Category: Corona Virus Vaccine

A potential vaccine for COVID-19 has been developed and tested successfully in mice, researchers reported Thursday.

"We'd like to get this into patients as soon as possible," said Andrea Gambotto, associate professor of surgery at the University of Pittsburgh School of Medicine and co-author of a paper announcing the vaccine in the journal EBioMedicine.

As far as reaching clinical trials,"we would like to thinka month, give or take. Maybe two months. We just started the process," said co-author Louis Falo, a professor and chairman of the Department of Dermatology at the University of Pittsburgh.

Thursday'sannouncement, more than three months into a pandemic that has killed 50,000 people and sickened almost 1 million worldwide, presents an urgent challenge to government regulators, who must weigh how much to speed up the vaccine approval process.

Plasma: The first US coronavirus patients are being treated with convalescent plasma therapy.

'Its time to save people': Synagogue members who had coronavirus donate blood to help others

Vaccinesoften take years to receive approval from the U.S. Food and Drug Administration. Yet on March 16, the first four healthy volunteersin Seattle received adifferent potential COVID-19 vaccine, made by a company called Moderna and administered in a small clinical trial at Kaiser Permanente Washington Health Research Institute.

Though the vaccine being tested in Seattle uses a new, faster but untested technology,the one developed in Pittsburgh employs the sametechnique used influ shots. The Pittsburgh vaccine uses lab-made viral proteinto builda person's immunity to the virus.

Tests in mice found that the vaccine spurred a wave of virus-fighting antibodies within two weeks.

"There are many, many vaccine candidates in various stages of testing," saidDavid O'Connor, professor at the University of Wisconsin School of Medicine and Public Health, who saw the published paper for the first time Thursday.

O'Connor saidshowing that a vaccine generates an immune response is"an important first step in determining which vaccines should move forward, but is only the first of many steps along the way to a useful vaccine. This paper shows some of this 'first step'data."

The potential COVID-19 vaccinefollows up on researchGambottoand Falo did in December 2003 when they were poisedto proceed to clinical trials with a vaccine for another coronavirus, Severe Acute Respiratory Syndrome. At the time, the journal Nature reported, "SARS vaccines speed toward clinic."

But the outbreak had already waned. The World Health Organization declared SARS contained in July 2003.

Funding for the SARS vaccine vanished.

"SARS CoV-2 is teaching us that it is important to react and (follow) all the way through," Gambottosaid. "Yes, it was a mistake not to test the vaccine back then."

Some scientists suggested that a vaccine for one coronavirus would probably have offered at least some protection from all of them.

The Pittsburghresearchers developed a vaccine to treat Arabian camels for another coronavirus, Middle East Respiratory Syndrome (MERS). Like SARS and COVID-19, MERS jumped from animals to people,infectingalmost 2,500 andkilling almost 860 since its discovery in 2012.

Gambotto saidtheyadapted techniques they had developed for previous coronavirusesto create one specifically designed for the virus that causesCOVID-19; theprocess of translating their work foruse onCOVID-19took the scientists 10 to 12 days. They collaboratedwith11 other scientists, including two from Erasmus Medical Center in Rotterdam, the Netherlands.

Gambotto and Falo said theirvaccine would be delivered to the upper armbut would not requirea shot from a needle asthe flu vaccine does.

The scientists developed a fingertip-sized patch that contains 400tiny needles, each just half a millimeter. The two scientistscompared the patch to a Band-Aid and said it would feel a lot like having Velcro pressed against the skin.

The needles, made from sugar and protein pieces, would penetrate the upper level of skin, absorb moisture from the skin and release molecules. The molecules would prompt the immune system to makeantibodies thatattack the virus.

The Pittsburgh researchers touted two advantages tothevaccine they call PittCoVacc.

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The vaccine does not have to be frozenwhen stored or transported; it can sit atroom temperature. That wouldmake the vaccine much cheaper to deliver to poorer countries.

Though the researchers could not say exactly how much a dose of the vaccine would cost, they estimated that the patchof needles used to deliver the vaccine would probably cost less than $10 apatch.

The technique employing the tiny needlesreleases a highly concentrated, much smaller amount of viral protein. The scientists said a single person would be able to make hundreds of vaccine patches a day.

The vaccine was developed without using the live virus that causes COVID-19. Scientists used DNA molecules made in the lab.

When released from the patch, the vaccineexploits the crucial part of the virus that latches onto human cells, the Spike protein.

The virus' Spike protein usually acts like a key opening up human cells and allowing the virus to invade. The vaccine acts a little like gum in a lock, preventing the key from working and keeping the virus from entering human cells.

Early in the pandemic, health officials took pains to stress that a vaccine would probably take18 months to develop, test and be ready for human use. Whether the first vaccines will take that long to reach people is not known, and many scientists greetnew reports such as the one from Pittsburgh with caution.

O'Connor, from the University of Wisconsin,stressed that vaccine makers have been forced by the urgency of fighting a pandemic to move when "there is much that we don't know about this virus." In particular, it's unknownhow long a person has immunity both natural immunity from having fought the virus and survivedand theimmunity inducedby vaccines.

"Dovaccines last for months? Years? An entire lifetime?" he asked.

Scientists have been working furiously to develop two possible treatment methods: the use of plasma from recovered COVID-19 patientsand drugs that have been found safe for use in people, such as the anti-malarial chloroquine.

Hospitals have begun using survivorplasmaon a compassionate, experimental basis.

Follow Mark Johnson on Twitter:@majohnso

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Tests of potential coronavirus vaccine spur growth of virus-fighting antibodies - USA TODAY

Jacob Heilbrunn: How does the COVID-19 crisis end?

