in 2014, the company began work with some exciting researchers from around Canada whose hot topics included autism and cancer research. But constantly they were told that the researchers just didn’t have enough samples to make sense of all the data they were collecting and that they really needed a platform that would connect them with other researchers globally who found themselves in the same position. Inspired by the concept of Facebook, they decided to build their own platform where genetic research could transpire among researchers worldwide.  He refers to the lack of data access as “potentially keeping life-saving information in a basement server room” and is one of his biggest frustrations when it comes to genomic research. Unveiling the sequence of a genome is challenging, time-consuming and expensive. Perhaps that is the reason why such a platform can no longer be just a notion, but become a mandatory tool so we can further our knowledge unified, instead of trying to connect the dots apart.  Genome sequencing is a lot like “decoding” of a foreign script or ciphering out a code of each individual’s personal genome. It is a long string of letters that forms a sort of molecular blueprint that is unique for each of us. These “strings” of letters are about six billion long, and currently, researchers are only grasping about a very small per cent of what those letters represent. This is why the need for sharing information should be a necessity.  In an attempt to break this societal self-inflicted mold, Marc worked with Dr. Stephen Scherer from The Centre of Applied Genomics on the “Personal Genome Project Canada” to facilitate the publication of health and genome records online for free. The intention being that whether you are sick or healthy, it is incredibly useful personally and for the research community to have your genome sequenced. Perhaps you have a predisposition to a potentially harmful genetic disease that you were not aware of before and could catch it before it starts, or if you are a carrier, or if you simply want to learn more about your ancestry. All of this is possible with genome sequencing. While some may not be ready to have theirs published online, it could still be made available to you in the privacy of your own home.  Marc and Ryan Cook, the other co-founder of DNAstack, have both tried to decrease the unease attached to publicly airing one’s genome sequence by publishing their own. “It’s about empowering and making key decisions about their healthcare in a way that’s not scary and also to break down barriers about data sharing,” comments Marc.  There are now 56 genome researchers that are bearing it all for the world to see, and encouragingly are following up on some of the data that they have found.  DNAstack recently launched their Canadian Genomics Cloud platform that is designed to better connect data, researchers and systems across the country to accelerate genomic discoveries and the implementation of precision medicine. It was invented by Canadian leaders with decades of experience in genomics, sequencing, cloud computing, software, security, and policy to democratize access to best-in-class infrastructure while respecting the unique national and provincial requirements for data privacy and security. Their aim is to service the needs of Canadian genome scientists from research institutions, clinical laboratories, pharmaceutical companies, hospitals, and industry.  The hope is to demonstrate that Canada now does have the capacity to do a precision medicine initiative at scale. Canada is really ready for this.” – says Marc.   +++++  For most of us, the start of a new year is a natural time to reflect on our progress as individuals. We take stock of the lives we’ve lived, the advances we’ve made, the impact we’ve had on those around us and the steps we need to take in the year ahead to achieve our goals.   For the Pharmaceutical and Biotechnology industry, the start of the new year is much the same. Standing at the doorstep of 2018, many of us who have spent our lives trying to advance healthcare around the globe believe that we are at a point in our careers, where science is progressing at a rapid rate.  In fact, some of us would venture that science is progressing at a rate that is outpacing our ability – as healthcare providers, as governments, as payers and as hospital institutions – to integrate these cutting-edge advances into clinical practice. While this reality poses significant challenges, it’s exciting to be on the threshold of so many unprecedented discoveries and novel treatment approaches for some of the world’s most devastating diseases.  The field of biotechnology is rich with discoveries that will have a dramatic impact on Canadians in 2018 and beyond. However, there are three key developments in the area of oncology in which we can expect to see some of the most transformative and immediate changes. These include:  the expanded role of diagnostics to optimize treatment choice;  the adoption of histology-agnostic treatment approaches; and  the next phase of true precision medicine     Expanded Role of Diagnostics  In recent years, the use of diagnostic tests within the Canadian cancer care setting has become an increasingly important practice, particularly for guiding treatment decisions and optimizing the patient’s chances for positive outcomes. In fact, it’s estimated that nearly 70 per cent of all treatment decisions today involve a pathology and/or laboratory investigation.  While the role of predictive biomarker testing has already been well established for some time in certain tumour types (such as HER2 in breast cancer or EGFR and ALK in lung cancer) we are witnessing the emergence of two trends that could further enhance patients’ care and their experience with our healthcare system. These include the ability to simultaneously look beyond a single biomarker through genomic profiling, and the viability of liquid/blood-based biomarker testing.  In 2018 we can expect to see a continued shift among healthcare providers to rely more on comprehensive genomic profiling to map each patient’s unique genomic profile to identify alterations across hundreds of genes known to be relevant in the development and progression of cancer. This broad approach optimizes the use of the available tumour tissue and provides physicians with the most comprehensive information to help guide their treatment selection. There is particular value in this approach for patients who have exhausted all standard treatment options or for those with rare forms of cancer with limited known effective treatment options.  Canadian institutions, like the British Columbia Cancer Agency, University Health Network in Toronto and The Jewish General Hospital in Montreal among many others, have already begun to demonstrate international leadership in this area with their in-house testing platforms and world-class genomic research programs.  We are also seeing the emergence of third-party molecular information providers, such as Foundation Medicine Inc., an organization that has partnered with Roche to offer genomic tests to provide physicians with information about a tumour’s unique genomic profile based on an interrogation of over 300 genes. These external services provide options for institutions that may not have the internal capabilities to offer such testing services and for patients who are looking for more comprehensive diagnostic information. All of these efforts are striving to rapidly expand treatment options by matching patients with approved targeted therapies, immunotherapies, and clinical trials based on their tumour’s molecular profile.  The second emerging trend in the space of predictive biomarkers is blood-based testing, which offers physicians a less-invasive testing mechanism for cases, in which there is insufficient tissue available for analysis. This may also prove to be a better option when a traditional tissue biopsy is not feasible due to tumour location, when a patient is in poor health, or when a physician and/or patient simply prefer a non-surgical option. In addition to supporting initial treatment choice, blood-based testing may also offer physicians the potential for continued monitoring in the future, resulting in earlier detection of disease progression and an assessment of resistance mutations to inform subsequent lines of therapy.     