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  1. Biden moves up deadline for states to open COVID-19 vaccines to all adults The president wants all US adults to be eligible for a shot by April 19. Americans above the age of 16 will be eligible for a vaccine nationwide later this month. Sarah Tew/CNET President Joe Biden on Tuesday announced that he wants states to make all adults eligible for coronavirus vaccines by April 19, taking nearly two weeks off his previous May 1 deadline. "We aren't at the finish line. We still have a lot of work to do. We still are in a life-and-death race against this virus," Biden said during a White House briefing Tuesday afternoon. The Biden administration has been working to ramp up availability of COVID-19 vaccines, including increasing the number of pharmacies in the federal vaccine program from 17,000 to nearly 40,000 stores. The government is also working to open a dozen more federally run mass vaccinations sites. In March, Biden said the US was on track to have enough doses of COVID-19 vaccine for every adult in America by the end of May. In total, more than 167 million vaccines doses have been administered in the US, according to John Hopkins University, with over 48 million people being fully vaccinated. Three coronavirus vaccines have been rolled out in the US -- two-shot vaccines from Pfizer and Moderna as well as a one-shot vaccine from Johnson & Johnson -- after being authorized for emergency use by the Food and Drug Administration. Biden visited a vaccination site in Alexandria, Virginia, on Tuesday and later delivered remarks on the state of vaccinations during a briefing at the White House. Here's where to get a COVID-19 shot and how to track how many vaccines are available in your state. CNET reporter Corinne Reichert also contributed to this report. First published on April 6, 2021 at 6:58 a.m. PT. Source: Biden moves up deadline for states to open COVID-19 vaccines to all adults
  2. EU pressures AstraZeneca to deliver vaccines as promised European Council President Charles Michel, left, and European Commission President Ursula von der Leyen leave after a joint news conference at the end of a EU summit video conference at the European Council headquarters in Brussels, Thursday, Jan. 21, 2021. European Union leaders assessed more measures to counter the spread of coronavirus variants during a video summit Thursday as the bloc's top disease control official said urgent action was needed to stave off a new wave of hospitalizations and deaths. (Olivier Hoslet, Pool Photo via AP) BRUSSELS (AP) — The European Union lashed out Monday at the pharmaceutical giant AstraZeneca, accusing the company of failing to deliver the coronavirus vaccine doses that it promised to the bloc despite getting EU funding to ramp up vaccine production. The EU, already facing heavy criticism for a slow vaccine rollout around its 27 nations, also warned that within days it will demand approving the export of any COVID-19 vaccines produced within the bloc. “The European Union will take any action required to protect its citizens and its rights,” Health Commissioner Stella Kyriakides said. The EU, which has 450 million citizens and the economic and political clout of the world’s biggest trading bloc, is lagging badly behind countries like Israel and Britain in rolling out coronavirus vaccine shots for its health care workers and most vulnerable people. That’s despite having over 400,000 confirmed virus deaths since the pandemic began. Kyriakides immediately got the support from the bloc’s largest member on the vaccine export controls plan. “We, as the EU, must be able to know whether and what vaccines are being exported from the EU,” German Health Minister Jens Spahn said. “Only that way can we understand whether our EU contracts with the producers are being served fairly. An obligation to get approval for vaccine exports on the EU level makes sense.” European Commission President Ursula von der Leyen held urgent talks Monday with AstraZeneca chief Pascal Soriot, and EU nations also met with AstraZeneca to encourage the British-Swedish company to ramp up its vaccine production and meet its contractual targets. “The answers of the company have not been satisfactory so far,” said Kyriakides and added a follow-up meeting was planned late Monday. The European Medicines Agency is scheduled to review the Oxford-AstraZeneca coronavirus vaccine Friday and its approval is hotly anticipated. The AstraZeneca vaccine is already being used in Britain and has been approved for emergency use by half a dozen countries, including India, Pakistan, Argentina and Mexico. AstraZeneca’s announcement that it will deliver fewer vaccines to the EU early on has only increased pressure on the 27-nation bloc, especially since Pfizer-BioNTech, the first vaccine to get EU approval, failed last week to keep up its promised deliveries to the EU. Pfizer has temporarily reduced vaccine deliveries to the EU and Canada as it revamps its plant in Belgium to increase overall production. Italy has threatened to sue Pfizer for the delays. The political pressure spurred the European Commission, which is the EU’s executive, into action Monday, with von der Leyen’s phone call to the AstraZeneca chief. “She made it clear that she expects AstraZeneca to deliver on the contractual arrangements foreseen in the advance purchasing agreement,” said her spokesman Eric Mamer. “She reminded Mr. Soriot that the EU has invested significant amounts in the company up front precisely to ensure that production is ramped up even before the conditional market authorization is delivered by the European Medicines Agency.” The company said in a statement that Soriot “stressed the importance of working in partnership and how AstraZeneca is doing everything it can to bring its vaccine to millions of Europeans as soon as possible.” The delays will be make it harder to meet early targets in EU’s goal of vaccinating 70% of its adult population by late summer. European Council President Charles Michel said the EU already “pounded our fist on the table” with Pfizer last week to ensure that the delays end by the end of this week. The EU has signed six vaccine contracts for more than 2 billion doses, but only the Pfizer-BioNTech and Moderna vaccines have been approved for use so far. Source: EU pressures AstraZeneca to deliver vaccines as promised
  3. Who Discovered the First Vaccine? As the world scrambles to develop an inoculation against Covid-19, it’s worth understanding the early, extraordinary history of the technique. Edward Jenner using cowpox to inoculate a child against smallpox. He was improving on a technique used by Thomas Dimsdale almost 30 years previously to inoculate Catherine the Great.WELLCOME IMAGES/Science Source The English doctor Thomas Dimsdale was nervous. It was the evening of October 12, 1768, and Dimsdale was preparing the empress of Russia, Catherine the Great, for her procedure. From a technical perspective, what he planned was simple, medically sound, and minimally invasive. It required only two or three small slices into Catherine’s arm. Nevertheless, Dimsdale had good reason for his concern, because into those slices he would grind a few scabby pustules teeming with variola—the virus responsible for smallpox and the death of nearly a third of those who contracted it. Though he infected Catherine at her behest, Dimsdale was so concerned about the outcome that he secretly arranged for a stagecoach to rush him out of Saint Petersburg should his procedure go awry. What Dimsdale planned is alternatively called a variolation or inoculation, and while it was dangerous it nevertheless represented the pinnacle of medical achievement at the time. In a variolation, a doctor transferred smallpox pustules from a sick patient into a healthy one because—for reasons no one at the time understood—a variolated patient typically developed only a mild case of smallpox while still gaining lifelong immunity. Twenty-eight years later, Edward Jenner improved this proto-vaccination when he discovered he could use a safer, sister virus of variola called cowpox to inoculate his patients. But it’s the original variolation—not Jenner’s vaccine—that first established the efficacy of the crazy, and at the time ludicrously dangerous, idea upon which nearly all vaccines rely: the intentional infection of a healthy person with a weakened pathogen to bequeath immunity. Modern immunologists have advanced this life-saving concept to such a degree that if they find a vaccine for Covid-19, it will pose no risk of widespread infection. Inoculums today induce the production of antibodies while being incapable of large-scale reproduction. But that wasn’t the case when they were first discovered. When Dimsdale variolated Catherine, his process merely gave her immune system the upper hand. He knew she would sicken. By now we are so familiar with the lifesaving concept behind vaccines that it’s easy to forget how insane, genius, and unethical these first inoculations must have been. Even Dimsdale, who had performed the procedure thousands of times, was clearly skeptical that he could talk his way out of a noose should Catherine’s variolation end poorly. And yet the idea to intentionally infect a patient with a lethal virus to help them did first occur to someone—and it was perhaps the greatest idea in the history of medicine. It was not Jenner’s idea, nor was it Dimsdale’s. But it may have been a single person’s. Remarkably, variolation may not have been independently discovered. Instead, the earliest documentation suggests it began in China—probably in the southwestern provinces of either Anhui or Jiangxi—before spreading across the globe