Paul Offit: German chancellor Angela Merkel said it best: We need to get to a doubling time of longer than ten days. The number of hospital admissions and deaths caused by COVID-19, those doubling intervals, is more than ten days. For example, on March 26 we had one thousand deaths; on March 28, two thousand. Thats a doubling time of two days. By April 1 we had four thousand deaths. That means we had a doubling time of four days. If you can get to a ten-day doubling time, it is likely that hospital discharges will exceed admissions and you can say that you accomplished what you wantedno longer overwhelming the healthcare system. Thats what you are worried aboutnot that you cant take care of these patients, but that you cant take care of any patients.

Once you get there, things can loosen up and you can go back to work even though there still may be cases and deaths. But that is not the goal. The goal is to not overwhelm the health system and allow us to go back to work. When do we get there? Im going to predict that by the end of April, things start to look better and we start to see a gradual increase in our doubling times.

Heilbrunn: Do you think we are likely to reach the high end of the predictions of deaths? Or is that just unknowable?

Offit: Its surprising, isnt it? We know that lockdowns, or sheltering in place, works. China, Singapore, Japan, and South Korea were all able to pretty much end the spread of this virus while knowing that therehad to be tens of millions of people in those countries who were still susceptible. Yet still, they were able to end itthats a good sign.

Now Vice President Mike Pence has said that he thinks we are mimicking Italy. Italy has 13,000 deaths right now and they are roughly one-fifth our size. That would come out to 65,000 deaths, but they are predicting as many as 240,000 deaths. Which means that Italy would have to have 50,000 deaths, for us to be Italy. Its just surprising that it could get that bad; even though Italy is still suffering deaths, it looks like their doubling time is about eight days. So it should be coming off this curve and I dont see this 240,000 death estimate. I dont see that. But they are also close to the data, so they could be seeing something Im not.

We did many things wrong. We were slow to ban travel from China. We were very slow to do testingSouth Korea had already done 150,000 tests by the time we had done fewer than 500. We were slow to lockdown. We had a president who, if anything, tried to play this down: We've got it under control, its only a few cases, dont worry about it. And we were very slow to supply protective gear, ventilators, etc. so people were not getting the care they need or being protected in the manner they need to be. So weve done a lot of things wrong. As a consequence, we are doing worse than most countries.

Heilbrunn: So you would have banned travel from China earlier? President Donald Trump keeps bragging that he did it quickly.

Offit: Right, but if you look a little more closely at how that played out, he had to be convinced to do that. He didnt want to offend his friend President Xi [Jinping]. China was not a good actor here. We should not have had to have a whistleblower to tell us that there was a novel virus that was killing people in Wuhan. They should have been quick to tell the world that this was going on so the world could prepare for it. They didnt do that. But the moment it did become clear, Trump was very slow to ban travel. But once the virus was here, once there was community spread, it didnt really matter.

You can make the same case for what is happening in New York. We were pretty slow to ban travel from Europe, when clearly there were problems in Spain, Italy, and France. I suspect that may be the reason that New York suffers so much nowthere was a lot of travel from COVID-heavy territories, regions, or countries, coming into LaGuardia, coming into JFK.

Heilbrunn: You were the co-inventor of the rotavirus vaccine. How critical do you think it is that we develop a vaccine against the coronavirus? Or do you think the virus will largely burn itself out?

Offit: We certainly should not assume that it will burn itself out. We should make a vaccine as quickly, efficiently, and safely as possible. There is some good news about the vaccine. Human trial studies done decades ago show that if you are inoculated with one of the four strains of human coronavirus that circulates in our country every year and are challenged with that virus a year later, you are protected. Good. That means that there is protectionits probably years, not decadesbut thats a good sign. You also know which protein you are interested in. You are interested in that spike proteinthe glycoproteinthats the protein that attaches to cells. If you can prevent the virus from attaching to cells, then you cant get infected. And we live in an age of recombinant DNA technology where we can make that protein itself in a manner similar to the Hepatitis-B or HPV vaccine, or we can use either messenger RNA or DNA vaccines that express that protein.

So the messenger RNA approach is the one being used by Moderna and that is already in the human trials that Dr. Anthony Fauci has talked about. But they are really at the beginning of this process. You still dont have an immunological correlate of protection; you still dont really have a dose. The forty-five people who are being tested in Washington state have been divided into three groups of fifteen and each given a different dose. They started with a low dose, then they moved to a middle dose, and now they are moving to a higher dose. But thats only fifteen people in each group. Really, to do this right, you would need thousands of people to make sure you are giving the right dosenot too much or too little. I presume that they will move to that, but it takes time.

Heilbrunn: What is a realistic timeline for a vaccine?

Offit: You want to make sure that a vaccine induces an immune response that you think will be safe. Im assuming that they are not doing animal-model studies because it seems that they moved very quickly to human trials. It would have been nice to do animal-model studies. While mice arent bad, they do give you hints to what could be potential safety problems. But it looks like that is not happening.

When you are where they are nowwhich is about forty-five people testedyou do need to gradually expand that to thousands of people at the dose you think youre looking at and make sure a significant percentage of the population is receiving that, and that that population represents the U.S. population. You want those people to develop an immune response that would protect them, even though you dont, right now, have immunological correlate protection. We dont know that, because we arent doing animal studies and we obviously arent doing human trial studies with this virus. Then you would need an efficacy trial, and that would best be done on healthcare workers.