A Change in Mindset  Further to the evolution of diagnostic technologies, the increasing prevalence of targeted medicines is fundamentally challenging the way cancer research is conducted.  We are no longer seeing only large randomized Phase III studies measuring overall survival for drug development, but more novel trial designs, including basket and umbrella studies, as well as smaller Phase II designs to measure the safety and efficacy of a drug.  These new study approaches are aimed to accelerate scientific advancement and are addressing the challenges that exist when the prevalence of a particular molecular alteration is so limited that traditional trials seeking a large bolus of patients simply aren’t feasible.  In a basket trial, the impact of a single treatment across a spectrum of tumour types harbouring a particular alteration can be investigated. In contrast, umbrella trials inverse the approach, where multiple treatments are studied in patients with a common tumour type but who are stratified by molecular subtype.  Close to home, the Canadian Profiling and Targeted Agent Utilization (CAPTUR) trial sponsored by the Canadian Clinical Trials Group in partnership with several pharmaceutical companies and academic institutions across the country is a combined basket/umbrella study enrolling patients of all cancer types who are stratified into different arms of the study to receive treatments based on the genomic profile of their tumours.  Studies like CAPTUR will fundamentally shift how physicians view cancer, forcing them to look less at the type of cancer (e.g., breast, lung, colorectal) and focus on the molecular structure of the tumour.  This histology-agnostic approach is one that is also gaining traction with regulatory authorities around the globe. In fact, the U.S. Food and Drug Administration (FDA) recently approved a PD-1 inhibitor to treat patients with any cancer type, provided their tumours were unresectable or metastatic and classified as microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR).  This approval represented a significant departure from the traditional evidence requirements expected from a regulatory body and opens the door for further discussions and opportunities in other countries.  The final development, which seems like a natural extension of our evolving mindset around the use of diagnostics and targeted medicines in oncology is our view regarding how medicines can be engineered to offer truly individualized treatments to patients.  Though personalized medicines and immunotherapies are no longer considered ‘new’ in the rapidly evolving clinical landscape, the emergence of two types of truly bespoke cancer therapies marry these concepts to create what many consider a bold step in our quest to cure cancer.  Recently, two chimeric antigen receptor (CAR) T-cell therapies were approved in the United States, ushering in the next wave of personalized cancer care. These therapies involve the genetic engineering and reinfusion of a patient’s own T-cells to fight their unique cancers.  While approved in specific hematologic cancers today, researchers are also exploring these therapies in many solid tumours and the hope remains that they will offer a whole new way to think of treatment in cancer.  Still in its infancy, the second area of significant research is personalized cancer vaccines developed and manufactured for an individual patient based on the molecular profile of their tumours. Where off-the-shelf cancer vaccines have failed in the past, there is hope that these custom, uniquely tailored vaccines, in combination with checkpoint inhibitor therapies will succeed in transforming cancer care.  Close  In closing, while it’s easy to become discouraged by the often necessary hurdles required to integrate transformative products into current clinical practice, there has never been a more exciting time for those of who have built a career in the biotechnology industry; and there has never been a more exciting time for those of who have waited for a cure to cancer – a disease that has ravaged many of our families and has taken many of our friends and loved ones.  The reality is that science will continue to outpace clinical practice. But the promise of these discoveries can be realized if we – as stakeholders within the healthcare system – are willing and open-minded to collaborate on solutions, especially as we look at the impact personalized medicines can have in therapeutic areas beyond oncology, offering meaningful solutions to an infinitely greater number of patients, enabling them to live longer, healthier lives.  +++++  The fight against cancer innovation trust announces four new recipients of funding through its prospects oncology investment competition. Those recipients are Dalriada Therapeutics Inc., 16-Bit Inc., a cancer biomarker study at the Ontario Institute for Cancer Research (OICR), and a virus-based therapeutic under development at the Ottawa Hospital and the University of Ottawa.  FACIT’s investments are imperative in bridging the capital gap often experienced by early-stage Ontario companies, helping corporations establish jobs and build roots in the province. The wide-ranging scope of the innovations, which span therapeutics, machine learning and biomarker development, reflect the rich talent pool within the Ontario oncology research community.  Dalriada is a Canadian start-up founded with a mission to develop small molecule-based therapeutic technologies to battle diseases for which current treatment strategies are suboptimal or non-existent. With broad expertise in drug discovery, their efforts are currently centred on the preclinical development of a novel class (DT1) of small molecule inhibitors in cancers of the blood and brain as well as the development of a natural product for topical treatment of psoriasis and other inflammatory skin disorders.  16-Bit, a start-up founded by two medical doctors from the University of Toronto’s Diagnostic Radiology Program, is developing a machine learning algorithm to automate triaging of screening mammograms for breast cancer detection. Their focus is to utilize modern developments in machine intelligence to improve the accuracy, reliability, and speed of medical image interpretation while decreasing cost and barriers to healthcare.  Diagnostics Development Program at OICR leader Dr. John Bartlett has developed a diagnostic gene test to predict which breast cancer patients can benefit from anthracycline chemotherapy and which patients can avoid the associated toxicity because the drug may not be effective against their cancer.  The Ottawa Hospital and the University of Ottawa have developed a tumour-destroying virus based on the Vaccinia virus which adds a micro-RNA payload to enhance cell killing against pancreatic cancer. This targeted therapy is expected to be more precise and less toxic than conventional therapies for this difficult-to-treat tumour.  The Prospects Oncology Fund delivers on FACIT and OICR’s shared vision of advancing breakthrough innovations to the benefit of patients and Ontario’s knowledge economy.  Translating early-stage innovations and positioning them to raise additional funding supports Ontario’s competitive position as a destination for biotechnology.  Congratulations to all the strong applicants and in particular these outstanding awardees in their quest to make a difference for patients living with cancer.  +++++  Well, that wraps up another episode of Biotechnology Focus radio. I hope you enjoyed it. If you have a story idea or would like to be on the show, please email me at press@promotivemedia.ca. To see the articles in full check out the website biotechnologyfocus.ca and laboratoryfocus.ca so you don’t miss a beat! Have a momentous week. From my desk to yours – this is Michelle Currie.      