in a cascading series of introductions. Chinese sea merchants introduced the procedure to Africa, brought knowledge of it overland to India, and carried it along the Silk Road to Turkey, which is where 18th-century European ambassadors finally learned of the technique and brought it home. The timing and paths of variolation’s introductions around the world suggests that the idea spread out of one place, at one time. Perhaps from one person. According to one legend, recounted in Yü Thien-chhih’s Collected Commentaries on Smallpox, written in 1727, the first inoculator was “an eccentric and extraordinary man who had himself derived it from the alchemical adepts.” Who was this “eccentric and extraordinary man” who invented immunology with one of the greatest ideas and boldest experiments in medical history? His or her name is not only long lost, but it was probably never written. However, legends and ancient Chinese medical treatises make it possible to construct a plausible biography for someone who I’ll simply call the “extraordinary man,” after Thien-chhih’s legend, or “X” for short. X may have been a healer, a traveler, and someone who believed in practices outside the contemporary Chinese medical mainstream, according to the biochemist and historian Joseph Needham. By the time "he" (if we take Thien-chhih’s legend literally) practiced, mainstream Chinese medicine was soundly based on pharmacies, physical therapy, and rational techniques. But X existed on the edge of it, mixing mainstream medical methods with magic. He may have been what was referred to at the time as a fangshi, writes Chia-Feng Chang in Aspects of Smallpox and Its Significance in Chinese History. But fangshi is a word that in some ways defies translation, because comparative English words like exorcist or diviner bring to mind more nefarious individuals than he probably was. Instead, he was a traveling healer who, while certainly a believer in magic, also preached practical medical ideals such as hygiene and a healthy diet. X is unlikely to have received any formal medical training. Instead, he learned his secrets and practices from relatives or masters. He was probably illiterate, or nearly so, and thus learned and taught his techniques entirely through oral tradition. This partly explains why his name wasn’t lost so much as it was never recorded—but even if he could have documented his discoveries he is unlikely to have done so. Traditionally, fangshi like X kept their practices and methods secret to all but a few disciples. Variolation may have been what was called a chin fang—or “forbidden prescription,” writes Needham in Science and Civilization in China. Chin fang were “confidential remedies handed down from master to apprentice, sometimes sealed in blood.” In a way, X was not unlike a modern Western magician. His secrets were his livelihood. Revealing them might ruin the magic, but it would certainly hurt future business. The fangshi tradition of secrecy—along with the numerous legends surrounding inoculation—have sparked intensive scholarly debate about when exactly variolation began. The earliest written evidence of inoculation originates from mid-16th-century writing. A medical treatise written in 1549 titled On Measles and Smallpox by the physician Wan Chhüan describes “transplanting the smallpox” into healthy patients. But inoculation probably began at least a few generations before Chhüan’s mention of it, because he notes the practice may bring about menstruation. The knowledge of this fairly specific side-effect suggests healers had been practicing this procedure for some time. But exactly how much earlier is a matter of debate. If you take the legends surrounding variolation seriously, then the practice began as early as the 11th century. In one of the most popular accounts, documented in the Golden Mirror of Medical Orthodoxy, written in 1749, a hermit living on a sacred mountain in the Sichuan province of China invented variolation at the turn of the first millennium. According to this legend, the healer heeded the pleas of the prime minister Wang Tan and descended the mountain to save the minister’s family from smallpox. Yet many scholars are suspicious of this and similar tales. Why do no contemporary accounts exist of such a remarkable event as the inoculation of this prime minister? And why is there no evidence for more than 500 years of such a revolutionary and effective practice when there are numerous, far older written documents concerning the treatment of smallpox itself? The weight of the evidence, and sudden burst of documentation, suggest the practice first arose in the late 15th or early 16th century shortly before its appearance in medical texts. In all likelihood, X variolated his first patient around the same time Christopher Columbus landed in the New World. But rather than obfuscating the origin of variolation, the existence of the legends may themselves be evidence. If the first practitioners existed outside the medical mainstream, their first patients would have been deeply suspicious of the radical technique. They would have been justifiably reluctant to intentionally infect themselves or their children with variola. So, like any good traveling healer, the first practitioners concocted stories to add to the procedure’s credibility. These were “legends to justify its origin and function,” writes Chang. As any good salesman would know, one doesn’t sell their elixir by saying that they came up with the recipe. “Variolation took lots of effort and time to gain trust and support to become popular,” Chang writes to me. Part of this effort to gain trust involved myths of its invention. If a patient believed the mysterious remedy originated from an eccentric healer who lived on a sacred mountain centuries ago, they were more likely to try it. It wasn’t necessarily fraud. It was just good business. Yet even if the legends are true, and X lived thousands of years earlier than scholars believe, he still had to invent variolation. Unfortunately, just how exactly he did so is as lost as his name. “What made them try a thing as weird as variolation? Unfortunately, we don’t have a neat origin story like the one about Jenner,” Hilary Smith, author of Forgotten Disease: Illnesses Transformed in Chinese Medicine, writes to me in an email. But we do know many of the traditional Chinese medicines a healer like X would have practiced that, when combined with what he knew about smallpox, may have led him to his remarkable conclusion. Smallpox first entered China after general Ma Yüan’s campaigns to conquer what is now Vietnam in 42 CE, according to the third-century philosopher Ko Hung. In 340 CE, Hung wrote that Yüan’s army caught the disease while attacking the “marauders” and brought it home—which is why the Chinese called smallpox “the marauders pox.” (In nearly every language, the original term for smallpox is often some form of “the foreigner’s disease.”) The ensuing epidemic wracked China. Smallpox so comprehensively killed or immunized the population that as the centuries passed the average age of the infected person began to drop. By the year 1000, smallpox had so thoroughly ravished the country that children possessed the only naïve immune systems left to attack. Everyone else was either dead or immunized. The disease became so endemic that Chinese doctors viewed its contraction as an inevitability. They believed the disease was a passage all children would have to eventually cross, and called smallpox “the gate of humans or ghosts.” With a death rate of at least 30 percent, outbreaks produced tragic results. Over a single Beijing summer in 1763, variola killed more than 17,000 children. Smallpox’s inevitability, combined with its predilection for children, caused many to believe the disease was a kind of original sin. By the turn of the first millennium, doctors were convinced smallpox was caused by a kind of “fetal toxin” that, like puberty, would break out at some undefinable point in a child’s early years. In an attempt to remove this toxin, doctors performed extensive “filth and mouth cleanings” on newborns. At the same time, healers like X would have understood that the disease could be passed from human to human and couldn’t be caught twice. Those who hadn’t caught the disease (“raw bodies,” as the Manchus called them) fled when outbreaks occurred, and those who had survived (“cooked bodies”) cared for the sick. As early as 320 CE Hung wrote of smallpox, “He who knows it can pass safely through the worst epidemics, and even share a bed with a sick person, without himself being infected.” Understanding these two concepts are foundational to the principles of inoculation, but they were not unique to China. So perhaps X was aided by beliefs specific to traditional Chinese medicine. One ancient Chinese medical technique X may have practiced was called “yi tu kung tu” or “fighting poison with poison.” For centuries, medical healers in China had mixed teas of known poisons such as camptothecin and periwinkle to fight cancers, so the idea of using a lethal substance as a cure may not have been as foreign to X as it would have been in other cultures. Of course, there is a significant difference between poisonous teas prescribed to sick patients and administering a lethal pathogen to an entirely healthy person. And yet this, too, fell in line with Chinese traditional medicine, which focused heavily on preventative care as opposed to Western doctors’ emphasis at the time on reactive treatment. We may never know exactly what motivated or inspired the first inoculators, but if X was aware of person-to-person transmission, knew a person could only be infected once, knew a child would almost