By Carolyn Kormann
On Monday, Donald Trump held a meeting in the White House to discuss his Administration’s response to covid-19, the novel coronavirus that has spread to every continent except Antarctica. At the time there had been more than a hundred and five thousand cases reported in at least eighty-three countries, leading to more than thirty-five hundred deaths. Seated around an oval table in the Cabinet Room were health experts from the Centers for Disease Control and Prevention, the Food and Drug Administration, and the National Institutes of Health, as well as pharmaceutical executives from Pfizer, Johnson & Johnson, Sanofi, and others. With more than a hundred cases already discovered in the U.S., which had resulted in six deaths (the virus has since infected nearly four hundred people in the U.S., and killed at least nineteen of them), Trump was concerned. But he was also confused, despite having had several previous briefings with the Administration’s top health officials. Grasping for some good news, he pressed the executives to deliver a vaccine within a few months, at which point Anthony Fauci, the longtime director of the National Institute of Allergy and Infectious Diseases (N.I.A.I.D.), spoke up. “A vaccine that you make and start testing in a year is not a vaccine that’s deployable,” he said. The earliest it would be deployable, Fauci added, is “in a year to a year and a half, no matter how fast you go.”
The virus seems to have been circulating in the United States, particularly in Washington State, for the past month, and more cases are expected. A person can be infected but asymptomatic, and therefore unknowingly infect other people. This limits the ability of public-health tools to contain its spread. Even still, a covid-19 vaccine developed, licensed, and manufactured at a global scale in twelve months would be an unprecedented, remarkable, even revolutionary achievement. No other vaccine has come close to being developed that quickly. The fastest effort to date was during the Zika outbreak, in 2015, when one was ready for testing in about seven months, but the epidemic fizzled out before an approved vaccine could be sent through clinical trials. At the meeting on Monday, Trump said, “I like the sound of a couple months better, if I must be honest.”
John Shiver, the global head of vaccine research and development at the multinational pharmaceutical company Sanofi, which is developing a covid-19 vaccine, was at the meeting with Trump. “There was some confusion there,” Shiver said, that certain officials did not understand that “being in people,” as in human trials, is not the same as having a product. Clinical trials are conducted on healthy people, which is inherently challenging. “You certainly don’t want a vaccine that can make it worse,” Shiver said. “There have been some vaccine candidates historically that could actually enhance the disease.” Sanofi is working with the United States Biomedical Advanced Research and Development Authority, a sort of biomedical darpa, to advance a covid-19 vaccine based largely on the vaccine candidate it had developed for sars. Shiver told me that the authority doesn’t expect to have anything ready for human trials until much later this year. “It’s difficult,” Shiver said, “to see how, even in the case of an emergency, a vaccine could be fully ready for licensure in a year and a half.”
The Coalition for Epidemic Preparedness Innovations (cepi), an Oslo-based nonprofit organization, was established at Davos, in 2017, to help the world prepare for a “disease X” pandemic. One of its aims is to dramatically hasten the process of vaccine development. To create a viable, scalable vaccine “takes vast amounts of funding and R. & D.,” Rachel Grant, the advocacy and communications director at cepi, told me. “It is a long and complex business. It’s all doable, science can meet the challenges, but there is lots of attrition” before any vaccine gets to the point of licensure. The problem is twofold. First, there may never be a market for a vaccine at the end of the development process, because the epidemic is contained, or never comes to pass. Then, traditionally, if there is an epidemic, it may take hold in a developing country where the costs of research and development cannot be recouped. “The resources and expertise sit in biotech and pharma, and they’ve got their business model,” Grant said. “They’re not charities. They can’t do this stuff for free.”
cepi, with funding from the government of Norway, the Gates Foundation, the Wellcome Trust, and several other countries (the United States is not among them), is trying to bridge the gap. The challenge of vaccine development is “what cepi was set up to solve,” Grant told me, “played out writ large in an episode like this.” Since the novel coronavirus emerged, cepi has ramped up its grant-making expenditures to more than nineteen million dollars. Two grant recipients—a Massachusetts-based biotech startup named Moderna and a lab at the University of Queensland, in Brisbane, Australia—have, remarkably, already developed a vaccine candidate that they will start testing in human trials in the next few months, and another biotech startup supported by cepi is not far behind. But, ultimately, to get three different vaccines through the final phase of clinical testing, Nick Jackson, cepi’s head of programs and innovative technology, told me, will require an estimated two billion dollars.