Healthcare workers are the ones who are most likely to come in contact with COVID-19 patients, both by frequently being in contact and in close contact with them because they have to examine them. That would probably be the group with which to do an ethicaltrial, but that takes time. That takes years. For us, in the development of the Rotavirus vaccine, that took sixteen years before we got to the large, definitive, phase three trial. That was a placebo-controlled, prospective, eleven-country, four-year, $350 million trial, on 70,000 babies. That was a definitive phase three trial.

My sense is that they are moving along in this break the glass mode, which is to say that they will use fewer people in these studies and may bypass the FDA. They might just move to offer this. That said, to put this in perspective, Dr. Fauci is certainly right. The mRNA approach is very quickly scale-uppable. You can make very large numbers, remember you are talking about making billions, hundreds of millions of doses. But the mRNA still needs to be delivered in this complex lipid delivery system, which is not so easy to scale up. It could take a year to just scale up that part of it. And the filling takes time. Even if they use multi-dose vials, the filling alone could take a year. So, I dont see eighteen monthsDr. Fauci could see something I dont here, he is certainly closer to itbut I think eighteen months is a very, very, very optimistic timeline.

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Why A Coronavirus Vaccine May Be Years Away - The National Interest

Since the first reports of coronavirus (COVID-19) in Wuhan, China in December 2019 there have been more

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The race is on for coronavirus vaccines and treatments: current R&D status - The Pharma Letter

Disclaimer: This post is from GomerBlog, a satirical site about healthcare.

CDC officials announced Tuesday that they believe the new vaccine currently under development aimed at controlling the rapidly spreading SARS-CoV-2 virus -- responsible for causing COVID-19 -- will be approved and ready to be utterly rejected by those in the anti-vaccination (anti-vax) movement by next year.

"This is an exciting development," said Eric Polsky, director of the CDC's Novel Vaccination Program, "and we will work tirelessly to ensure all anti-vaxxers have the opportunity to decline, refuse, and reject this potentially life-saving vaccine as early as possible."

The announcement has many in the anti-vaccination movement excited, including a local woman present at the press conference, who noted, "I just get such a thrill from ignoring mountains of scientific evidence at the danger of threatening the world around me, and the chance to do that by yet again opting out of a critical vaccine is just delightful."

At press time, officials noted conspiracy theories about the not-yet-developed vaccine containing mercury were spreading on Twitter.

Last Updated March 31, 2020

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CDC: Coronavirus Vaccine Will Be Ready for Refusal By Anti-Vaxxers By 2021 - MedPage Today

The past few weeks have revealed the worst and the best in human responses to the coronavirus crisis from the supermarket hoarders clearing the shelves to the neighbourhood groups organising help for elderly and vulnerable people.

When it comes to the pharmaceutical companies, how should we judge their response? They, after all, hold the key to ending the pandemic. Yet in one vital respect their behaviour has more in common with the supermarket hoarders than the neighbourhood groups.

Our exit strategy from the global lockdown depends on the development of an effective vaccine, as is well-known. A huge effort is under way to find such a vaccine, but we cannot afford to wait the 18 months it might take.

In the meantime, as the death toll increases, doctors are desperate for treatments that would lessen the impact of the virus, by shortening the infection, reducing its severity and in that way saving lives. There is now a global hunt for a coronavirus drug. But it is a fight against time. The focus is therefore on existing treatments already proved to be safe for other diseases which will need less testing and be easier and quicker to manufacture in quantity.

Scores of trials are under way around the world. The World Health Organization has identified four of the most promising therapies including an HIV combination treatment, an anti-malarial and a drug developed but never used against Ebola - for testing in a global trial launched last month. But we cannot pause the search while waiting for the results. The need for new effective agents is too great.

The best way to identify candidate drugs is to use artificial intelligence (AI) to crunch huge quantities of data to find the ones that might work. Major AI companies are putting their immense computing power at the service of scientists engaged in this hunt.

But they are being hampered: because some pharmaceutical companies are failing to share all of the data on potential candidate treatments that they hold. Like toilet roll profiteers, they are keeping it stashed in their digital attics and cellars where others cannot get at it, on the grounds that it is commercially confidential.

It was the open sharing of data around the world that allowed scientists to map the genome of the SARS-CoV-2 virus at unprecedented speed, working across institutional, commercial and international boundaries in a unique collective effort against a common global enemy. We now urgently need all pharmaceutical companies to set aside their individual commercial ambitions and join a similar collective effort to identify, test, develop and manufacture treatments to curb the disease.

There is a precedent. Last June, 10 of the worlds largest pharmaceutical companies including Johnson & Johnson, AstraZeneca and GlaxoSmithKline announced they would pool data for an AI-based search for new antibiotics, which are urgently needed as antibiotic-resistant bacteria have proliferated across the world, threatening the growth of untreatable disease.

That historic agreement was made possible by the development of a secure, blockchain-based system that allows an algorithm to search rival companies data with full traceability but without revealing commercial secrets to competitors. The advantage of using blockchain is that companies can trust the code rather than their partners.

AI researchers at the Massachusetts Institute of Technologys J-Clinic, who trained a neural network to predict which molecules will have antibiotic properties, announced in February that they had found a new compound which works against 35 different types of bacteria. They named it halicin, after the AI system in 2001: A Space Odyssey.