The TWiV team explains how infectious horsepox virus - likely the ancestor of smallpox vaccines - was recovered from chemically synthesized DNA fragments. Hosts: Vincent Racaniello, Dickson Despommier, Alan Dove, Rich Condit, and Kathy Spindler Become a patron of TWiV! Links for this episode ASV 2018: asv.org, asv2018.umd.edu Potential Zika virus related birth defects, USA (MMWR) Bordering on an outbreak (Tex Obs) Horsepox virus from synthesized DNA (PLoS One) Horsepox based smallpox vaccine (NEJM) Has horsepox become extinct? (Vet Rec) Evolutionary path of smallpox vaccines (Lancet Inf Dis) Equination (Vaccine) Image credit Letters read on TWiV 478 Weekly Science Picks Kathy - UM EEB photo contest Rich - Dino-Lite digital microscope and digital microscope camera Dickson - Sandford Photography Alan - A list of female virologists Vincent - Virology Lectures 2018 Listener Picks Andrew - Interferome Neva - The Untreatable by Gavin Francis Intro music is by Ronald Jenkees. Send your virology questions and comments to twiv@microbe.tv

Nels joins the TWiV team to talk about his work on genomic accordions in vaccinia virus, hepatitis B virus in a 439 year old mummy, and viral induction of energy synthesis by a long noncoding RNA. Hosts: Vincent Racaniello, Dickson Despommier, Alan Dove, Rich Condit, and Kathy Spindler Guest: Nels Elde Click arrow to play Download TWiV 476 (63 MB .mp3, 105 min) Subscribe (free): iTunes, RSS, email Become a patron of TWiV! Links for this episode ASV 2018: asv.org, asv2018.umd.edu TWiV is a must-listen (WaPo) More on poxvirus accordions (bioRxiv) HBV from a 439 year old mummy (PLoS Path) lncRNA promotes viral replication by inducing metabolism (Science) Making Data Visual Letters read on TWiV 476 Weekly Science Picks Nels - Everyday Evolution Kathy - Paper-fold an ellipse Rich - Oxford Nanopore Technologies: YouTube channel; General technology; DNA sequencing; Sequencing singularity Dickson - Spiders that look like pelicans Alan - Guessing pool for China Spacelab reentry Vincent - How to take a picture of the stealth bomber over the rose bowl Listener Picks Gretchen - The Bearded Lady Project Intro music is by Ronald Jenkees. Send your virology questions and comments to twiv@microbe.tv

Rich Condit joins Nels and Vincent to explain how a vaccinia virus protein customizes ribosomes to favor the translation of viral mRNAs with a stretch of A residues in the 5'-untranslated region. Hosts: Nels Elde and Vincent Racaniello   Become a patron of TWiEVO Rich Condit with Harry Noller (scroll down) Trans-Kingdom mimicry? (Nature) More on RACK1 (Nat Struct Mol Biol) Image credit Letters read on TWiEVO 21 This episode is brought to you by Blue Apron. Blue Apron is the #1 fresh ingredient and recipe delivery service in the country. See what’s on the menu this week and get your first 3 meals free with your first purchase – WITH FREE SHIPPING – by going to blueapron.com/twie. Science Picks Rich - Sniffing out significant “Pee values” Nels - Cuttlefish mimicking a hermit crab (evolutionary context) Vincent - Our first bioRxiv submission! Music on TWiEVO is performed by Trampled by Turtles Send your evolution questions and comments to twievo@microbe.tv

Avian Influenza (AI) viruses pose a threat to human and animal health and are responsible for potential economic losses. From the waterfowl reservoir, these RNA viruses can be transmitted to domestic poultry and humans, causing illness and death among people as well as mass culling of farm birds worldwide. This study contributes to increasing the knowledge by evaluating a promising poxvirus-based vector vaccine that carries and expresses an artificial, computationally derived hemagglutinin sequence in order to induce immunity against low pathogenic avian influenza H9N2. Modified Vaccinia virus Ankara (MVA) based vaccines have been tested in multiple human and animal trials and proved to be a safe and reliable vector system. The ancestral strategy uses a hemagglutinin sequence located at the node of a phylogenetic tree which arranges virus strains according to their evolutionary relationship. Inactivated whole virus vaccines engineered this way have conferred cross-clade protection in the ferret model of influenza A virus infections. In the present study, we aimed at testing the ancestral H9N2 MVA vaccine in the chicken model. Hereby, we tried to find answers to the following questions: What levels of H9 specific antibody responses are induced in chicken? Do the antibodies elicited by the ancestral H9 antigen cross-react with H9 antigens from other virus strains? Do the induced antibodies confer protection?

Hosts: Vincent Racaniello, Dickson Despommier, Alan Dove, Rich Condit, and Kathy Spindler The TWiV team reviews identification of immune biomarkers in CFS/ME patients, and how a cell nuclease controls the innate immune response to vaccinia virus infection. Links for this episode Immune signatures in ME/CFS (Science Adv) 11:15 Systemic exertion intolerance disease (Lancet) 19:50 Cell nuclease controls anti-viral responses (Cell Host Micr) 25:10 Poxvirus decapping enzymes prevent innate responses (Cell Host Micr) 1:15:40 Caps off to poxviruses (Cell Host Micr) Drummer Mohr (YouTube) 1:24:05 Bornavirus in squirrel breeders (ProMedMail) 1:28:45 Principles of Microbial Diversity 5:30 Journal of Microbiology & Biology Education 1:24:25 Cross-stitch by Anne Marie 1:34:40 Letters read on TWiV 329 1:25:00 Timestamps by Jennifer. Thank you! Weekly Science Picks 1:35:10 Alan - NASA Solar Dynamics Observatory videoRich - Mutagenic chain reaction (Video: Genome editing with CRISPR)Kathy - Science Ambassadors ProgramDickson - Street ArtVincent - End Polio Now Listener Pick of the Week Ross - Three PhD Comics on Nature vs Science (one, two, three)Ricardo - Demographic Party Trick Send your virology questions and comments (email or mp3 file) to twiv@twiv.tv

Sat, 31 Jan 2015 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/19149/ https://edoc.ub.uni-muenchen.de/19149/1/Torres_Dominguez_Lino_Ernesto.pdf Torres Dominguez, Lino Ernesto ddc:590, ddc:

Sat, 12 Jul 2014 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/17246/ https://edoc.ub.uni-muenchen.de/17246/1/Song_Fei.pdf Song, Fei

Hosts: Vincent Racaniello, Dickson Despommier, Rich Condit, and Kathy Spindler The TWiV team discusses how skin scarification promotes a nonspecific immune response, and whether remaining stocks of smallpox virus should be destroyed. Links for this episode Skin scarification protects against vaccinia virus disease (J Virol) Smallpox research agenda (PLoS Path) WHO report on variola research (pdf) Review of smallpox research program for WHO (pdf) How I record my lectures (virology blog) Letters read on TWiV 284 Weekly Science Picks Rich - EPCOTVincent - Medical BiotechnologyKathy - Alan Alda interview and Flame Challenge winnerDickson - NASA live from space Listener Pick of the Week Nicola - 50 cent microscope (be a beta tester)Jon - Camtasia Studio Send your virology questions and comments (email or mp3 file) to twiv@twiv.tv

Sat, 8 Feb 2014 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/17373/ https://edoc.ub.uni-muenchen.de/17373/1/Price_Philip.pdf Price, Philip John Ritchie ddc:590, ddc:500, Tierärztliche Fak