inevitably contract the disease naturally, believed in the efficacy of poisonous medications, and had a strong preference for preventative care—the stage was then set for a keen observation. Perhaps X watched siblings pass around a particularly mild case of smallpox and suggested to a pair of desperately concerned parents that rather than running from the inevitable, they fight poison with poison and guide their child through the gates of humans and ghosts with this apparently milder form. Or at least, that could be how X conceived of it. But like any good traveling diviner, this healer punched up his story to convince what must have been a pair of incredibly skeptical parents. The earliest variolation technique was to simply wear the used clothing of a smallpox infected patient, according to Needham. But X wouldn’t have simply handed his patient old clothes. Instead, early healers performed dramatic inoculations on auspicious dates. They lit incense, burned money, recited charms, and invited the gods and goddesses responsible for smallpox to protect the child. Then they handed them the clothes—and waited. If X’s first patient experienced a typical inoculation, then by the fifth day the child would have developed a fever and sprouted bulbous pocks of pus. But rather than the sheets of black pustules that develop in a lethal case, X’s patient would grow only a smattering of smaller and lighter-colored pox. As soon as X noted these smaller pox, they would have known the child would progress into only a mild case of the disease. They would have known that remarkably—stunningly—this reckless experiment had worked. The obvious question, of course, is why? Why did the child experience a mild case instead of a lethal one? Why is variolation a safer means of contracting smallpox? X certainly would have had an explanation, but it’s unlikely to have been correct. The actual answer is thanks to something epidemiologists call the dose-response curve. The dose-response curve is the relationship between the severity of one’s disease and the quantity of the initial dose. This is different from the “minimum infectious dose,” which measures the fewest virus particles you can receive before you’re likely to become infected. In variola the minimum infectious dose is somewhere around 50 viral particles—also called virions—which sounds like a lot, but 3 million could sit on the head of a pin. According to Rachael Jones, a professor of health and sciences at the University of Utah, a single virion could theoretically infect you, but it’s unlikely. According to her, an infectious dose of variola is a little like playing Russian roulette: More virions equal more bullets. But all things being equal, more virions also equal greater severity. And this is the relationship the dose-response curve attempts to chart. Unfortunately, dose-response is incredibly difficult to establish outside clinical settings. It’s nearly impossible to re-create the dose a person naturally received, so quantifying dose-response requires intentionally infecting a group of patients with a measured amount of a given pathogen. That’s problematic, particularly with dangerous infectious diseases like variola. Obviously, you cannot infect humans with increasing amounts of variola and measure their response, but a study on mice found there is likely a correlation between the virus’s infectious dose and severity. Small quantities of variola injected into mice left them mildly sick or asymptomatic, while the largest doses were universally fatal. It’s difficult to definitively establish dose-response curves, but the evidence suggests that the larger the infectious dose of variola, the worse a patient’s prognosis. Mark Nicas, a professor emeritus at UC Berkeley who researches pathogen exposure and risk assessment, tells me that a relationship between the size of the initial dose and the severity of your outcome is probably true for all pathogens. The dose-response curve of variola likely explains why X’s patient experienced a mild case, and why variolation worked. By choosing the clothes of a patient who came down with a mild case, X unknowingly took advantage of two basic principles of variola: First, patients with milder cases shed fewer virions in their pustules; second, as the clothes sat, many of those virions would have died. As a result, X’s patient would have been initially infected with a smaller dose than they would have been likely to contract naturally. The dose would have been sufficient to spark an infection and induce the production of antibodies but low enough to significantly reduce the risk of death. Variolation was a balancing act: Too potent a dose and the patient would contract a dangerous case; too little and they wouldn’t produce antibodies. As inoculators gained experience they refined the procedure to produce milder infections, but even the earliest inoculators report death rates of 2 to 3 percent, compared to the natural rate of 30 percent. The oldest instructions for variolation suggest selecting pustules from only the mildest smallpox cases and prescribe the proper method for storing and aging the scabs. Using these simple processes, inoculators unknowingly performed the earliest viral attenuations. By the time of Dimsdale’s procedure, fewer than 1 in 600 patients died from variolated smallpox. In the end, Dimsdale need not have been concerned. Catherine developed only a mild illness, and his getaway vehicle sat unused in her driveway. The variolation was so successful, Dimsdale later said he had to use a microscope to see the pustules that formed around her cut. In a letter to Voltaire, Catherine wrote “the mountain had given birth to a mouse” and that her era’s brand of anti-vaxxers were “truly blockheads, ignorant or just wicked.” Three decades after Catherine’s inoculation, Jenner discovered and popularized cowpox pustules as a replacement to smallpox’s. His procedure resulted in even safer inoculations, and Jenner named his method vaccination. When Louis Pasteur discovered he could attenuate and inoculate other pathogens such as anthrax and rabies—Jenner’s name stuck. Even as immunologists have evolved their techniques, the principle behind vaccines has largely remained the same since the magic-believing X first discovered it. It seems surprising that one of medicine’s most ingenious inspirations arose in someone who so loosely tied their beliefs to scientific-based medicine. As Needham writes, “It remains paradoxical that inoculation arose among the exorcists.” But perhaps the idea to intentionally infect someone with one of humanity’s deadliest infectious diseases was so outrageously dangerous that variolation could only have been conceived and popularized by someone outside the medical mainstream. Maybe it could only have been tried by an observant believer who could tell a great story. Who Discovered the First Vaccine?
  4. Researchers become their own lab rats with DIY coronavirus vaccine Antivirus: a weekly digest of the latest COVID-19 research A photo illustration showing vials of COVID-19 vaccine. (Real vaccines would probably have a whole lot more on the label.) Photo illustration by Igor Golovniov / SOPA Images / LightRocket via Getty Images Vaccine trials have had a weird week. First, there was the exhilarating kickoff of two massive clinical trials for vaccines created by Moderna and Pfizer. Each company is hoping to recruit 30,000 volunteers to test whether its vaccine is effective and safe. This is normal. What’s not normal is a bunch of researchers in Boston who have decided to test a DIY coronavirus vaccine on themselves. At least 20 people have mixed together the vaccine and sprayed it up their noses as part of what they’re calling the Rapid Deployment Vaccine Collaborative (Radvac), according to a truly wild MIT Technology Review story from editor Antonio Regalado. Among the people testing the vaccine is Harvard University geneticist George Church. You may know him from other efforts, including recoding the human genome, Woolly Mammoth Revival, and Genetic Matchmaking. Church was a mentor to Preston Estep, a geneticist who started Radvac in March. As Regalado notes, this is all happening completely outside of any sort of regulation or oversight. Predictably, many bioethicists find this approach to vaccine development... problematic, as Regalado reports: Arthur Caplan, a bioethicist at New York University Langone Medical Center, who saw the white paper, pans Radvac as “off-the-charts looney.” In an email, Caplan says he sees “no leeway” for self-experimentation given the importance of quality control with vaccines. Instead, he thinks there is a high “potential for harm” and “ill-founded enthusiasm.” Church disagrees, saying the vaccine’s simple formulation means it’s probably safe. “I think the bigger risk is that it is ineffective,” he says. But there are also other risks that aren’t directly related to the safety or efficacy of the DIY vaccine on the lab rats self-declared research subjects. There’s been a worrying rise in vaccine mistrust over the past few years, both in the US and around the world. Now, in the middle of a global pandemic, people are still distrustful of vaccines, and it’s getting worse, thanks to rampant misinformation. “Since the outset of the pandemic, vaccine-related falsehoods have ballooned on [Facebook],” reporter Erin Brodwin wrote in a recent article on STAT, “and recent research suggests some of those inaccurate posts are gaining traction among people who weren’t previously opposed to vaccinations.” Radvac isn’t responsible for the current dire state of vaccine attitudes in the US and around the world. But if you’re going to experiment with high-profile drugs in