AI is now being harnessed across the globe in the hunt for a coronavirus treatment, from Hong Kong to Israel to the UK and US. Last month the worlds fastest supercomputer, the IBM Summit, identified 77 compounds as potential candidates. Last week an AI platform run by Gero, based in Singapore, identified six drugs already approved for human use in other conditions which could help combat Covid-19. Meanwhile, Thomas Siebel, the billionaire head of C3.ai, a Californian artificial intelligence company, announced a public-private consortium including Princeton, Carnegie Mellon University, MIT, the Universities of California, Illinois and Chicago, as well as C3.ai and Microsoft, which will provide scientists with funding and access to some of the worlds most advanced supercomputers in the search for solutions to the pandemic.

However, no matter how great the computing power or how advanced the software design, results from these initiatives will depend ultimately on the data fed into them. Without full access to comprehensive data, the scientists will be fighting with one hand tied behind their backs.

All pharmaceutical companies must unlock their chemical libraries so candidate drugs can be identified, and trials to test the most promising treatments begin as soon as humanly possible. We cannot wait. Lives depend on it.

Prof Ara Darzi is a surgeon and director of the Institute of Global Health Innovation at Imperial College London. He is a former Labour health minister

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The race to find a coronavirus treatment has one major obstacle: big pharma - The Guardian

Jennifer Haller receives the first administration of an mRNA vaccine, made by the biotech firm Moderna, against the pandemic coronavirus.

By Jon CohenMar. 31, 2020 , 5:15 PM

Sciences COVID-19 reporting is supported by the Pulitzer Center.

The coronavirus that for weeks had been crippling hospitals in her hometown of Seattle changed Jennifer Hallers life on 16 Marchbut not because she caught it. Haller, an operations manager at a tech company in the city, became the first person outside of China to receive an experimental vaccine against the pandemic virus, and in the days since, she has been flooded by an outpouring of gratitude. Theres been overwhelming positivity, love, and prayers coming at me from strangers around the world, Haller says. We all just feel so helpless, right? This was one of the few things happening that people could latch on to and say, OK, weve got a vaccine coming. Disregard that its going to take at least 18 months, but its just one bright light in some really devastating news across the world.

The vaccine Haller volunteered to test is made by Moderna, a well-financed biotech thathas yet to bring a product to market. Moderna and Chinas CanSino Biologics are the first to launch small clinical trials of vaccines against coronavirus disease 2019 (COVID-19) to see whether they are safe and can trigger immune responses. (The CanSino vaccine trial also began on 16 March, according to researchers from the Chinese militarys Institute of Biotechnology, which is collaborating on it.) An ever-growing table put together by the World Health Organization now lists 52 other vaccine candidates that could soon follow. This is a wonderful response from the biomedical community to an epidemic, says Lawrence Corey, a virologist at the Fred Hutchinson Cancer Research Center who has run vaccine trials against a dozen diseases but is not involved with a COVID-19 effort. Its both gratifying and problematic in the sense of how do you winnow all this down?

Broadly speaking, these vaccines group into eight different platformsamong them old standbys such as inactivated or weakened whole viruses, genetically engineered proteins, and the newer messenger RNA (mRNA) technology that is the backbone of the Moderna vaccineand their makers include biotechs, academia, military researchers, and a few major pharmaceutical companies. On 30 March, Johnson & Johnson (J&J) announced what it said could bea $1 billion COVID-19 vaccine project, with about half the money coming from the U.S. Biomedical Advanced Research and Development Authority if milestones are met.

Many viruses, including HIV and hepatitis C, have thwarted vaccine developers. But the new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), doesnt appear to be a particularly formidable target. It changes slowly, which means its not very good at dodging the immune system, and vaccines against the related coronaviruses that cause SARS and Middle East respiratory syndrome (MERS) have worked in animal models. Corey heads the United Statess HIV Vaccine Trials Network, which has seen one candidate vaccine after another crash and burn,is optimistic about a SARS-CoV-2 vaccine. I dont think this is going to be that tough.

One concern is whether people develop durable immunity to SARS-CoV-2, which is crucial given that vaccines try to mimic a natural infection. Infections with the four human coronaviruses that typically cause minor colds dont trigger long-lasting immunity. Then again, researchers have found long-lasting immune responses to the viruses causing SARS and MERS, and genetically they are far more like SARS-CoV-2. And unlike cold-causing viruses, which stay in the nose and throat, the new coronavirus targets the lower respiratory tract, where the immune response to a pathogen can be stronger, says Mark Slifka, an immunologist who studies vaccines at the Oregon National Primate Research Center. When you get an infection in the lungs, you actually get high levels of antibodies and other immune cells from your bloodstream into that space.

Even with this all-out effort, Anthony Fauci, director of the U.S. National Institute of Allergy and Infectious Diseases (NIAID), predicts getting a vaccine to the public is going to take a year, a year and a half, at least. And Fauci adds at least because side effects, dosing issues, and manufacturing problems can all cause delays. Already some are calling for an ethically fraught shortcut to speed up clinical trials: giving people candidate vaccines and then intentionally attempting to infect them to see whether theyre protected.

A new vaccine might also be made available to health care workers and others at high risk even before phase III efficacy trials are completed. And Stanley Perlman, a veteran coronavirus researcher at the University of Iowa, suggests a vaccine that only offers limited protection and durability could be good enoughat first. In this kind of epidemic setting, as long as you have something that tides us along and prevents a lot of deaths, that may be adequate, he says.

On 13 January, 3 days after Chinese researchers first made public the full RNA sequence of SARS-CoV-2, NIAID immunologist Barney Graham at sent Moderna an optimized version of a gene that would become the backbone of its vaccine. Sixty-three days later, the first dose of the vaccine went into Haller and other volunteers participating in the small trial at the Kaiser Permanente Washington Health Research Institute. In 2016, Graham had made a Zika virus vaccine that went from lab bench to the first volunteer in what he then thought was a lightning-fast 190 days. We beat that record by nearly 130 days, he says.