Background: Modified vaccinia virus Ankara (MVA) is a highly attenuated virus and a promising vaccine vector with potent immune stimulating properties. Deletion of the gene encoding the viral interleukin-1beta receptor (vIL-1 beta R) in MVA (MVA Delta IL-1 beta R) was previously shown to enhance memory T cell function. Here, we investigated the influence of vIL-1 beta R on blocking interleukin-1beta (IL-1 beta) upon MVA infection in various antigen presenting cells of murine and human origin, and analyzed whether inflammasome function contributes to IL-1 beta production in different cell types. Findings: Extending previous studies, immunizing mice with low doses of MVA Delta IL-1 beta R still showed enhanced memory CD8(+) T cell activation compared to MVA wild-type (MVAwt) immunization. In vitro, murine myeloid dendritic cells, and activated, but not naive primary macrophages were identified as potent producers of IL-1 beta upon infection with MVA. Importantly, free IL-1 beta was only detected in the absence of vIL-1 beta R. Moreover, MVA Delta IL-1 beta R increased amounts of bioactive IL-1 beta compared to MVAwt after infection of human THP-1 cells, as detected using a reporter system that only responds to active and free IL-1 beta. The MVA-mediated induction of IL-1 beta was confirmed to depend on inflammasome function in human and murine cells, however in murine cells this apparently involves caspase-1-independent pathways. Conclusions: MVA lacking IL-1 beta blocking activity leads to increased concentrations of free IL-1 beta upon infection of murine and human antigen presenting cells; this is likely responsible for enhanced memory T cell activation upon MVA Delta IL-1 beta R immunization of mice. Moreover, our results suggest that MVA-mediated IL-1 beta induction is a multifactorial process.

Hosts: Vincent Racaniello, Rich Condit, and Mark Challberg Vincent and Rich meet up with Mark Challberg to talk about his scientific career studying viral DNA replication, and his transition to an NIH Program Officer. Subscribe to TWiV (free) in iTunes, at the Zune Marketplace, by the RSS feed, by email, or listen on your mobile device with the Microbeworld app. Links for this episode: Purification of vaccinia virus DNA polymerase (J Biol Chem) Adenovirus DNA replication in vitro (PNAS) Herpes simplex viral genes required for DNA synthesis (J Virol) Letters read on TWiV 203 Weekly Science Picks Rich - Mattel Hot Wheels Curiosity RoverVincent - Should H5N1 Moratorium End? Listener Pick of the Week Claudio - DIY lab equipment (Ars Technica) and DIY Bio Send your virology questions and comments (email or mp3 file) to twiv@twiv.tv. You can also post articles that you would like us to discuss at microbeworld.org and tag them with twiv.

Hosts: Vincent Racaniello, Alan Dove, Rich Condit, and Kathy Spindler Vincent, Alan, Rich, and Kathy review fatal avian influenza virus in harbor seals, and poxvirus deployment of genomic accordions to counter antiviral defenses. Links for this episode: Avian influenza virus in harbor seals (mBio) Poxvirus genomic accordions (mBio) Red Queen hypothesis (Wikipedia) TWiV on Facebook Letters read on TWiV 198 Weekly Science Picks Alan - Getting Better: 200 Years of MedicineRich - Khan AcademyKathy - Vi HartVincent - Tweet Keeper Listener Pick of the Week Diane - The Way We Fall by Megan CreweStephen - Amateur Micrography Send your virology questions and comments (email or mp3 file) to twiv@twiv.tv, or call them in to 908-312-0760. You can also post articles that you would like us to discuss at microbeworld.org and tag them with twiv.

Hosts: Vincent Racaniello, Matthew Daugherty, Jondavid deJong, Helen Lazear, Stefan Oliver, and Cara Pager. Vincent returns to Madison, Wisconsin and meets with postdocs to discuss their science and their careers. Subscribe to TWiV (free) in iTunes , at the Zune Marketplace, by the RSS feed, by email, or listen on your mobile device with the Microbeworld app. Links for this episode: TWiV 189: Five postdocs in Glasgow ASM at the USA Science and Engineering Festival ASV 2012 at Madison, WI Photographs of ASV 2012 TWiV on Facebook Send your virology questions and comments (email or mp3 file) to twiv@twiv.tv, or call them in to 908-312-0760. You can also post articles that you would like us to discuss at microbeworld.org and tag them with twiv.

Hosts: Vincent Racaniello, Alan Dove, and Rich Condit Vincent, Alan, and Rich answer listener email about bioinformatics, insects, influenza, laboratory classes, commensalism, reproducibility of data, and more. Subscribe to TWiV (free) in iTunes , at the Zune Marketplace, by the RSS feed, by email, or listen on your mobile device with the Microbeworld app. Links for this episode: Vaccinia virus sequence from patient with vaccine complication (pdf) The evolution of intellectual freedom (thanks, Robin!) Free access to British scientific research (Guardian) xTAG respiratory viral panel Houston rabies case (Statesman) Tertulia (Wikipedia) TWiV on Facebook Letters read on TWiV 192 Weekly Science Picks Alan - The Microbial Olympics (supplementary information)Rich - PharmaJet needle free injection systemVincent - Microbes and Evolution by Roberto Kolter and Stanley Maloy (paperback and Kindle) Listener Pick of the Week Varun - Agile Gene by Matt RidleySizun - Plague IncRicardo - TED-EDKristopher - Ed Yong on Econtalk Send your virology questions and comments (email or mp3 file) to twiv@twiv.tv, or call them in to 908-312-0760. You can also post articles that you would like us to discuss at microbeworld.org and tag them with twiv.

Immune-manipulating parasites, bacterial genomes married to disease processes and viruses that bounce off already-infected cells make for an infectious episode of the Naked Scientists this week. Also up for analysis, why the eyes vote no to long space journeys; the problem with prostate cancer prediction; why nanoparticles trigger bacteria to breed superbugs and the contagious question of which cancers you can catch... Like this podcast? Please help us by supporting the Naked Scientists

Immune-manipulating parasites, bacterial genomes married to disease processes and viruses that bounce off already-infected cells make for an infectious episode of the Naked Scientists this week. Also up for analysis, why the eyes vote no to long space journeys; the problem with prostate cancer prediction; why nanoparticles trigger bacteria to breed superbugs and the contagious question of which cancers you can catch... Like this podcast? Please help us by supporting the Naked Scientists

Sun, 1 Jan 2012 12:00:00 +0100 https://epub.ub.uni-muenchen.de/23455/1/1742-4690-9-S2-P330.pdf Geldmacher, C.; Kroidl, A.; Hoelscher, M.; Biberfeld, G.; Sandstrom, E.; Wahren, B.; Lyamuya, E.; McCormack, S.; Joseph, S.; Robb, M.; Currier, J.; Bakari, M.; Aboud, S.; Mwakatima, M.; Lueer, C.; Maboko, L.; Kaluwa, B.; Missanga, M.; Mann, P.; Nilsson, C.; Sudi, L.; Haule, A.; Podola, L.; Bauer, A.