the hopes of changing the world, you should be acutely aware of the world you’re experimenting in. One of the reasons these falsehoods are able to take hold? People who are already scared of the pandemic are also pretty freaked out by the speed at which these vaccines — whether from big firms or small experiments — are being produced. “I just feel like there’s a rush to get a vaccine out, so I’m very hesitant,” Joanne Barnes, a retired fourth grade teacher from Fairbanks, Alaska, told The New York Times earlier this month. Barnes, the Times reported, is someone who is “otherwise always scrupulously up-to-date on getting her shots, including those for shingles, flu and pneumonia.” The trepidation felt by people like Barnes is why vaccine experts and virologists have repeatedly warned against cutting scientific corners in the pursuit of a vaccine. There’s a worry that if those experiments go badly, it could damage people’s willingness to get even a safe, approved vaccine in the future. “A rush into potentially risky vaccines and therapies will betray that trust and discourage work to develop better assessments. Despite the genuine need for urgency, the old saying holds: measure twice, cut once,” Shibo Jiang, a professor of virology at Fudan University in Shanghai, wrote in Nature back in March. As it is, Radvac is measuring and cutting with their own lives, gambling that they can make progress and stay small enough to pass unnoticed by regulatory groups. “What the FDA really wants to crack down on is anything big, which makes claims, or makes money. And this is none of those,” Church told Tech Review. “As soon as we do any of those things, they would justifiably crack down. Also, things that get attention. But we haven’t had any so far.” That’s sure changed. What happens next? It’s all an experiment. Here’s what else was going on this week. Research Children May Carry Coronavirus at High Levels, Study Finds Kids younger than five who had confirmed cases of COVID-19 had nearly 100 times the amount of virus in their noses and throats compared to adults with COVID-19. Older kids had at least as much virus as adults. “One takeaway from this is that we can’t assume that just because kids aren’t getting sick, or very sick, that they don’t have the virus,” Taylor Heald-Sargent, lead author of the study, told The New York Times. (Apoorva Mandavilli / The New York Times) Coronavirus infected scores of children and staff at Georgia sleep-away camp On Friday, the CDC released a report of an outbreak at a sleep-away camp in June. Nearly 600 people (staff and campers) were at the camp, and researchers had test results for 344 of the people there. 260 of the tests came back positive, many of them from children. “This investigation adds to the body of evidence demonstrating that children of all ages are susceptible to SARS-CoV-2 infection and, contrary to early reports, might play an important role in transmission” the CDC report says. (Chelsea Janes/The Washington Post) Covid-19 infections leave an impact on the heart, raising concerns about lasting damage Two studies from Germany found troubling evidence that COVID-19 damages the heart. (Elizabeth Cooney / STAT) The odd, growing list of Covid-19 symptoms, explained This is still a relatively new virus, so researchers are still learning a lot about what kinds of symptoms the disease causes. (Umair Irfan and Brian Resnick / Vox) Development Monkey Business: Experimental vaccines from both Johnson & Johnson and Moderna were able to protect monkeys from catching the coronavirus, according to research published this week. That doesn’t mean that the vaccines will have the same effect in humans, but it is welcome news. “This week has been good — now we have two vaccines that work in monkeys,” virologist Angela Rasmussen told The New York Times. “It’s nice to be upbeat for a change.” (Carl Zimmer, Denise Grady / The New York Times) Perspectives I like to compare this with the difficult task of letting milk simmer on the stove. Most of the time it goes wrong, because the milk can boil over at any time and cause a huge mess. It is just as dangerous to let the virus infections simmer at a low level. — Devi Sridhar, professor of global public health at the University of Edinburgh. Sridhar explains Scotland’s ambitious “zero COVID” policy in a fascinating interview conducted by Veronika Hackenbroch at Der Spiegel. More than numbers “Despite having less than 5% of the global population, nearly a quarter of the 662,000 deaths reported during the pandemic worldwide have occurred in the United States,” NPR reported on Wednesday, when coronavirus deaths in the US topped 150,000. The numbers are still rising. To the more than 17,613,859 people worldwide who have tested positive, may your road to recovery be smooth. To the families and friends of the 679,986 people who have died worldwide — 153,320 of those in the US — your loved ones are not forgotten. Stay safe, everyone. Researchers become their own lab rats with DIY coronavirus vaccine
  5. Anthony Fauci said Thursday the global coronavirus outbreak will not be a pandemic for "a lot longer" because of the development of vaccines, striking a hopeful note even as the situation worsens in the short term. "Certainly it's not going to be pandemic for a lot longer because I believe the vaccines are going to turn that around," Fauci said at an event hosted by the think tank Chatham House. Fauci, the nation's top infectious disease expert, said that while the virus will likely cease raging across the globe as it is now, it could circulate quietly below the surface, at least in certain areas. "Putting it to rest doesn't mean eradicating it," he said. "I doubt we're going to eradicate this, I think we need to plan that this is something we may need to maintain control over chronically, it may be something that becomes endemic that we have to just be careful about." Still, Fauci clearly thinks that vaccines will be a major boost in the fight against the virus. Pfizer reported this week that an interim analysis shows its vaccine was more than 90 percent effective, higher than expectations. Moderna said trial results for its own vaccine candidate may be available by the end of the month. In the meantime, though, coronavirus infections in the U.S. and around the globe are surging. Case numbers are rising in every single state, the U.S. this week set a single-day high for new infections and a record number of people are hospitalized with the disease. Still, Fauci said knowing an end is in sight is all the more reason to keep up precautions like mask-wearing, distancing, and washing hands in the short term. The general public in the U.S. could start getting a vaccine sometime in the spring, officials have said, and high priority groups like health care workers and the elderly, as soon as December. "Ever since it became clear a few days ago that we have a really quite effective vaccine getting ready to deploy, [the message] is rather than 'Hey don't worry you're OK,' it's 'Don't stop shooting, the cavalry is coming but don't put your weapons down, you better keep fighting because they're not here yet,' " Fauci said. Source
  6. We can’t skip steps on the road to a COVID-19 vaccine There’s only so much researchers can do to accelerate the process Photo by Blake Nissen for The Boston Globe via Getty Images The pharmaceutical company Moderna started the last, longest step in the process of testing its COVID-19 vaccine candidate at the end of July — a Phase 3 clinical trial. It’s an enormous undertaking: their goal is to recruit 30,000 people, inject some of them with an experimental vaccine and then follow each and every one of them to see how many contract the coronavirus and how many do not. This will take months, even with the federal government’s Operation Warp Speed compressing the timeline whenever possible. Those months may seem endless when over a thousand people are dying from COVID-19 each day in the United States. The process is long and intensive for a reason, though. Just because a vaccine exists doesn’t mean it’s reasonable or ethical to just give it to people before there’s proof it works, and sticking to the process is why the vaccines on the market today are so safe. “It’s just fundamentally wrong to think that because there’s an emergency, that we should somehow throw out aspects of scientific research,” says Alex John London, director of the Center for Ethics and Policy at Carnegie Mellon University. Researchers already know a lot about a few of the vaccine candidates. Moderna’s vaccine, for example, has gone through both Phase 1 and Phase 2 clinical trials, and it has been tested in monkeys. The trials didn’t raise any major red flags, and they showed that people injected with the vaccine produced antibodies against the coronavirus. But none of them were trying to answer the question people want to know the answer to: can this vaccine stop people from getting COVID-19 in the real world? To answer that question, researchers turn to a Phase 3 trial. They’ll dose thousands of people with the vaccine candidate, and thousands more with a placebo vaccine. Then, they’ll see if fewer people in the vaccine group get COVID-19 than in the placebo group. They’re also watching for any side effects. The amount of data we have on COVID-19 vaccines right now is only a fraction of what scientists need before they’d recommend something get widely distributed. “The evidence that would convince me to get a COVID-19 vaccine, or to recommend that my loved ones get vaccinated, does not yet exist,” Natalie Dean, an assistant professor of biostatistics at the University of Florida, wrote in a New York Times op-ed. If a vaccine is a