Barney Graham is the deputy director of the Vaccine Research Center, at the N.I.A.I.D., in Bethesda, Maryland, which is collaborating with Moderna and other academic labs on a possible vaccine. Graham is one of the world’s experts on the structure of viruses and how they interact with human cells to make us sick. In the seven years before the covid-19 virus appeared, one of Graham’s projects had involved understanding the mers coronavirus, in order to potentially develop a vaccine. (mers, which can be transmitted from camels to humans, has been contained to the Middle East, and seems to spread mostly in confined spaces, like hospitals.) “There’s several ways of delivering a protein to a human body that will make a vaccine-type response,” he told me. Certain proteins, when injected into a human, are antigenic, provoking the body’s immune system to create antibodies. Traditionally, proteins are made “in a microbrewery type of bioreactor,” Graham said—a common flu-virus vaccine, for instance, is grown in chicken eggs—and it “takes up to two years to get that protein ready. That is not fast enough if you’re in a pandemic situation.” Researchers have long been working on so-called vaccine-platform manufacturing technologies for future use. The idea is akin to creating a frozen-yogurt maker for vaccines—same machine, different flavors. With vaccine-platform technologies, the hope is that the way in which the vaccine is manufactured and delivered to the body—such as Moderna’s messenger-RNA (mRNA) technology—will transport any antigen and, therefore, theoretically protect against any infectious disease. “You can make the RNA in the same way, purify it in the same way, release it in the same way, and yet make many different proteins,” Graham said.
In Moderna’s case, the vaccine contains a synthetic version of mRNA. When injected into a muscle cell, the mRNA acts like a drill sergeant, ordering the cell to create a doppelgänger of one of the coronavirus’s surface proteins—known as “spikes,” which, together, decorate the surface of the virus, giving the appearance of a crown. The spike protein is only part of the virus and therefore won’t make a person sick. But it is a crucial component of how the virus infects a human cell. In a sense, the Moderna technology outsources the labor of building these spike proteins to our own bodies. Once our muscle cells follow the vaccine’s mRNA orders, and manufacture loads of these spike-protein doppelgängers, our immune system recognizes them as foreign objects and learns how to fight them by creating antibodies.
Moderna has done several different vaccine trials with its mRNA “platform,” a few in partnership with Graham and the Vaccine Research Center. Among other things, they have tested mers coronavirus vaccines in mice. (There are now, including covid-19, seven known coronaviruses that infect humans, and many more carried by animals; four of them circulate in the population and are responsible for common colds, and the other two are sars and mers.) “The early data we already have with the mice shows it is working the way it should,” Graham said. “If this was a virus from a different family, we would not be nearly as prepared.”
On the other side of the world, at the University of Queensland, Keith Chappell is working on what he and his two co-inventors call a “molecular clamp,” a different type of rapid-response vaccine platform, also funded in part by cepi. The molecular-clamp vaccine uses a more traditional method compared to what Moderna is making; its shot would already contain the spike protein. The big difference is that Chappell’s team has found a way to incorporate a lab-created polypeptide (or sequence of amino acids)—“the clamp”—into the spike protein, to insure that the protein remains stable, folded like origami, in precisely the right configuration, thereby provoking a strong, accurate immune response (i.e., lots of appropriate antibodies). After years of working in cell cultures (Chinese-hamster ovaries, or CHO, the standard mammalian cell line used in therapeutic biomedical research), Chappell’s team plans to start testing its vaccine on about a hundred healthy adult volunteers, and he estimates that a trial will begin sometime this summer. “It’s a terrifying prospect, what’s occurring currently,” Chappell told me, by phone, from his lab in Brisbane. “It’s a lot of weight on our shoulders, and a lot of pressure.”
Even if the virus wanes in the warmer months, as does influenza, it will have circulated in the population already, and could reëmerge in the fall. For now, although the total number of infections worldwide is unknown, experts estimate, crudely, that the virus has a mortality rate between 0.5 per cent and two per cent. The flu, which kills, on average, between twenty thousand and forty thousand people each year in this country alone, has a mortality rate of 0.1 per cent. “We’re still learning a lot about the virus, what we were all watching for, and what has emerged is that it is readily spread person to person in a community setting, more so than sars or mers,” John Mascola, the director of the Vaccine Research Center at the N.I.A.I.D., told me. “That is not surprising, but it is concerning. There is the potential for the virus to really establish itself in a human population, and not go away quickly.”
On Tuesday, Trump toured Mascola’s Vaccine Research Center, where about five hundred scientists are at work. (On Friday, the President signed an $8.3 billion emergency-aid package to counter the virus; some of the funds will go toward the Vaccine Research Center’s work.) Kizzmekia Corbett, the research fellow leading the covid-19 vaccine team, explained the basics of virology to Trump—a student whom she had not anticipated—and other researchers showed off jumbo models of the coronavirus’s spike protein as Trump looked on, nonplussed. “The environment here is one of a lot of excitement,” Mascola later told me. “It’s gratifying to be recognized by the leadership, but, honestly, a lot of what we do is not recognized at that kind of level, and that really doesn’t matter. We do what we do because of the love of the science and our commitment to public health.”
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