Vincent, Alan, and Rich discuss growth in culture of newly identified rhinovirus C, vaccinia transmission among wrestlers and martial artists, and results of phase III clinical trial of boceprevir, a new inhibitor of hepatitis C virus replication.

Vincent, Alan, and Rich answer listener questions about vaccinia virus, fungal viruses, synthetic viruses, influenza vaccine, HeLa cells, multiplicity of infection, and much more.

On episode #95 of the podcast This Week in Virology, Vincent, Dickson, Alan, and Rich consider the end of the influenza H1N1 pandemic, dengue in Florida, vaccinia virus infection in Brazilian monkeys, and viruses in the faecal microbiota. Host links Vincent Racaniello, Dickson Despommier, Alan Dove, and Rich Condit Links for this episode: WHO declares end of influenza H1N1 pandemic CDC's FluView WHO global monitoring of influenza Locally acquired dengue in Key West, Florida (MMWR) CDC page on dengue Vaccinia virus infection in monkeys of the Brazilian Amazon Dam site where animals were collected for vaccinia study (Google maps) Rich's article: Whence feral vaccinia? Viruses in the faecal microbiota of monozygotic twins and their Mothers (Nature) New Yorker article The Treatment (thanks, Jim!) Letters read on TWiV 95 Weekly science picks: Alan - Families Fighting Flu Rich - Food, Inc. Dickson -  Fuel Vincent - MIT Open Courseware Michael -  Waiting for Superman and Can Science Feed the World? (Nature)

On episode #90 of the podcast This Week in Virology, Vincent, Alan, Rich and Eric discuss identification of viruses in Northeastern American bats, vaccinia virus infection after sexual contact with a military vaccinee, and identification of a new flavivirus from an Old World bat in Bangladesh. Host links Vincent Racaniello, Alan Dove, Rich Condit, and Eric F. Donaldson Links for this episode: Vaccinia virus infection after sexual contact with vaccinee Smallpox vaccination overview Smallpox vaccine lesions (jpg) Smallpox hospital, Roosevelt Island, NY (photo 1, photo 2) Isolation of a flavivirus from bats in Bangladesh (PLoS Pathogens) Review on hepatitis G virus Dickson has been teaching at Singularity University and fishing in Bozeman MT (jpg) Letters read on TWiV 90 Weekly science picks: Eric - Year of Darwin by Sean Carroll Rich - March of the Penguins Alan - Standing-height desks Vincent - DengueWatch (thanks Richard!)

The WHO/UNAIDS “Global summary of the AIDS epidemic” released in December 2009, estimates that 33 million of people are living with HIV, 2.7 million were newly infected and 2.0 million of people died of AIDS in the last year. After more than two decades of research an effective preventive or therapeutic vaccine against HIV remains elusive and immunological correlates of protection remain unknown. T-cell mediated immunity is considered to play an important role in controlling HIV infection and progression to AIDS. Several candidate vaccines against HIV aiming to stimulate cellular immune responses are investigated in phase I to phase III clinical trials and assays enabling for a reliable, informative and sensitive measurement of CD4 and CD8 T-cell need to be implemented. Among the most promising vaccine candidates is recombinant modified vaccinia virus Ankara (MVA), a live viral vector system for the delivery of HIV-derived antigens. Several vaccination trials have made use of the modified vaccinia virus Ankara (MVA) as delivery vector. At present, the IFN-γ-based ELISPOT assay is considered as a gold standard and preferred primary assay in vaccine trials. However, despite its high sensitivity the measurement of the sole IFN-γ production provides limited information on the quality of the immune response. Polychromatic flow-cytometry-based assays as intracellular cytokine staining (ICS) offer the possibility to detect several markers on the same cell. Several findings from cross-sectional and longitudinal studies investigating different grades of HIV control highlight the importance of developing assays able to simultaneously measure several parameters on a single-cell level and strongly suggest the use of flow cytometry to monitor immune responses. In this work polychromatic flow-cytometry based assays were developed, optimized, and standardized for T-cell immunomonitoring purposes. In addition, these ICS based methods were compared with ELISPOT assays performed in two different experienced laboratories. The comparative study provided evidence that by the use of a special analysis system, the sensitivity of the ICS could be increased up to levels comparable to the sensitivity of the ELISPOT assay. The established polychromatic ICS together with a polychromatic CFSE-based proliferation assay were applied to a re-evaluation study of a vaccination trial using recombinant MVA expressing HIV-1-Nef (MVA-nef) in HIV-1 infected HAART treated individuals. In this study, the impact of the immunologic intervention with MVA-nef on the specific anti-Nef T-cell immune response was investigated in regard to cytokine production (IFN-γ and IL-2), chemokine production (MIP-1β), activation and differentiation marker expression (CD154 and CD45RA, respectively) and proliferative potential. Vaccine-induced polyfunctionality and proliferative capacity, which were associated with nonprogressive HIV-1 infection in several studies, were detectable by combining the two immune assays. By means of short-term ICS, a significant increase of polyfunctional Nef-specific CD4 T cells expressing IFN-γ, IL-2 and CD154 was observed following vaccination, whereas changes in the quality of the CD8 T-cell response could not be observed. Only the additional use of a long-term polychromatic CFSE-based proliferation assay revealed vaccine-induced Nef-specific CD8 as well as CD4 T cells with proliferative capacity. The correlation between the vaccine-induced IL-2 production by CD4 T cells and the increase of proliferating Nef-specific CD8 T cells suggests a causal link between these two functions. The insight gathered in this reevaluation study exceeded by far the information obtained in the original work using a simple IFN-γ-based immune assay. These results highlight the importance of combining sophisticated immunomonitoring tools to unravel concealed effects of immunologic interventions and support the use of the poxvirus-derived MVA vector to stimulate effective HIV-specific T-cell responses. From a technical point of view, these findings are important to guide the choice for suitable immune assays able to characterize the phenotype and function of specific T-cells in a highly sensitive way.

On episode #68 of the podcast This Week in Virology, Vincent, Alan, and Rich are enthralled by movies of vaccinia virus plaque formation, then consider how repulsion of superinfection virions leads to rapid virus spread, and a therapeutic prostate cancer vaccine. Host links Vincent Racaniello, Alan Dove, and Rich Condit Links for this episode: Rapid virus spread by repulsion of superinfection virions Movie of vaccinia virus plaque formation (.mov) Movie of GFP-vaccinia virus plaque formation (.mov) More amazing vaccinia virus movies Prostate cancer vaccine (Reuters article, original research) Weekly science picks: Rich Foundations of Virology - PowerPoint by Frederick A. Murphy (bio/interview pdf)Alan Spoonful of Medicine - Nature Medicine blog Vincent The Feynman Lectures (thanks Ilya!)