car, the Phase 1 and Phase 2 trials happen while it’s still in the factory. In those trials, scientists are still trying to assemble a vaccine that might work — they’re figuring out the pieces that they might need and how they should be used. If that assembly process goes well, the vaccine candidate can move into Phase 3, where it’s taken for a heavily monitored ride in test tracks and the real world. “Phase 1 and 2 lets you say, ‘we have a lot of things we need to clarify and decide on,’” London says. “Phase 3 says, ‘great, now let’s test that.’” Those real-world tests are often unsuccessful. Only a small percentage of pharmaceutical products — even those that look promising in early-stage trials — make it through Phase 3 and end up getting approved for use. The success rate is higher in vaccines than treatments, but many of the vaccine successes are for viruses that scientists already know a lot about. New viruses, like the new coronavirus, are much harder to develop vaccines for and have a lower likelihood of success. Sticking with the car metaphor, once a vaccine hits the test track, there’s a chance it’ll stop running (not actually protect people from COVID-19) or, in the worst-case scenario, crash (have some serious side effects). Its first test drives have to be carefully watched, so that the people designing it can monitor exactly what’s happening. If, as the Phase 3 trials roll on, scientists start to see clear signs that it is working, they’d stop the trial early and start working to get it approved by the Food and Drug Administration. “If whatever it is we’re testing is really showing that it’s working, scientists would be remiss to continue to test it in people,” says Karen Maschke, who studies human research ethics at the Hastings Center in New York. But that’s a rare exception to the rule. In almost all cases, you should carry a trial through to the end, she says. It’s particularly important to take vaccines all the way through the process because they’re intended for people who are already healthy. If someone is already sick, the benefits of trying a treatment out (even if it’s unclear how well it actually works) might be worth the potential risks. It’s much harder ethically to justify something that’s still experimental for a healthy person. “A vaccine is the sort of thing that we’re going to administer to hundreds of millions of healthy people, or perhaps even this vaccine could even be given to a billion people,” London says. “We need to know that it’s safe.” Even if it doesn’t come with side effects, giving people an experimental vaccine outside of a clinical trial and before researchers know if it actually works is risky. People who get an unproven vaccine may feel safer and stop taking as many precautions (like wearing masks or avoiding indoor gatherings) against COVID-19, London says. That could increase the spread of the disease if the vaccine doesn’t work. “We need to know if it works because people are going to change their behavior after they get it,” London says. Releasing a vaccine to the public before it’s proven to be safe and effective could also erode public trust in vaccines. “With concerns about science, and anti-science sentiment, you have to be really, really careful that you get enough data,” Maschke says. Researchers need to be able to point to the number of people they tested the vaccine in and their statistical analysis as justification for a recommendation. “Trust in the process of developing new drugs and new medicines is fragile,” London says. “We can’t put it in jeopardy.” There isn’t usually such focused attention on the clinical trial process, London says. “The public has a window into a discussion that they’re not usually a part of,” he says. That process can be confusing, even at the best of times. Press releases, sound bites, and jargon can create the illusion that scientists know more about vaccine candidates than they do, or that they look more promising than they actually are. For example, when experts say that a vaccine performed well in a Phase 1 trial, they mean that they didn’t see anything that would keep it from moving on to the next stage of the process. “It doesn’t mean the things the public is interested in — is it safe; if I take this, does it mean I won’t have any adverse events a year later; and is it going to protect me if I’m exposed to the coronavirus,” he says. Answering those questions is possible, but it will take time. Going at warp speed can save some time, but solid, conclusive answers are worth the wait. We can’t skip steps on the road to a COVID-19 vaccine
  7. The Ars COVID-19 vaccine primer: 100-plus in the works, 8 in clinical trials Here's where we are and what may lie ahead for a vaccine against COVID-19. Enlarge / HUBEI, CHINA - APRIL 15: (CHINA MAINLAND OUT)220 volunteers from Wuhan are vaccinated with the novel coronavirus vaccine, which is in a human clinical trial. Getty | TPG 99 with 61 posters participating The clearest way out of the COVID-19 crisis is to develop a safe, effective vaccine—and scientists have wasted no time in getting started. They have at least 102 vaccine candidates in development worldwide. Eight of those have already entered early clinical trials in people. At least two have protected a small number of monkeys from infection with the novel coronavirus, SARS-CoV-2, that causes COVID-19. Some optimistic vaccine developers say that, if all goes perfectly, we could see large-scale production and limited deployment of vaccines as early as this fall. If true, it would be an extraordinary achievement. Less than four months ago, SARS-CoV-2 was an unnamed, never-before-seen virus that abruptly emerged in the central Chinese city of Wuhan. Researchers there quickly identified it and, by late January, had deciphered and shared its genetic code, allowing researchers around the world to get to work on defeating it. By late February, researchers on multiple continents were working up clinical trials for vaccine candidates. By mid-March, two of them began, and volunteers began receiving the first jabs of candidate vaccines against COVID-19. It’s a record-setting feat. But, it’s unclear if researchers will be able to maintain this break-neck pace. Generally, vaccines must go through three progressively more stringent human trial phases before they are considered safe and effective. The phases assess the candidates’ safety profile, the strength of the immune responses they trigger, and how good they are at actually protecting people from infection and disease. Most vaccine candidates don’t make it. By some estimates, more than 90 percent fail. And, though a pandemic-propelled timeline could conceivably deliver a vaccine in as little as 18 months, most vaccines take years—often more than 10 years, in fact—to go from preclinical vetting to a syringe in a doctor’s office. Abridging that timeline can up the risk of failure. For instance, vaccine candidates usually enter the three phases of clinical trials only after being well tested in lab animals that can model the human disease. But, with such a new virus, there is no established animal model for COVID-19. And amid a devastating pandemic, there’s not enough time to thoroughly develop one. Some researchers are now doing that ground-level animal work in parallel with human trials—such as the small monkey trials mentioned above. Researchers already have reason to be a little anxious about the safety of any COVID-19 vaccine. When they tried in the past to make vaccines against some of SARS-CoV-2’s coronavirus relatives, they found a small number of instances when candidate vaccines seemed to make infections worse. That is, these candidate vaccines seemed to prompt berserk immune responses that caused lung damage in monkeys and liver damage in ferrets. Researchers still don’t fully understand the problem and don’t know if it could happen in humans, let alone if it will show up with the new candidate vaccines against SARS-CoV-2. But we may soon know the answers. As the pandemic tops the grim milestone of three million cases worldwide and well over 200,000 deaths, researchers are relentlessly moving forward with vaccine development. Here's where the scientific community currently stands in its frenetic effort. First, the basics Researchers are using a wide variety of tools and techniques to develop a vaccine—some are tried and tested, others are fresh and unproven. Regardless of the strategy, they all aim to do the same thing: train the immune system to identify SARS-CoV-2 (or some element of it) and destroy it before it establishes an infection and causes COVID-19. The way a vaccine can pull this off, typically, is by feeding immune cells a signature element of a disease-causing germ, such as a unique protein that coats the outside of a dangerous virus. From there, a type of white blood cell called B cells can generate antibodies that specifically recognize and glom onto those signature germ elements. Antibodies are Y-shaped proteins, which have their germ-specific detecting regions on their outstretched arms. The base of their “Y” shape is a generic region that can signal certain immune responses if they detect an invading germ. A strong, effective vaccine can generate so-called neutralizing antibodies. These antibodies circulate in the blood, surveilling the whole body after a vaccine is given. If the germ they’re trained to detect actually shows up, the antibodies can swarm and paralyze it. The base of the antibodies—now dangling off their smothered target germ—can then signal immune cells to help finish the job. In the case of COVID-19, the goal of candidate vaccines is to train our immune systems to make antibodies that specifically detect and destroy