The effort benefited from lessons Graham learned from his past vaccine efforts, including his work on respiratory syncytial virus (RSV). The search for an RSV vaccine has a checkered past: in 1966, a trial of a candidate vaccine was linked to the death of two children. Later studies identified the problem as vaccine-triggered antibodies that bound to the surface protein of the virus but did not neutralize its ability to infect cells. This antibody-viral complex, in turn, sometimes led to haywire immune responses.

The World Health Organization has tallied dozens of vaccine candidates, based on a variety of technologies. Two have started human safety trials (*).

Studying the 3D structures of the RSV surface protein, Graham discovered that the dynamic molecule had different orientations before and after fusing with the cell. Only the pre-fusion state, it turned out, triggered high levels of neutralizing antibodies, so in 2013 he engineered a stable form of the molecule in that configuration. It was so clear at that point that if you didnt have structure, you didnt really know what you were doing, Graham says. An RSV vaccine that built on this concept hasworked wellinearly trials.

The experience came in handy in 2015, when a member of Grahams lab made a pilgrimage to Mecca, Saudi Arabia, and came back ill. Worried that it might be MERS, which is endemic in Saudi Arabian camels and repeatedly jumps into humans there, Grahams team checked for the virus and instead pulled out a common cold coronavirus. It was relatively easy to determine the structure of its spike, which then allowed the team to make stable forms of the spikes for the SARS and MERS viruses, and, in January, for SARS-CoV-2s. Thats the basis of the Moderna COVID-19 vaccine, which contains m RNA that directs a persons cells to produce this optimized spike protein.

Still a new strategy, no mRNA vaccine has yet reached a phase III clinical trial, let alone been approved for use. But producing huge numbers of vaccine doses may be easier for mRNA vaccines than for traditional ones, says Mariola Fotin-Mleczek of the German company CureVac, which is also working on mRNA vaccine for the new coronavirus. CureVacs experimental rabies vaccine showed a strong immune response with a single microgram of mRNA. That means 1 gram could be used to vaccinate 1 million people. Ideally, what you have to do is produce maybe hundreds of grams. And that would be enough, Fotin-Mleczek says.

Many companies are relying on time-tested techniques. Sinovac Biotech is making a SARS-CoV-2 vaccine byinactivating whole virus particles with formaldehyde and adding an immune booster called alum. Sinovac used the same strategy for a SARS vaccine it developed and tested in a phase I clinical trial 16 years ago, says Meng Weining, a vice president at Sinovac. We immediately just restarted the approach we already know. The companys SARS vaccine worked in monkeys and although there were concerns that an inactivated coronavirus vaccine might trigger the sort of antibody enhancement disease that occurred with the RSV vaccine, Meng stresses that no such problems surfaced in their animal studies.

Florian Krammer, a virologist at the Icahn School of Medicine at Mount Sinai, says inactivated virus vaccines have the advantage of being a tried-and-true technology that can be scaled up in many countries. Those manufacturing plants are out there, and they can be used, says Krammer, who co-authored a status report about COVID-19 vaccines that appears online inImmunity.

CanSino is now testing another approach. Its vaccine uses a nonreplicating version of adenovirus-5 (Ad5), which also causes the common cold, as a vector to carry in the gene for the coronavirus spike protein. Other vaccine researchers worry that because many people have immunity to Ad5, they could mount an immune response against the vector, preventing it from delivering the spike protein gene into human cellsor it might even cause harm, as seemed to happen in a trial of an Ad5-basedHIV vaccine made by Merck that was stopped early in 2007. But the same Chinese collaboration produced an Ebola vaccine, which Chinese regulators approved in 2017, and a company press release claimed its new candidate generated strong immune responses in animal models and has a good safety profile. I think pre-existing Ad5 immunity and HIV vaccine risk are not a problem, Hou Lihua, a scientist working on the project at the Institute of Biotechnology, wrote in an email to Science, noting that the Ebola vaccine trial results adds to their confidence that these will not be issues.

Disregard that [a vaccine is] going to take at least 18 months, but its just one bright light in some really devastating news across the world.

Other COVID-19 vaccine platforms include a laboratory-weakened version of SARS-CoV-2, a replicating but harmless measles vaccine virus that serves as the vector for the spike gene, genetically engineered protein subunits of the virus, a loop of DNA known as a plasmid that carries a gene from the virus, and SARS-CoV-2 proteins that self-assemble into viruslike particles. J&J is using another adenovirus, Ad26, which does not commonly infect humans, as its vector. These different approaches can stimulate different arms of the immune system, and researchers are already challenging vaccinated animals with SARS-CoV-2 to see which responses best correlate with protection.

Many researchers assume protection will largely come from neutralizing antibodies, which primarily prevent viruses from entering cells. Yet Joseph Kim, CEO of Inovio Pharmaceuticals, which is making a DNA COVID-19 vaccine, says a response by T cellswhich clear infected cellsproved a better correlate of immunity in monkey studies of the companys MERS vaccine, which is now in phase II trials. I think having a balance of antibody and T cell responses probably is the best approach.

Kim and others applaud the variety of strategies. At this early stage, I think it makes sense to try anything plausible, he says. As Stephan Bancel, CEO of Moderna, says, Nobody knows which vaccines are going to work.