A TWiV panel of five considers the finding of Streptococcus pneumoniae in fatal H1N1 cases in Argentina, hysteria in the Ukraine over pandemic influenza, and human vaccinia infection after contact with a raccoon rabies vaccine bait. Host links Vincent Racaniello, Alan Dove, Rich Condit, Gustavo Palacios, and Mady Hornig Links for this episode: Argentine flu death mystery H1N1 influenza outbreak in Ukraine (article one and two, and WHO statement) Human vaccinia infection after contact with rabies vaccine bait Agrippal S1 inactivated H1N1 vaccine (pdf - thanks Ariel and Ayelet) Nick's letter on are viruses and life Take the poll: are viruses alive?

Vincent, Dick, Alan and Rich revisit a vaccinia virus lab accident and viral vaccines produced in plants, then talk about an iPhone app to track infectious diseases, flying foxes, and an inhaled measles vaccine. Links for this episode: Laboratory acquired vaccinia infection Medicago (investor presentation, pdf) and Fraunhofer produce vaccines in plants iPhone app Outbreaks near me No culling of flying foxes in Australia Inhaled powdered measles virus vaccine Herpesvirus latency confers symbiotic protection from bacterial infection (thanks Juliet!) Porcine circovirus vaccine Swine flu vaccine and Guillain-Barré (thanks Tom!) The Great Flu and blog post (thanks Swiss compass and Allison!) Building semiconductors with DNA (thanks Duncan!) Email on viral classification (thanks Rodney and Eliot!) Weekly Science Picks Rich Stumbling on Happiness by Daniel GilbertDick Eliot Porter at the Carter Museum and bookstore at AmazonAlan Dr. Clarke's H1N1 rap at the HHS sponsored YouTube contestVincent Coast to Coast Bio Podcast

Vincent and Dick discuss influenza virus-like particle vaccines produced in insect and plant cells, rapid sharing of influenza research, and answer listener questions about cytomegalovirus, viral evolution and symbiosis and much more. Links for this episode: A Farm on Every Floor Influenza virus-like particles in insect and plant cells PLoS Currents: Influenza Transmission of 2009 H1N1 influenza virus to turkeys [Thanks Debbie!] Baxter produces Vero cell H1N1 vaccine [Thanks Peter!] Boundaries of Darwinism podcast [Thanks David!] Phages in human intestine: papers one, two, three [Thanks Terry!] Post-exposure varicella vaccine [Thanks Patricia!] Open science movement here, here, here, and here [Thanks Jim!] Graduate programs in virology [Thanks Greggory and Blake!] Post-exposure Marburg and Ebola vaccines [Thanks John!] Vaccinia infection in the laboratory [Thanks Russ!] Animations of bacteriophage T4 life cycle [Thanks Jim!] Weekly Science Picks Vincent BionumbersDick Ocean: An Illustrated Atlas by Sylvia A. Earle, Linda K. Glover

In episode 34 of This Week in Virology, hosts Vincent Racaniello, Alan Dove, and guest Stephen Morse discuss progressive vaccinia in a smallpox vaccinee, arsenic and influenza in mice, facemasks and flu transmission, and antigenic and genetic analyses of the new H1N1 influenza virus. Links for this episode: Progressive vaccinia in a military smallpox vaccinee Arsenic compromises the immune response to influenza in mice Facemasks prevent flu transmission in a mathematical model Serum cross-reactive antibody response to the new H1N1 influenza virus Antigenic and genetic characteristics of the new H1N1 influenza viruses Preparation of influenza virus vaccine seeds Paul Ewald on the evolution of virulence Weekly Science Picks Alan Org-Mode Vincent Human/Swine A/H1N1 Influenza Origins and Evolution Stephen The Origin of Species by Charles Darwin

In episode 26 of This Week in Virology, hosts Vincent Racaniello, Alan Dove and guest Rich Condit converse about induction of polyomavirus replication in multiple sclerosis patients treated with the MS drug Tysabri, the extent of human polyomavirus infection, selection of influenza vaccines for the 2009-10 season, cowpox virus transmission from animals to humans, vaccinia-like virus infecting humans and cattle in Brasil, and poxviruses. Links for this episode: JC virus, Tysabri, PML, and mefloquine at virology blog Seroepidemiology of polyomaviruses in human Next season’s influenza virus vaccines and how they are selected Cell-culture propagated smallpox vaccine Cowpox tranmission from rats to humans ( Germany and France) and from cats to humans in Italy Vaccinia-like virus infecting cows and humans in Brasil When good vaccines go wild (review) Mosquito Map (thanks Duncan) Pfeiffer & Kirkegaard paper on quasispecies and virulence in mice Science blog of the week: Coevolvers by Devin Drown Science podcast pick of the week: QuackCast Science book of the week: Listen to the Music: The Life of Hilary Koprowski by Roger Vaughan

In episode 22 of This Week in Virology, host Vincent Racaniello and guest host Chris Upton, a professor in the Department of Biochemistry and Microbiology at the University of Victoria in Vancouver, Canada, converse about hepatitis B in India, AIDS gene therapy with a ribozyme, antibodies that neutralize many influenza virus strains, killing tumors with vaccinia virus, myxoma virus of rabbits, and the Viral Bioinformatics Resource Center. Links in the episode indlude: Hepatitis B outbreak in India AIDS gene therapy clinical trial Antibodies that neutralize many influenza virus strains (papers 1 and 2) Vaccinia virus as an oncolytic agent Mutations that attenuate myxoma virus in rabbits Viral Bioinformatics Resource Center Science blog of the week: The VBRC blog by Chris Upton Science podcast pick of the week: Nova ScienceNow Science book of the week: The Hot Zone by Richard Preston