SARS-CoV-2 (which is, again, the novel coronavirus that causes COVID-19). Though there’s a lot we don’t know about SARS-CoV-2, we know enough of the basics to direct early vaccine development. We know that SARS-CoV-2 is a betacoronavirus related to two other notorious betacoronaviruses: SARS-CoV-1, which causes SARS (severe acute respiratory syndrome), and the Middle Eastern respiratory syndrome coronavirus (MERS-CoV), which causes MERS. Coronaviruses, generally, keep their genetic blueprints in the form of a large, single-stranded, positive-sense RNA genome, which is bundled into a round viral particle. That genetic code provides the molecular instructions to make all of the components of the virus, including enzymes required to make copies of the virus’s genome, and the virus’s famous spike protein. The spike protein is what the coronaviruses use to grab ahold of host cells—that is, human cells they infect or the cells of any other animal victim. Once the virus latches on with its spike protein, it gets into the cell and hijacks the cell's activities, forcing it to help manufacture viral clones, which then burst forth to infect more cells. There are many copies of the spike protein on the outer surface of coronaviruses, creating a spikey exterior—think a cartoon sea mine. The pointy adornments are actually what give coronaviruses their name. Under an electron microscope, the spikes give the viral particle a crown-like appearance, hence corona viruses. But more importantly, the spike proteins are a prime target for antibodies. And, because we have the whole genome sequence for SARS-CoV-2, researchers have a good start at figuring out effective ways to engineer vaccines to attack the spike proteins and other critical components of the virus. Vaccine platforms There are many ways to try to train the immune system to fight off a specific germ or specific elements of germs, such as SARS-CoV-2 or the SARS-CoV-2 spike proteins. Here are the general categories currently in play: Live-attenuated vaccine: These vaccines use whole viruses that are weakened so they can no longer cause disease. This is a well-established method for creating vaccines. In the past, researchers weakened viruses by growing them in lab conditions for long periods of time—which is a bit like domesticating germs. The cushy, all-inclusive petri-dish lifestyle can essentially allow viruses and bacteria to adapt to their tranquil surroundings and lose virulence over time. But, it can take a while. Scientists grew the measles virus in lab conditions for nearly 10 years before using it for a live-attenuated vaccine in the early 1960s. Nowadays, there are faster, more controlled approaches to engineer weakened viruses, such as targeted mutations and other manipulations of a virus’s genetic code. Live-attenuated virus vaccines have the advantage of generating the same variety of protective antibodies as a real infection—without causing a pesky, life-threatening disease, for the most part. But there are risks. Because the virus can still replicate, certain people (particularly those with immunodeficiencies) may have severe reactions. Though the newer strategies for weakening viruses may reduce these risks, they still require extensive safety testing before reaching the market. That said, this is a vaccine platform that has already proven successful. Several vaccines in use are live-attenuated vaccines, including vaccines for chickenpox and typhoid. If such a vaccine proved effective at preventing COVID-19, we already have the know-how and infrastructure to quickly scale up production to make these vaccines. Inactivated vaccine: This is another straightforward, old-school method that uses whole viruses. In this case, the viruses are effectively dead, though, usually inactivated by heat or chemicals. These corpse viruses can still prime the immune system to make neutralizing antibodies; they just do it less efficiently. The advantage of this strategy is that it is relatively simple to make these types of vaccines and, because the viruses don’t replicate, there is no risk of infection and less risk of severe reactions. Disadvantages include that inactivated, non-replicating viruses don’t elicit as strong of an immune response as a disease-causing or weakened virus. Inactivated vaccines always require multiple doses and may need periodic booster shots as well. Like weakened virus vaccines, using a whole viral particle gives the immune system many potential viral targets for antibodies. Some may be good targets to neutralize a real infection, and some may not. But, using an inactivated virus is a proven method. For instance, some existing vaccines against polio, hepatitis A, and rabies use this method. Viral vector-based vaccine: For these vaccines, researchers take a weakened or harmless virus and engineer it to contain an element of a dangerous virus they want to protect against. In the context of COVID-19, this might mean engineering a harmless virus to produce, say, the spike protein from SARS-CoV-2. This way you get the immune response to a live but benign virus, coupled with the likelihood of having antibodies that target a specific critical protein from the dangerous SARS-CoV-2. This, too, is a proven strategy for effective vaccines. The newly approved Ebola vaccine, for instance, uses this method. Subunit vaccines: These are bare-bones vaccines that include only a component of a dangerous virus to elicit immune responses. For COVID-19 vaccines, the spike protein is—no surprise—a popular candidate. Subunits can be delivered in formulations with adjuvants—accessory ingredients that can enhance immune responses. One common adjuvant is alum, an aluminum salt, long known to be useful for vaccines. Some newer subunit vaccines come in snappier packages, however. These include artificial “virus-like particles” (VLPs) and nanoparticles. Subunit vaccines are already an established vaccine platform. The HPV vaccine in use involves a VLP that feeds the immune system proteins from the HPV’s outer shell—which can then be targeted by antibodies. RNA and DNA vaccines: These are among the newest types of vaccines—and among the shakiest. There are currently no licensed vaccines that use this method. But researchers are optimistic about their potential. The basic idea is to deliver genetic material of a virus—either in the form of DNA or RNA—directly to human cells, which are then somehow compelled to translate that genetic code into viral proteins and then able to make antibodies against those. Some of the details of how these candidate vaccines work are proprietary and unproven, so it’s difficult to assess how likely they are to succeed or how easy it will be to scale up vaccine production if they are successful. Enlarge / Adapted from a review of candidate vaccines. This includes information about vaccine development that is not publicly available. It is a larger list of candidates than what is reported by the WHO. Ars Technica Potential pitfalls As mentioned earlier, in some previous work on developing a vaccine against SARS-CoV-1—the virus behind SARS—researchers came across a few instances where candidate vaccines seemed to make disease worse in animal models. This led to some instances of organ damage in a few animal models, namely monkeys, ferrets, and also mice. So far, it’s unclear what was going on there. Some researchers have speculated that it may be a form of Antibody-Dependent Enhancement (ADE). Very generally, this is a scenario in which the immune system makes antibodies against an invading germ, but those antibodies are not able to neutralize the germ completely. This can make the situation worse if the shoddy antibodies signal for immune cells to respond while the germ is still infectious. Basically, the antibodies are just recruiting immune cells to be the germ’s next victims. And this, in turn, can lead to additional—excessive—immune responses that end up damaging the body. One of the best understood examples of this occurs with dengue viruses. There are four types of dengue viruses that circulate (in people and mosquitoes), and research suggests that some antibodies to one type of dengue may sometimes generate ADE in subsequent infections or exposures with other types of dengue. This is why researchers think that some patients with dengue fever, which can be a mild disease, go on to develop dengue hemorrhagic fever. This is a rare but severe form of the disease in which immune cells release chemicals called inflammatory cytokines that end up damaging the circulatory system, leading to blood plasma leaking out of capillaries. From there, the patient can go into shock and die. But, many researchers are not convinced that ADE is behind some of the problems seen with early SARS vaccines—nor that ADE will necessarily be an issue with a COVID-19 vaccine. For one thing, the berserk immune responses seen in the animal models don’t seem to involve some of the same immune system components seen in well-understood cases of ADE, like dengue. “There’s no clear evidence that ADE is an issue,” microbiologist Maria Elena Bottazzi tells Ars. Bottazzi is the associate dean of the National School of Tropical Medicine at Baylor College of Medicine. Instead, Bottazzi and colleagues hypothesize that something about the coronaviruses and whole-virus vaccine candidates may induce an excessive, aberrant inflammatory response, potentially through the activity of specialized, pro-inflammatory immune cells called T helper 17 cells, which are linked to inflammatory autoimmune diseases. This may help explain why some patients with the most severe forms of COVID-19 seem to experience so-called “cytokine storms,” which are like a disastrous deluge