Spurring many of the efforts in the nascent COVID-19 field has been the Coalition for Epidemic Preparedness Innovations (CEPI), a nonprofit set up to coordinate R&D for vaccines against emerging infectious diseases. So far, CEPI has invested nearly $30 million in vaccine development at Moderna, Inovio, and six other groups. We have gone through a selective process to pick the ones that we think have the greatest likelihood of meeting our goalswhich we think ought to be the worlds goalsof speed, scale, and access, says CEPI CEO Richard Hatchett.But he is rooting for other candidates as well. We dont want to be in a situation where we have [one] successful vaccine and we have a contamination event [during manufacturing] and suddenly we dont have any vaccine supply.

CEPI invests in manufacturing facilities at the same time it puts money into staging clinical trials. By doing things in parallel rather than in serial fashion, we hope to compress the overall timelines, Hatchett says. After reviewing phase I data and animal model data, CEPI plans to move six of the eight products into larger safety studies to arrive at three that are worthy of full-scale efficacy trials that enroll perhaps 5000 participants.

CEPI has less than $300 million in its coffers for the effort, and Hatchett estimates the price tag at $2 billion. He says CEPI hopes to raise this money from governments, private philanthropies, industry, and the United Nations Foundation.

Seth Berkley, who heads Gavi, the Vaccine Alliance, arguedin an editorial in the 27 March issue ofSciencethat the world needs to come together even more to streamline the search for a COVID-19 vaccine. If ever there was a case for a coordinated global vaccine development effort using a big science approach, it is now, Berkley wrote, stressing that there must be extraordinary sharing of data, coordination of clinical trials, and funding. You cant move 100 vaccines forward, he says.

Moderna and J&J both say that if everything goes perfectly, they could launch an efficacy trial with about 5000 people by late November and determine by January 2021 or so whether the vaccine works. Meng says that, depending on approval from Chinese regulatory agencies, Sinovac could move its vaccine through small phase I and II tests by June. But, because of Chinas success at controlling its epidemic, the company may have to find another country that has high transmission of SARS-CoV-2 to stage an efficacy trial quickly.

Haller has had no serious side effects from the mRNA injected into her arm but realizes that the phase I study will not determine whether the vaccine is effective. The chances of the one that I got being really anything? I dont know, Haller says. This is just the first of many, many vaccines, and its just stupid luck that I was the first one.

With reporting by Kai Kupferschmidt.

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With record-setting speed, vaccinemakers take their first shots at the new coronavirus - Science Magazine

The devastation that coronavirus is causing around the globe will come to an end, but the questions on everyones lips is 'how' and 'when'. Despite strategies deployed to contain and limit the spread of the disease, the answer to the first part of the question is with the introduction of a vaccine. The second part regarding a timescale is at best an estimation.

Numerous companies across the globe are attempting to find a workable vaccine, and progress has been aided by the sharing of early information on the virus by China. The analysis that has followed in laboratories has advanced at pace, with studies into just how Sars-CoV-2 infects human cells. It is believed that there are already at least four organisations with potential vaccines, which are being tested on animals to see the effects. One, by American company Moderna, is expected to enter human trials very soon.

It may not feel like it to the average person who is suffering through the current situation, but scientists have had a head start on finding a solution to Covid-19. We have, in recent memory, experienced other coronavirus epidemics - with Sars in China (2002-04) and Mers from Saudi Arabia (2012) - and the work being done on a vaccine now builds on the back of that done then and put to one side.

Picture shows containers for the samples taken to drivers at a drive-through testing point for the COVID-19 disease at the University Hospital in Burgos.CESAR MANSO(AFP)

Human clinical trials take time. First the vaccine must be checked for safety, then for effectiveness to a group of a few hundred, and finally in a much larger group. Jumping ahead of this process - which can be tempting given the large number of people dying on a daily basis - is not prudent and this is why having a decent batch of candidates is important. Many of them will fail at one of the stages, and the hope is that one of them passes through to final approval.

Despite the blindly optimistic claims from US President, Donald Trump in early March, vaccines have sometimes taken decades to reach that approval stage. The general advice from the experts in this field suggest that around 18 months will be required. That takes us to the summer of 2021, quite some distance away, but a relatively speedy delivery in the world of vaccinologists.

Sin tituloA researcher works on the development of a vaccine against the new coronavirus COVID-19, in Belo Horizonte, state of Minas Gerais, Brazil.DOUGLAS MAGNO(AFP)

And having a vaccine approved is sadly not the end of the process. Political and economic challenges can make it a complicated to get the vaccine out to the many millions who require it. Often countries prioritise their key workers, like those in healthcare, as well as the defined at risk groups of the population. Richer countries tend to use their financial muscle too, meaning others can lose out relatively.

Providing people with an accurate date therefore of when a vaccine for Covid-19 will be ready for them to be administered is impossible. The belief is that we will come out of the worst of this, and possibly go through another spell at least, before one is ready for the general population. Clearly, there is an abundance of work being done to have it available as soon as it can be. Until then, the general advice of isolation, distancing, hygiene, etc, as well as the introduction of mass testing, must be followed to keep the spread in check.

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Coronavirus: when will the vaccine be ready? - AS South Africa

The biopharmaceutical industry will be able to make a Covid-19 vaccine probably a few of themusing various existing vaccine technologies. But many people worry that Covid-19 will mutate and evade our vaccines, as the flu virus does each season. Covid-19 is fundamentally different from flu viruses, though, in ways that will allow our first-generation vaccines to hold up well. To the extent that Covid does mutate, its likely to do so much more slowly than the flu virus does, buying us time to create new and improved vaccines.

