Science’s COVID-19 reporting is supported by the Pulitzer Center.
Operation Warp Speed, the Trump administration’s bid to deliver a COVID-19 vaccine faster than any previous vaccine, is both turning heads and raising eyebrows with a major new investment that promises to shave weeks off its already ambitious timeline.
Warp Speed’s earlier target of mass immunizations of Americans starting in November already had many scientists and public health officials wondering whether the clinical trials needed to assure that a vaccine for the new coronavirus was safe and effective before wide-scale use could possibly be completed in time. But in a 21 May press release, Warp Speed upped the ante when it announced an investment of up to $1.2 billion in a vaccine being developed by AstraZeneca, noting that the delivery of the first of at least 300 million doses should arrive in October.
Much of Warp Speed’s inner workings, including how it chooses vaccine candidates, takes place behind closed doors. But the compressed timeline and the scale of the investment—more than twice the size of commitments the United States made earlier to Johnson & Johnson and Moderna to develop other vaccine candidates—is leading to questions about both the candidate vaccine and the plans for its clinical trials. William Haseltine, a former Harvard University HIV/AIDS researcher who helped launch several prominent biotechnology companies and now is a philanthropist, calls the timeline “unrealistic” and doubts this vaccine, developed by researchers at Oxford University’s Jenner Institute, “has any advantage over other approaches.”
But Adrian Hill, who heads the Jenner Institute and runs the vaccine project with Sarah Gilbert, calls the funding “a real vote of confidence” that these “crazy guys in England” might be able to beat the 18-month timeline that Anthony Fauci, the top research scientist on the White House’s Coronavirus Task Force, and others have repeatedly outlined. “We would like to think that some of the pulling forward of the timeline was driven by us,” says Hill. And he thinks it may have spurred other vaccine makers to speed up their efforts. “If our vaccine fails and we’ve done that, we’ll be pretty pleased.”
The Oxford team launched a clinical trial of the vaccine, which contains a harmless chimpanzee adenovirus “vector” carrying the gene for the SARS-CoV-2 surface protein, in 1100 people in the United Kingdom on April 23. Three weeks later, U.S. researchers the team collaborated with published a study in monkeys that delivered encouraging preclinical news about the vaccine: It could reduce the amount of virus in the lungs of monkeys that were intentionally infected.
By this summer, the vaccine could move into a 30,000-person efficacy trial in the United States, according to the press release from the Department of Health and Human Services (HHS) that announced the new investment. The money comes from the agency’s controversy-mired Biomedical Advanced Research and Development Authority (BARDA).
AstraZeneca says in a press release that it’s gearing up to start delivering the Oxford vaccine in September—the U.K. government has announced that it’s first in line because it supported the Oxford group—and it has the capacity to supply a billion doses by an unspecified date in 2021. The company has inked deals with other funders who are committed to “the fair allocation and distribution of the vaccine around the world.”
Hill says his team’s ongoing clinical trial in the UK, although not particularly large, could build confidence in the vaccine’s worth as early as August, soon after the larger efficacy trial staged in the United States and a separate one in the UK have begun. That’s because of the unusual approach the team is taking in what they call a combined phase 1 and 2 trial, which typically only look for immune responses and safety. The UK trial gives half the study participants their COVID-19 vaccine while a control group receives a marketed meningococcal vaccine as a comparator. If more people become infected in the control group, that could signal the vaccine works. “We chose to try and get an efficacy readout before the pandemic waned in England,” says Hill.
Hill worries about a repeat of his experience in West Africa in 2016, when the disappearance of Ebola ended an attempt to test a vaccine his group had designed for that disease. “It’s a blindingly obvious problem: The good news is we’re beginning to run out of good trial sites to do vaccine efficacy studies–even the U.S. is plateauing,” he says. “You’re left with Brazil and maybe India and maybe Russia. In a month’s time, you’ll probably have one country that you can do an efficacy trial in and you’ll probably have two or three good clinical trials teams at most in that country. So guess what’s going to happen? People are going to fight for that site to get the vaccine tested before it runs out.”
Seth Berkley, who heads GAVI, the vaccine alliance, and also is helping to oversee an international, multibillion dollar COVID-19 vaccine development effort called Access to COVID-19 Tools Accelerator, says clinical trials of the Oxford vaccine may yield “an efficacy signal” by October but he doubts there will be enough data to satisfy regulators evaluating whether to license the product. “I don’t see how that could happen,” says Berkley. But he says, “assuming everything goes well” it is possible that a regulatory agency might grant what’s known as emergency use authorization for wide-scale use of the vaccine, and determine whether to give full approval later when more data is in. “It’s doable,” he says, adding that “it’s a very aggressive timeline.”
Pediatrician Paul Offit, a vaccine researcher at Children’s Hospital of Philadelphia, questions whether the United States can even complete a 30,000-person trial in this timeframe. “I cannot imagine how this can be done within six months,” says Offit, who helped develop a rotavirus vaccine tested in an efficacy trial that lasted four years. “I think if it happened in nine months that would be remarkably fast.”
Offit, who wrote a book about an infamous 1955 manufacturing accident of a polio vaccine that crippled that crippled hundreds of children, worries that the impending U.S. presidential election is driving Warp Speed to set unrealistic deadlines. “The thing that really upsets me is I’m trying to think what’s the month after October? Oh, right, November,” says Offit. “I think the current administration may say, ‘This is our October surprise, this is this is my gift to this country, look what we did.’” Offit sits on a committee that is organizing COVID-19 vaccine trials in the United States–the National Institutes of Health’s public-private Accelerating COVID-19 Therapeutic Interventions and Vaccines—and says members were not consulted about BARDA’s investment or the proposed clinical trial.
Offit’s also concerned that racing forward could lead to harm—side effects of vaccines often are detected only when a candidate moves from thousands to millions of people—or a mediocre vaccine. It could also fuel vaccine skepticism. “You just have to worry that something bad could happen, and there’s fragile vaccine confidence in this country right now.”
Haseltine says the monkey data published on the Oxford vaccine raise doubts about whether it will have much impact on the pandemic, an argument he made in a much discussed Forbes magazine column. He notes that the vaccinated monkeys still had the viable copies of the virus in their noses, which means they could continue to transmit the infection. “The effect seems to be not to prevent infection, but rather to prevent lung disease,” says Haseltine. He contends that an effective COVID-19 vaccine will have to prevent infection itself—so-called “sterilizing immunity”—which Sinovac, a Chinese company, has shown is possible with their candidate. (The most comprehensive results yet from a human trial of a COVID-19 vaccine candidate appeared today in the Lancet. That vaccine, made by China’s CanSino Biologics, was tested in a 108-person phase 1 study found that it appears safe and capable of stimulating several different immune responses.)
Hill says it’s unfair to compare the monkey studies of the Oxford and Sinovac vaccines. He notes that Vincent Munster, the monkey researcher at the U.S. National Institute of Allergy and Infectious Diseases who led the study of the Oxford vaccine, used far higher doses of virus to “challenge” the vaccinated animals than the Sinovac team used, and also gave it by more routes of infection.
Munster, who agrees with Hill, says their experiment “is a very good result for a vaccine designed to prevent disease.” Next generation vaccines may indeed offer more protection, he says, and he welcomes Haseltine’s reservations. “It is really good if the data are under a lot of scrutiny,” Munster says. But for now, he says, “the real proof will be in the clinical trial data and the data is what people should focus on.”