of pro-inflammatory signals unleashed by the immune system that end up causing damage to the body—just like in the animal models. Much of this is still speculative, but Bottazzi says what we know so far may be helpful for directing vaccine development strategies. She notes that the excessive immune responses may mainly occur when the immune system is presented with a whole, intact coronavirus particle. Something about interacting with that whole particle may send our immune systems into a tailspin, the thinking goes. A safer strategy may be to use a subunit vaccine or another more targeted approach to train our immune systems—an approach that only shows the immune system what it needs to see to defeat the virus. Many vaccine developers are already on board with this thinking, it seems. Bottazzi notes that most of the candidates in development now do not involve the whole virus, but subunits, genetic material, or other targeted strategies. “Having the whole virus, of course it has higher risks, so the new platforms are actually selecting for better candidates,” she says. Bottazzi and her colleagues are themselves now working up such a subunit vaccine candidate for SARS-CoV-2, which follows up on their vaccine work for SARS-CoV-1. The vaccine includes just a portion of the SARS-CoV-2 spike protein—the precise segment that actually binds to human cells. She notes that further questions about potential ADE or excessive immune responses to any candidate vaccine might be more closely looked at further along in vaccine development, perhaps in phase II trials. But, right now, “it’s not a high-ranking concern,” she says. Timing Another potential problem vaccine developers should keep in mind is how long the antibody responses may last in the body. Past research has suggested that coronaviruses that cause just common colds—there are four strains of these that circulate in humans—don’t prompt long-lasting antibodies. A person may only be protected for a few years. Ideally, vaccines should be optimized to generate the strongest immune response possible that will, hopefully, offer long-lasting if not life-long protection. But, if immune responses to an otherwise effective vaccine wane over time, and SARS-CoV-2 becomes an endemic disease or comes in seasonal waves, we may have to look at periodic boosters until a more effective vaccine is developed. We already have annual vaccines for influenza, but this is because the influenza virus mutates so quickly that our immune system may not recognize strains from one year to the next. Also, there are different mixes of strains circulating from season to season. Both of these issues lead to the need for season-specific vaccine formulations. So far, SARS-CoV-2 does not seem to be mutating in a particularly fast or problematic fashion, suggesting that we may not need seasonal shots—at least not for these reasons. Early front-runners With all of this in mind, vaccine developers have charged ahead. There are currently at least 102 candidates, and eight of them are in clinical trials. One of the earliest was an RNA vaccine, called mRNA-1273, from biotechnology company Moderna. As we mentioned earlier, vaccines based on genetic material are unproven so far. Moreover, because the technology is so new, much of it is still proprietary, so outside researchers don’t know a lot about how these vaccines work. As such, they’re difficult to assess from the outside—and it’s difficult to know how easy it will be to scale up production for worldwide vaccination campaigns (if they work), Bottazzi says. Based on what we know about Moderna’s work, their vaccine contains the genetic blueprints for the SARS-CoV-2 spike proteins. The genetic code is modified to have artificial components—such as pseudouridine instead of RNA’s usual uridine—so that the immune system doesn’t automatically recognize the vaccine as foreign genetic material and try to destroy it. The genetic material is also packaged for cell delivery in a lipid nanoparticle. Moderna, working with the National Institutes of Health, got a clinical trial set up in February and gave its first doses to humans on March 16. If all goes to plan, the company has suggested that it could have a vaccine ready for frontline healthcare workers by this fall. Eight candidate vaccines in clinical evaluation Platform Type of candidate vaccine Developer Current stage of clinical evaluation/regulatory status—coronavirus candidate Same platform for non-coronavirus candidates Non-replicating viral vector Adenovirus Type 5 Vector CanSino Biological Inc./Beijing Institute of Biotechnology Phase 2: ChiCTR2000031781 Phase 1: ChiCTR2000030906 Ebola Non-replicating viral vector ChAdOx1 University of Oxford Phase 1/2: NCT04324606 MERS, Influenza, TB, Chikungunya, Zika, MenB, plague DNA DNA plasmid vaccine with electropolation Inovio Pharmaceuticals Phase 1: NCT04336410 Multiple candidates Inactivated Inactivated Wuhan Institute of Biological Products/Sinopharm Phase 1: ChiCTR2000031809 Inactivated Inactivated Beijing Institute of Biological Products/Sinopharm Phase 1 (regulatory approval) Inactivated Inactivated + alum Sinovac Phase 1: NCT04352608 SARS RNA mRNA BioNTech/Fosun Pharma/Pfizer Phase 1/2: 2020-001038-36 RNA LNP-encapsulated mRNA Moderna/NIAID Phase 1: NCT04283461 Multiple candidates Source: WHO Meanwhile, in China, biotechnology company CanSino Biologics began a trial March 17 for its viral vector-based vaccine candidate. The strategy packages genetic material from SARS-CoV-2 into a weakened adenovirus strain. The company has already gotten to work on a Phase II trial. Beijing-based Sinovac Biotech made headlines this month after its whole-virus inactivated SARS-CoV-2 vaccine candidate was shown to protect a small number of monkeys from COVID-19 in early lab tests. Its Phase I clinical trials in humans began on April 16. The results are positive, but some researchers are anxious to see more testing and safety data. Researchers at Oxford University are also off to a good start with their viral vector-based vaccine candidate. They have packaged the SARS-CoV-2 spike protein in a weakened adenovirus, similar to CanSino’s approach. And like Sinovac, their vaccine has protected a small number of monkeys in early lab experiments. Oxford researchers began dosing trial participants last week. The researchers told The New York Times that if the trials go to plan, they could produce millions of doses by September. The latest, ever-expanding and updating list of candidate vaccines assembled by the World Health Organization can be found here. Source: The Ars COVID-19 vaccine primer: 100-plus in the works, 8 in clinical trials (Ars Technica)
  8. AI-Powered Biotech Can Help Deploy a Vaccine In Record Time Simulators that can rapidly test trillions of options would accelerate the slow and costly process of human clinical trials. A human doctor may come up with a few dozen drugs that may treat a disease. The actual number of theoretical drug possibilities is in the trillions.Photograph: Justin Sullivan/Getty Images The magnitude of the Covid-19 pandemic will largely depend on how quickly safe and effective vaccines and treatments can be developed and tested. Many assume a widely available vaccine is years away, if ever. Others believe that a 12- to 18-month development cycle is a given. Our best bet to reduce even that record-breaking timeline is by using artificial intelligence. The problem is twofold: discovering the right set of molecules among billions of possibilities, and then waiting for clinical trials. These processes ordinarily take several years, but AI holds the key to radically shortening both. This is where combining AI with biotechnology is headed, and within several years all vaccine and medication development could be done this way. We can already shorten the development time of a Covid-19 vaccine using this method. Although a human trial of a vaccine or other treatment is regarded as necessary today before widespread use is approved, even large-scale trials are very imperfect, time-consuming, and expensive. A human doctor may come up with a few dozen drugs that may treat a disease. The actual number of theoretical drug possibilities is in the trillions. The current method for testing these few treatments is to organize a few hundred human subjects and then test them over about a year and a half, at a cost of hundreds of millions of dollars. Very often, the first several solutions tested on humans are not ideal and lead to other solutions that also take a few years to develop and test. We are literally stuck, watching people succumb to a disease for years while only a few possible solutions are tested. Not much can be advanced until those results are available. We are seeing the beginnings of a profound paradigm shift in health technology. AI simulations have the potential to test all of the trillions of possibilities with tens of thousands of (simulated) patients for a (simulated) period of years, and do all of this in a matter of hours or days. In 2019, for example, researchers at Flinders University in Adelaide, Australia, created a “turbocharged” flu vaccine in part by using a biology simulator that used AI to find drugs that activate the human immune system. In a matter of weeks it created trillions of chemical compounds, and the researchers used another simulator to see if each compound would be useful as an immune-boosting drug against the disease agent, selecting the ideal formulation. US researchers are now testing this optimized flu vaccine on human subjects. Moreover, in the search for antiviral drugs for Covid-19, Argonne National Laboratory has used five of the world’s most powerful supercomputers to narrow a billion