Every virus has a genome composed of genetic material (either RNA or DNA) that encodes instructions for replicating the virus. When a virus infects a cell, it accesses machinery for making copies of its genomic instructions and follows those instructions to make viral proteins that assemble, with copies of the instructions, to form more viruses (which then pop out of the cell to infect new cells, either in the same host or in someone new).

There is a critical difference between coronaviruses and flu. The novel coronavirus genome is made of one long strand of genetic code. This makes it an unsegmented viruslike a set of instructions that fit on a single page. The flu virus has eight genomic segments, so its code fits on eight pages. Thats not common for viruses, and it gives the flu a special ability. Because the major parts of the flu virus are described on separate pages (segments) of its genome, when two different flu viruses infect the same cell, they can swap pages.

Imagine two people with eight-page reports fighting over a copy machine. In the tussle, some copies might turn out to have a mix of pages from two different reports. This page-swapping process, where viruses exchange parts of their genome, is called reassortment. The flu can change rapidly when multiple strains pass through the same host. But coronavirus, as a one-page report, tends to stay together, and while coronaviruses can swap sectionsin a process known as recombinationit is difficult to achieve and thus rare. (Imagine two pages ripping in the same way and swapping pieces that get glued together again.)

Coronavirus does mutate. All viruses mutate, in a way that can be likened to typos introduced by the copying process. Instead of a copy machine, imagine that a page of text is read by a scanner that then attempts to transcribe the words into a text file. The scanner may transcribe a page of text imperfectly, introducing a I for a l, and when thats printed out and then scanned again, the scanner makes more transcription mistakes on top of the old ones. After many cycles, the accumulating mutations in the code cause features of the virus to change gradually, a process called drift. When flu virus swaps entire pages with a different flu virus in a reassortment, we call that shift. Drift through typos tends to cause small changes. Shift through reassortment causes bigger ones.

A vaccine is like a description of a wanted criminal: it tells your immune cells whom to look out for. So long as the suspects appearance doesnt change too much, then the vaccine works. To the extent that the flu virus we see one year is only slightly different than the ones weve seen in recent years, our immune systems are at least partially prepared, and so we are partly protected. Even if we do get infected, it might be a milder illness because our immune system can react more quickly to fight it off.

Laboratories around the world are constantly surveilling todays flu strains and giving flu-vaccine manufacturers a heads-up as to what the viruses look like. So if we see a new strain of flu in Asia, its probably a good idea to start making a vaccine against it for the U.S. before that strain comes to our shores. Because large-scale manufacturing of current flu vaccines takes about six months from the time when we spot a new flu strain, the vaccines are six months out of date by the time we get them. Some years, the flu swaps out a genomic page with a less familiar strainmaybe one we havent seen for a decade or soand we get the vaccine wrong. When that happens, we suffer through a bad flu season, since our immune systems are less ready to fight it off.

In the worst case, the flu can suddenly pick up a page from a bird- or pig-flu strain to which most humans have had zero exposure. This can be far more deadly, because the new virus can evade our herd immunity entirely, cutting through the population unopposed. Thats a flu pandemic.

Todays novel coronavirus was brewing within bats for a long time, mutating into its current form through various typos and, to a lesser extent, rare recombination events among coronaviruses. Now that its here, its as new to us as a shifted flu strain that weve never seen before, and its causing a pandemic. But once weve developed a vaccine for this strainand once weve all taken itwell have herd immunity to it.

That immunity may fade as our immune system forgets the picture that the vaccine showed it, but we can solve that by getting booster shots of the same Covid-19 vaccine periodically. What we dont have to worry about is the virus rapidly mutating away from our vaccines as fast as flu can, because owing to its simplicity, it cant pull off the flus face-swapping tricks.

We hear reports that the novel coronavirus is already mutating into new strains, but these mutations are minor, and theyre unlikely to add up to anything significant. Even identical human twins have many genetic differences between them, but we still think of them as identical. In the case of Covid-19, very few of the changes weve seen so far would affect a vaccine. But if such changes do accumulate over time, our vaccine programs will be able to keep up.

Think of it this way: if flu evolves with the speed of a growing vine, then coronavirus is like a cactus. If you look very closely, a cactus can appear to be changing from day to day, but its nothing like a vine.

Were now inventing new vaccines from scratch and could plausibly go from nothing to a marketed vaccine in about a year. If laboratories around the world detect that this coronavirus is changing gradually, well most likely have time to match new strains before they change enough to cause a new outbreak. Rest assured: a vaccine is coming, it will work, and it will continue to work for as long as humanity must contend with Covid-19. Until then, we must maintain our social distancing so that our strained health-care system can keep up with the infections that we cant seem to prevent.

Peter Kolchinsky, a biotechnology investor and scientist, is Managing Partner of RA Capital Management, L.P., and author of The Great American Drug Deal.

Photo: Meyer & Meyer/iStock

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A Coronavirus Vaccine Is Coming, And It Will Work - City Journal

While many scientists are working on developing a coronavirus vaccine, others are busy testing antiviral drugs.

Vaccines are generally only effective when administered prior to infection, but antiviral agents are important because they can treat people who already have COVID-19.

Heres an overview of antiviral drugs scientists are investigating for coronavirus.

Read more: How does coronavirus kill?

How do antiviral drugs work? First, its important to understand the genome of animals and plants is composed of deoxyribonucleic acid (DNA), but viral genomes can also be comprised of ribonucleic acid (RNA). This is the case for SARS-CoV-2 coronavirus the virus that causes COVID-19.

