Science‘s COVID-19 reporting is supported by the Pulitzer Center.
When the news broke yesterday that Operation Warp Speed had selected five experimental COVID-19 vaccines to fast-track through testing and, potentially, mass-scale production, it was news even to some top scientists involved with the White House-led program. “It’s been so chaotic, and it’s not even transparent to those of us who are trying to help out,” says a source linked to Warp Speed who asked not to be named.
The New York Times reported that according to “senior officials,” the Trump administration program had chosen vaccines from Moderna, the University of Oxford /AstraZeneca, Johnson & Johnson, and Merck for the crash development program, which aims to have enough safe and proven product to vaccinate 300 million Americans by January 2021. The government’s Biomedical Advanced Research Development Authority (BARDA) had already singled out all four for what could amount to more than $2 billion in funding if they hit milestones. The fifth vaccine flagged by The New York Times is made by Pfizer, whose CEO, Albert Bourla, said on 28 May at a media briefing that the company doesn’t want funding from any government because “We believe we can move faster if we don’t have to involve a third party.
According to The New York Times, Warp Speed will give the chosen companies “access to additional government money, help in running clinical trials and financial and logistical support for a manufacturing base that is being built even before it is clear which if any of the vaccines in development will work.” A spokesperson for Warp Speed says it will make an official announcement on its latest vaccine shortlist soon but currently has no comment.
The New York Times article offered no rationale for the selections. But the move appeared to signal that Warp Speed had changed its initial plan of doing comparative studies of 14 vaccines it said last month that it had singled out from the more than 100 candidates in development at companies and universities. “It’s typical Operation Warp Speed, where everything is sort of cryptic and it’s unclear what they’re actually saying,” complains Peter Hotez, a vaccine researcher at the Baylor College of Medicine who is part of a team developing a COVID-19 vaccine. “What have these vaccines been chosen to do?”
Hotez notably is on the vaccine committee of a public-private partnership organized by the U.S. National Institutes of Health that will supposedly help Warp Speed run clinical trials of chosen vaccines. But he and several other members of this committee, called Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV), told Science that Warp Speed did not ask for their input in the selection. “We’re sort of like two parallel universes,” Hotez says.
BARDA has funded a fifth vaccine manufacturer, Sanofi, whose candidate was not included in this cut. “Why were they voted off the island?” Hotez asks. “It’s just odd. They’re asking us for advice, which we’re providing it, but we have no insight into the decisionmaking.”
Paul Offit, a vaccine researcher at Children’s Hospital of Philadelphia who is on the same committee, says Warp Speed appears to have selected vaccines based on manufacturing concerns, not because they stand out as the most promising scientific approaches. “They’re the ones that are first because in many ways they’re the fastest ones to make,” Offit says.
Offit also questions the lack of diversity in the five selected vaccines, which rely on just three different technologies. Two candidates exploit messenger RNA to produce the surface protein for SARS-CoV-2, the viral cause of COVID-19. Two engineer theoretically harmless adenovirus vectors, which can infect cells but do not copy themselves, to hold the gene for that same protein, known as a spike. One relies on a replicating vector, vesicular stomatitis virus (VSV), to do the same thing. “We don’t really know anything about the safety or efficacy of these vaccines yet,” Offit says. “Shouldn’t we broaden our chances?” (The 133 vaccines on the World Health Organization’s COVID-19 vaccine list use eight different platforms.)
Monkey studies of the Oxford/AstraZeneca vaccine have been published, but some researchers questioned how well it worked and noted that it produced relatively modest levels of the antibodies that can “neutralize” the virus. Moderna was heavily criticized for releasing partial data from a small human trial in a press release. Pfizer, Merck, and Johnson & Johnson have not published any animal or human data about their COVID-19 vaccines.
Hotez notes that only one of the three technologies reportedly chosen by Warp Speed has led to a vaccine currently on the market: a VSV-based Ebola vaccine approved 6 months ago. “If I were in charge, I would focus, one, mostly on candidates that have a proven track record of making it to licensure, and two, candidates that are going to achieve high titers of virus neutralizing antibodies.”
As part of the program’s official unveiling on 15 May, which included a Rose Garden ceremony with President Donald Trump, Warp Speed stated it had selected 14 candidates but did not name them. Science has learned that shortly before that announcement, the list actually had 18 candidates. In addition to these five selected, it included vaccines made by Sanofi, Inovio, Novavax, Medicago, the U.S. Army, British American Tobacco, Codagenix, Institut Pasteur/Themis, Vaxart, NantKwest, Geovax, Greffex, and the University of Queensland. These vaccines represented seven of the eight platforms.
Biotech entrepreneur Patrick Soon-Shiong’s company NantKWest is developing a vaccine that was on Warp Speed’s list of 14 candidates but did not make the final cut. “We have to be very careful about jumping into a decision not based on the full understanding of the science,” says Soon-Shiong, whose vaccine aims to produce a stronger immune response by including a second protein along with spike. He also wonders why Warp Speed isn’t looking at an inactivated virus preparation, a tried-and-true platform that is the basis of many marketed vaccines. “That is a big question,” he says.
Inactivated, whole SARS-CoV-2 is the basis of four of the 10 vaccines that have advanced to human trials around the world, including one that worked well in a monkey study. But all four are made in China. As Science revealed earlier, Warp Speed explicitly would not consider any vaccines made in China.