Olá malta... Após um mês de Janeiro cheio de peripécias, consegui gravar uma nova edição do podcast. Desta feita, descrevo-vos um artigo onde se utiliza a estratégia de "prime-boost" amelhorada com CpG e FLT3L para aumentar a sua eficácia objectiva num ensaio pre-clinico em macacos para o virus SIV. O artigo chama-se "Adjuvanting a DNA vaccine with a TLR9 ligand plus Flt3 ligand results in enhanced cellular immunity against the simian immunodeficiency virus" publicado em 2007 no jornal JOURNAL EXPERIMENTAL MEDICINE. Eu achei este artigo muito interessante por ser um artigo relatando um ensaio pré-clinico em primatas (Rhesus macaques), e tratar-se de um modelo de HIV (human immudeficiency virus) - SIDA em português. É claro que neste experimental de primatas tenta-se tratar os animais com a variante símia (SIV). Outro factor interessante no artigo é o uso de uma estratégia de vacinação onde se utilizam dois vectores virais de origens distintas expressando os mesmo antigénios (SIV gag e pol) e HIV (Env e Nef). O uso de dois vectores distintos sequêncialmente chama-se prime-boost. O objectivo é evitar a neutralização do vector viral modificando a sua origem mantendo em comum o antigénio de interesse. Assim sendo o vector inicial é o virus Vaccinia e depois o vector seguinte é o virus Ankara. Os autores testam o ligando de Toll-like receptor9 (Desoxiribonucleotideos CpG) e o uso de Flt3 ligand para potenciar os efeitos da estratégia de prime-boost. Os autores descrevem que a vacina assim utilizada induz uma elevada mobilização de células dendriticas (células apresentadoras de antigénios profissionais do sistema imunológico) e em estado maturo de diferenciação. Como resultados os autores mostram que no grupo de animais tratado com Flt3L e CpG, o número de linfócitos T CD8 especificos do antigénio Gag do SIV é superior a todos os outros grupos animais testados, e que em termos clinicos a vacina tem efeitos profiláticos na protecção dos animais contra um infecção mucosal por via rectal com o virus SIV. Os dados apresentados são extremamente encorajadores para o uso desta estratégia prime-boost com CpG e Flt3L em estudos pré-clinicos em humanos. Dêem uma olhada e deixem os vossos comentários...

Modified Vaccinia Virus Ankara is a highly attenuated vaccinia virus strain developed during the smallpox eradication campaign. Nowadays recombinant attenuated poxviruses gain importance as live carrier vaccines against different infectious diseases and in cancer therapy. The aim of this work was to develop recombinant viral vectors, for presentation of a foreign antigen on the surface of extracellular enveloped particles (EEV). First, it was tested whether significant amounts of this viral form are produced by MVA in comparison to replication competent and widely used vaccinia virus strains. Using a number of independent approaches it could be shown that MVA infection in primary chicken embryo fibroblasts results in the production of enveloped viruses, but strikingly most of these were not released into the culture medium but remained attached to the plasma membrane. The results also showed that the replication competent vaccinia virus IHD-J is more efficient in trans-Golgi-network-wrapping and in releasing enveloped virions into the extracellular medium, while the WR strain is less efficient than MVA. Two different strategies were followed to target the recombinant protein to the surface of extracellular enveloped viruses. Since it was shown that non-vaccinia virus proteins can be incorporated to some extent into the outer membrane, a native model type II membrane protein was used. To increase the chance of foreign protein incorporation a fusion protein was used which consisted of the transmembrane domain of a protein known to be specific for the outer membrane of extracellular eveloped virus and the extracellular domain of the foreign antigen which was used in its native form. The data show that both proteins were incorporated into the extracellular enveloped virions produced in MVA infected chicken embryo fibroblasts, albeit with low efficiency. the ransmembrane domain of the EEV pecific protein was not sufficient to target the foreign protein specifically to the outer envelope.

The sequence of the gene encoding glycoprotein H (gH) of murine cytomegalovirus (MCMV) strain Smith was determined and compared with the sequence of the gH of MCMV strain K181. Transcriptional analysis showed that gH is encoded by a large mRNA of 5.0 kb, which is synthesized late in infection. A recombinant vaccinia virus expressing the MCMV gH open reading frame was constructed (Vac-gH). Anti-MCMV serum precipitated a protein of 87K from Vac-gH-infected cells. Reactivity with a monoclonal antibody showed the identity of the MCMV gH with a 87K envelope glycoprotein described previously by Loh and Qualtiere. Immunization of mice with the Vac-gH recombinant gave rise to an anti-gH serum, which neutralized MCMV without complement in vitro.

The gene encoding glycoprotein B (gB) of murine cytomegalovirus (MCMV) strain Smith was identified, sequenced, and expressed by recombinant vaccinia virus. The gB gene was found adjacent to the polymerase gene, as it is in the genome of human cytomegalovirus (HCMV). The open reading frame consists of 2,784 nucleotides capable of encoding a protein of 928 amino acids. Comparison with gB homologs of other herpesviruses revealed a high degree of homology. The similarity between the MCMV gB and the HCMV gB is most prominent, since 45% of the amino acids are identical. In addition, all cysteine residues are at homologous positions, indicating a similar tertiary structure of the two proteins. In contrast to HCMV, the MCMV gB mRNA is a true late transcript. A recombinant vaccinia virus expressing the MCMV gB gene has been constructed (Vac-gB). Antibodies raised against the Vac-gB recombinant precipitated proteins of 130, 105, and 52 kDa from MCMV-infected cells. The identity of the MCMV gB with the major envelope glycoprotein of MCMV described by Loh et al. was shown (L. C. Loh, N. Balachandran, and L. F. Qualtiere, Virology 166:206-216, 1988). Immunization of mice with the Vac-gB recombinant gave rise to neutralizing antibodies.

The nonstructural immediate-early protein pp89 of murine cytomegalovirus (MCMV) is the first viral protein synthesized after infection and has a regulatory function in viral gene expression. Despite its localization in the nucleus of infected cells, pp89 is also the dominant antigen recognized by MCMV-specific cytolytic T lymphocytes. The recombinant vaccinia virus MCMV-ieI-VAC, which expresses pp89, was used to study the capacity of this protein to induce protective immunity in BALB/c mice. Vaccination with MCMV-ieI-VAC induced a long-lasting immunity that protected mice against challenge with a lethal dose of MCMV but did not prevent infection and morbidity. In vivo depletion of CD8+ T lymphocytes before challenge completely abrogated the protective immunity. CD8+ T lymphocytes derived from MCMV-ieI-VAC-primed donors and adoptively transferred into sublethally irradiated and MCMV-infected recipients were found to limit viral replication in host tissues, whereas CD4+ T lymphocytes and pp89-specific antiserum had no protective effect. The data demonstrate for the first time that a single nonstructural viral protein can confer protection against a lethal cytolytic infection and that this immunity is entirely mediated by the CD8+ subpopulation of T lymphocytes.

The murine immediate-early (IE) protein pp89 is a nonstructural virus- encoded phosphoprotein residing in the nucleus of infected cells, where it acts as transcriptional activator. Frequency analysis has shown that in BALB/c mice the majority of virus-specific CTL recognize IE antigens. The present study was performed to assess whether pp89 causes membrane antigen expression detected by IE-specific CTL. Site-directed mutagenesis has been used to delete the introns from gene ieI, encoding pp89, for subsequent integration of the continuous coding sequence into the vaccinia virus genome. After infection with the vaccinia recombinant, the authentic pp89 was expressed in cells that became susceptible to lysis by an IE-specific CTL clone. Priming of mice with the vaccinia recombinant sensitized polyclonal CTL that recognized MCMV- infected cells and transfected cells expressing pp89. Thus, a herpesviral IE polypeptide with essential function in viral transcriptional regulation can also serve as a dominant antigen for the specific CTL response of the host.