In order to replicate, an RNA virus needs to make more copies of its RNA genome. This means antiviral drugs which block the copying of RNA genomes can potentially help treat COVID-19 patients. These drugs are known as RNA-polymerase inhibitors.

Read more: Here's why the WHO says a coronavirus vaccine is 18 months away

These types of drugs have successfully cured people of chronic hepatitis C another RNA virus infection.

But not all viral RNA polymerases are the same, so the drugs that work for hepatitis C virus will not necessarily work for human coronaviruses.

Favilavir is an RNA polymerase inhibitor drug scientists are currently trialling against coronavirus.

Another successful antiviral drug strategy is to use non-functional analogues, or inauthentic copies of the basic building blocks of the viral RNA genome. The presence of these analogues in the viral genome blocks the viral polymerase, meaning the virus cannot make another copy of its RNA. Acyclovir, ribavirin and azidothymidine (AZT) are examples of these drugs.

Unfortunately, this coronavirus is a bit tricky, because it proofreads the authenticity of its RNA genome. As such, it identifies the analogues as being inauthentic and removes them. This stops certain antiviral drugs like ribavirin from being effective.

Fortunately, the coronavirus proofreading powers dont block a similar drug, remdesivir. So remdesivir potently halts coronavirus replication and represents a promising drug option for COVID-19 patients.

Remdesivir is also effective against other RNA viruses including Ebola virus and the coronaviruses SARS and Middle Eastern respiratory syndrome (MERS).

Scientists are currently assessing remdesivir in clinical trials in the United States and China. Time will tell if remdesivir is effective for COVID-19 patients. But doctors are already considering how the drug is best administered for optimal results and whether it should be used in combination with other drugs or as a single agent.

Read more: COVID-19 treatment might already exist in old drugs we're using pieces of the coronavirus itself to find them

Many RNA viruses produce a single multi-protein thats later broken down into individual proteins via enzymes called proteases. Any molecules that inhibit these proteases have potential as antiviral drugs. Viral protease inhibitor drugs have been highly effective in treating the human immunodeficiency virus (HIV) and hepatitis C virus.

Lopinavir and ritonavir are a combination protease-inhibitor drug (Kaletra) that can inhibit coronaviruses in human cells. Kaletra has already been used to treat a patient with COVID-19 in South Korea, but a larger trial found its effects were unconvincing. The reasons for these discrepancies are currently unclear and more research is obviously needed.

With any antiviral drug, the sooner its administered once a patient is infected, the better the outcome. This is because viruses replicate quickly, producing tens to hundreds of new infectious viruses.

In respiratory infections caused by influenza or SARS-CoV-2 viruses, clinically serious infection involves whats called a cytokine storm. Here, a strong immune response results in the production of high levels of inflammatory mediators: cytokines and chemokines.

These molecules recruit inflammatory cells to the site of the virus infection, for example, the lungs of patients with COVID-19. These cytokines and cells then fight the virus infection, but their presence also partly obstructs the air sacs where oxygen exchange occurs.

Researchers are now considering add-on therapies that partly limit the inflammatory response by blocking the effects of certain cytokines and chemokines. These add-on therapies include antibody-based drugs, such as tocilizumab that blocks the interleukin-6 cytokine receptor or leronlimab that blocks the chemokine receptor CCR5. When cytokine receptors and chemokine receptors are blocked then it matters less that there are high levels of cytokines or chemokines, because their effects are significantly minimised.

The good news is antibody-based drugs have minimal side effects, and have proved effective for many human chronic inflammatory diseases. Expanding these drugs for use in COVID-19 patients is therefore an attractive possibility. Although this would require caution for careful dosing, and these drugs would need to be co-administered together with an antiviral drug.

Chloroquine, a well-known anti-malarial drug, has also gained attention. One study tested it together with a broad-spectrum antibiotic azithromycin. While some COVID-19 patients in this small study recovered, other patients died (despite chloroquine treatment), and some patients ceased treatment for a variety of reasons including the severity of their symptoms.

Nevertheless, people are interested in how chloroquine and azithromycin might work for coronavirus. Chloroquine exhibits antiviral activity and is currently used to treat autoimmune diseases because it also has anti-inflammatory properties. Azithromycin is an antibiotic used to treat bacterial infections, but it, too, exhibits antiviral activity, including against rhinovirus that causes the common cold. Chloroquine might need to be given early after infection to be most effective against coronavirus.

Read more: Could chloroquine treat coronavirus? 5 questions answered about a promising, problematic and unproven use for an antimalarial drug

The World Health Organisation has announced a global clinical trial program testing possible COVID-19 treatments, including remdesivir, lopinavir/ritonavir, chloroquine, and certain antiviral cytokines.

The escalating number of coronavirus patients worldwide means alongside vaccine development, the focus must remain squarely on finding effective antiviral drugs that can treat those already seriously ill from SARS-CoV-2 infection.

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In the fight against coronavirus, antivirals are as important as a vaccine. Here's where the science is up to - The Conversation AU

Johnson & Johnson says it could have a COVID-19 vaccine available by early 2021 with the capability to produce as many as a billion doses. In a press release, the company says its planning to start clinical trials in September and has begun investing in a rapid production capability to make the vaccine at scale should it prove safe and effective. Johnson & Johnson began work on a possible vaccine in January and has now selected a lead candidate vaccine and two backups which will enter early production phases to prepare for the expected overwhelming demand. If early trials validate the companys vaccine, the company would need an emergency use authorization from the FDA to begin providing the vaccine.

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Johnson & Johnson Says It Could Have Coronavirus Vaccine Ready by Early 2021 - The Daily Beast