molecules down to a few thousand. Then, with a combination of physics simulations to model the microscopic chemistry and deep learning for pattern recognition, they identified about 30 of the most promising candidates for laboratory study. To fight the coronavirus much more rapidly and effectively, more labs need to use AI to simulate trillions of possibilities, and then use human trials for the most promising ones. These examples mark only the beginning of AI’s contribution to overcoming health problems. Today we can simulate how small molecules interact with certain virtual or human proteins. As these methods take off in the coming years, we will be able to test all trillions of possible solutions to each health problem very quickly. Using neural nets with sufficient computational power will go way beyond what humans can possibly do on their own. Given the exponential nature of progress in this field, I believe that by the end of the decade we will be able realistically model all biology and simulate interventions for diseases without the need for human trials. Amplifying progress in creating new medications for diseases is among the most profound near-term objectives of AI. Such technology will improve medicine for a vast array of diseases, but it will also be enormously valuable when the next pandemic strikes—whenever that happens. It might have a natural origin. It might be a terrorist bioweapon. It might spread faster than Covid-19, and be 10 or 20 times as lethal. Deploying an effective cure in weeks instead of a year could save tens of millions of lives. Source: AI-Powered Biotech Can Help Deploy a Vaccine In Record Time (Wired)
  9. Printing vaccines at the pharmacy or at home will be the way of the future Op-ed: Our current model of manufacturing stockpiles won't work against bioterror or superbugs. Enlarge / Artist's impression of a vaccine printer. Getty / Aurich Lawson We're running a series of companion posts this week to accompany our special edition Ars Lunch Break podcast. This is the third of three guest posts centered around Rob Reid's TED talk from Tuesday. Today, microbiologist Andrew Hessel weighs in with his opinions and recommendations about the future of biomanufacturing. The US government doesn’t skimp on bio-preparedness. Vaccines and other countermeasures are carefully developed in anticipation of disease outbreaks or bioterrorist attacks. The Strategic National Stockpile maintains a hefty inventory of medicines, supplies, and equipment, which can be shipped almost anywhere within 12 hours. In situations ranging from the 2001 anthrax attacks to 2016’s Zika scare, Americans have been lucky to have strong biodefenses. But as anti-vaccine hysteria allows measles to regain long-lost beachheads, we’re reminded that human folly is a dynamic element of the disease landscape. Meanwhile, the number of human actors and actions in a position to stir the pot is set to explode. Tremendous improvements in core bioengineering technologies are tearing down the technical and economic barriers that once prevented the development of "designer" viruses and bacteria. Those entrusted with our defense will inevitably face an even more chaotic battlefield than exists today. Currently, our vaccine inventory is designed to defend against a very short list of well-known diseases. Vaccine fragility calls for refrigeration and expiration dates, as well as regular testing and replenishment. Deployment requires transportation, communication, and person-to-person networks to be functioning. If infections can arise from engineered organisms with no natural precedents, agility in response is paramount. If we develop an agile threat response system, it can handle engineered and emerging diseases, as well as the old threats from familiar pathogens, which would make our existing National Stockpile obsolete. Be flexible A model for truly effective biosecurity lies in the dynamism of our own immune systems. Human immunity is astoundingly sensitive and nimble, capable of sensing and responding to almost any invader. The technology to build a global pathogen detection network that sniffs out threats in a way similar to our bodies' immune systems is within reach. Technology drove exponential curves that cut the cost of genomic sequencing by a factor of three million. As similar approaches expand to other areas of biotechnology, highly acute sensors could become inexpensive enough to follow the path that smoke detectors took to the ceilings of every home and business within a decade or two. Instead of changing batteries once a year, you might change a pack of solutions every few months. But detection has limited value if the system can’t respond to carefully identified threats. And key elements of our responsiveness are atrophying. Fewer vaccines and antibiotics are being made as companies focus on higher-margin medicines. Pharmaceutical manufacturing requires specialized facilities that are not widely distributed. Drug development invariably takes years. Should a truly novel pathogen appear—due to bioterror, bio error, or a natural run of bad luck in a world that can produce things like Ebola by chance—a defense centered on stockpiles could be swiftly outmaneuvered. It’s time to rearchitect our defenses by leveraging the very force of proliferation that threatens to destabilize the system. Rather than warehouses of refrigerated cures for static diseases, we need a highly distributed agile system for producing vaccines and medicines. We need biomanufacturing at the edge—not just the hub. But don’t envision edge biomanufacturing as giant factories and smokestacks. Instead, think of bio-printers that resemble inkjets, flexible enough to print a wide array of medicines. Print on demand This isn’t as far-fetched or as far-off as some might imagine. Medical printer prototypes are already out there. For instance, biotechnologist Craig Venter’s team unveiled its “digital-to-biological converter” in 2017. About the size of a chest freezer, the "converter" is a DNA printer mated to a liquid handling robot. It produces genetic “programs” for the downstream production of biologics, including proteins, vaccines, and viruses. These capabilities are now being miniaturized for the desktop. While traditional vaccines involve producing proteins or even entire organisms on a massive scale, tests have shown that it’s possible to vaccinate an animal by injecting some of its cells with DNA that encodes one of a pathogen’s proteins. So a miniaturized DNA printer may be all we need to protect ourselves from many diseases. Imagine versatile self-upgrading bioprinters extending into every pharmacy and medical office—each with a vast FDA-sanctioned repertoire of templates. This would be a game changer in public health and emergency response. Prepping the nation for flu season? No need to guess which flu variant will be spreading months in advance and then bet it all on a massive centralized production run. Just print the precise vaccine required at thousands of locations across the country, adjusting the design to account for genetic drift. And in a worst-case bioweapon nightmare, antidotes made in every neighborhood will get to where they’re needed, unlike ones made in a lone urban center with fast-unraveling distribution networks. Low food miles are fashionable. Low vaccine miles could be lifesaving. Biochips and beyond We can and should push our production nodes to be ever smaller, cheaper, and more widespread. This is already happening with key enabling technologies. We've moved beyond microfluidics to nanofluidics and molecular electronics. DNA sequencing is already done with “biochips” that are close kin to electronic chips; DNA and protein synthesizers may soon be chipsets, too. These would control the synthesis of molecules in a way that gets rid of the need for complicated chemical reactions and extensive infrastructure to supply large volumes of the right precursors. Entire biotech and pharmaceutical companies could be reduced to a few square millimeters, ready to be installed in "smart" syringes, inhalers, patches, and implants. “Biomanufacturing at the edge” could start at the pharmacy, then move to our homes, then to our pockets, and finally on or under our skin. This last step is feasible because of something I mentioned above: human cells are tiny manufacturing plants, which continuously make thousands of proteins and other compounds based on blueprints stored in DNA. If we give them the right DNA, they can make vaccines for us. Looking past the near term and into the murky future, our ultimate agile defense layer could be built around tiny biochips, which print nucleic acids and then deliver them into our bodies. Imagine a dermal patch that integrates these chips with nanoneedles, which inject their output into the skin’s epithelial cells. These cells could then churn out protein-based therapeutics targeting the latest biohazard. Some well-targeted R&D muscle could make this sort of system attainable within a decade or two. Paired with a biosensor network of the sort that George Church described on Ars yesterday, it could supercharge global public health efforts, improve national biosecurity, and put the biopharmaceutical industry on a technical foundation better suited to address the demands and threats of the 21st century. Andrew is the CEO of Humane Genomics, a seed stage company developing synthetic viruses targeting cancer. He is also a co-founder of the Genome Project-write, an international scientist-led effort to advance whole genome engineering. Source: Printing vaccines at the pharmacy or at home will be the way of the future (Ars Technica)
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