Sat, 1 Jan 1977 12:00:00 +0100 https://epub.ub.uni-muenchen.de/6963/1/6963.pdf Thomssen, R.; Wekerle, H.; Ertl, H.; Koszinowski, Ulrich H.

Sat, 1 Jan 1977 12:00:00 +0100 https://epub.ub.uni-muenchen.de/6956/1/6956.pdf Koszinowski, Ulrich H.; Gerike, Rainer; Ertl, Hildegund

Vaccinia virus-infected cells were treated enzymatically to remove H-2 antigenic sites. The effect of this procedure on virus-specific cell-mediated cytolysis (CMC) and virus-specific antibody-mediated cytolysis (AMC) was tested. Due to the inhibition of cellular proteinsynthesis by the vaccinia virus infection, H-2 antigenic sites were not resynthesized while there was a continuous production of viral surface antigens. These cells with a high concentration of viral surface antigens and decreased H-2 determinants could be used as targets in the virus specific AMC. But they were not lysed in the virus specific CMC which emphasizes the significance of H-2 antigens during recognition of virus-specific determinants by T cells.

Infection of mice with the vaccinia virus strain WR, Elstree or DIs, a conditional lethal mutant of vaccinia virus, resulted in the generation of vaccinia virus-specific sensitized cytolytic T lymphocytes (CTL). It could be shown by cross-reactivity between the three strains and by inhibition experiments with specific antisera that early vaccinia surface antigens are sufficient for the generation of specific CTL in vivo and for the lysis of infected target cells in vitro.

The action of peritoneal exudate cells (PEC) from normal and vaccinia virus infected mice on infectious vaccinia virus particles was investigatedin vitro. PEC from immune mice showed a significantly higher infectivity titre reduction (virus clearance, VC) than normal cells. This effect could be clearly attributed to the macrophage. Vaccinia virus multiplied in PEC from normal animals while there was no virus propagation in cells from immunized mice. The release of adsorbed or engulfed virus was reduced significantly in PEC from immunized animals. Anti-vaccinia-antibodies seem to activate normal macrophages to increased virus clearance. This stimulating effect was demonstrable only in the IgG fraction of the antiserum. The activity of macrophages from mice injected three times over a period of 14 days with vaccinia virus could be entirely blocked with anti-mouse-IgG, while PEC from mice injected one time six days previously were not inhibited.

Cell mediated immunity to vaccinia virus in man was studied by lymphocyte transformation. Vaccinia antigen, propagated on BHK-21 and Vero cells, could be used successfully for in-vitro testing after partial purification as well as crude infectious homogenates. Vaccinia antigen preparations were effective both in the infective and the inactivated state. Inactivation was usually accompanied with a certain loss of stimulating activity. Development of cell mediated immune response in-vitro after first vaccination was investigated in 17 adults. Vaccinia virus specific lymphocyte transformation was seen in the second week after vaccination in all cases. Following revaccination no increase of lymphocyte transformation ratio could be observed in 11 persons studied. At the same time the titers of humoral antibodies were elevated.

VARIOUS virus infections lead to the formation of cytotoxic lymphocytes (CL), which are capable of killing virus-infected target cells1−4. Specific lysis of target cells infected with 51Cr-labelled vaccinia virus could be observed when investigating the cell-mediated cytotoxic reaction to vaccinia virus5; the CL could be characterised as a T cell. The sensitised lymphocytes from C3H mice could only kill syngeneic L929 cells infected with vaccinia virus, whereas lysis by sensitised lymphocytes derived from DBA/2 mice was restricted to the syngeneic infected mastocytoma P815X2 cells. In the lymphocytic choriomeningitis infection the target cell lysis was shown to be restricted by H-2 antigen6. We report here experiments with primary fibroblasts of the mouse strains C3H, DBA/2 and the (C3H DBA/2)F1 generation were designed to affirm that the effector phase of virus-specific lysis of target cells mediated by T cells is restricted by H-2 antigen even in the vaccinia virus infection. Further experiments with H-2 alloantisera were performed to indicate the close local relationship between H-2 antigens and viral surface antigens.

MICE generate cytotoxic T lymphocytes (CTL) which are able to lyse virus infected target cells in vitro after infection with lymphocytic choriomeningitis virus (LCMV) and pox-viruses1−3. CTL kill syngeneic and semiallogenic infected cells but not allogenic infected targets. Target cell lysis in these systems seems to be restricted by H-2 antigens, especially by the K or D end of the major histocompatibility complex (MHC). In experiments where virus specific sensitised lymphocytes kill virus infected allogenic target cells4 the effector lymphocytes have not been characterised exactly. Recent investigations suggest that the active cell in this assay, at least in the measles infection, is a non-thymus derived cell (H. Kreth, personal communication). An H-2 restriction of cell mediated cytolysis (CMC) to trinitrophenol (TNP)-modified lymphocytes has also been described5. Zinkernagel and Doherty6 postulated that the CTL is directed against syngeneic H-2 antigens and viral antigens and they suggested an alteration of H-2 induced by the LCMV infection. Earlier7 we found a close topological relationship between H-2 antigens and the target antigen(s) responsible for CMC in the vaccinia system. Here we report experiments which were carried out to prove alteration of H-2 after infection of L-929 fibroblasts with vaccinia virus.

Vaccinia virus specific cytotoxicity against infected target cells was observed in vitro. Spleen lymphocytes from normal and immunized mice of the inbred strains C3H and DBA/2 were incubated with vaccinia virus-infected and non-infected 51Cr-labeled mastocytoma P-815-X2 cells and L-929 fibroblasts, which were used as targets. Cytotoxic lymphocytes could be isolated from the mice as early as 2 days after infection with vaccinia virus. The highest cytotoxic effect was obtained with lymphocytes taken 6 days after infection. The degree of lysi was correlated with the ratio of immune lymphocytes to target cells. Specific blocking of target cell lysis resulted after addition of anti-vaccinia antibody from different sources. The effector cells could be characterized as T cells by elimination of macrophages and B cells. Target cell killing was only possible in a syngeneic system; allogeneic infected target cells were not lysed significantly.

Tue, 1 Jan 1974 12:00:00 +0100 https://epub.ub.uni-muenchen.de/6976/1/6976.pdf Koszinowski, Ulrich H.; Bandlow, G. ddc: