Six months after announcing the $5 billion Project NextGen to develop treatments and vaccines that can “stay ahead of COVID-19,” the U.S. government has awarded 20 contracts that reveal what much of that sum will support. The Department of Health and Human Services (HHS) announced on 13 October that up to $1.2 billion will go to three vaccine developers aiming to develop better shots, adding to another $1 billion already awarded to companies that will test them in yearlong, 10,000-person clinical trials. Another half-billion will support development of monoclonal antibodies (mAbs) that can block SARS-CoV-2 infection.
Project NextGen is far from the all-hands-on-deck effort of the $18 billion Operation Warp Speed, launched in May 2020, that led to the first COVID-19 vaccines in record time. But Jennifer Nuzzo, director of the Pandemic Center at Brown University School of Public Health, says the program could “improve upon existing COVID vaccines and treatments [and] lead to discoveries that can help in our fight against other infectious diseases.”
Others say it will do too little to prepare the world for the next pandemic. “The worst thing we could do is leave people with the sense that this is going to be the solution to the future,” says Michael Osterholm, an epidemiologist at the University of Minnesota who was on a steering group of researchers that wrote a detailed R&D roadmap for vaccines that could protect against many coronaviruses, not just SARS-CoV-2. But, he concedes, “It’s a start.”
Current COVID-19 vaccines only prevent symptomatic disease for a few months and are even less effective at preventing infection. Among the new awardees hoping to do better are CastleVax and Codagenix, which have developed vaccine candidates that will be sprayed into the nose. The goal is to stimulate immunity at the mucosal membranes, a strategy that might prove better at thwarting SARS-CoV-2 than current shots. A third vaccinemaker, Gritstone bio, uses an injected formulation designed to protect against a broader range of current and future SARS-CoV-2 variants.
Each company will receive $300 million to $400 million but will only be paid if they hit milestones such as meeting regulatory requirements for the clinical trials. Florian Krammer, a virologist at the Icahn School of Medicine at Mount Sinai who co-invented the CastleVax vaccine, applauds the decision to award the money to startup companies pursuing the riskiest, most innovative research, rather than the Big Pharma vaccinemakers that Warp Speed favored. “It’s going to allow us to move forward,” Krammer says.
In contrast to the vaccines from Moderna and the Pfizer-BioNTech collaboration, which consist of strands of messenger RNA (mRNA), CastleVax and Codagenix use live viruses that can infect cells in mucosal membranes, which produce SARS-CoV-2 proteins. CastleVax stitches the gene for SARS-CoV-2 spike protein inside of Newcastle Disease virus, which does not harm humans. Codagenix uses a version of SARS-CoV-2 it has engineered to not cause disease but still stimulate the immune system.
Gritstone relies on mRNA. But unlike the mRNA in current vaccines, which codes for the SARS-CoV-2 surface protein, spike, Gritstone’s codes for both spike and regions of the virus that remain conserved across a wide range of coronaviruses. The goal is to trigger both antibodies specific to spike and T cells that work against a broad range of variants. The mRNA in the Gritstone vaccine also makes copies of itself in human cells after being injected, potentially producing large amounts of these viral pieces to generate a stronger immune response.
Whereas vaccines train the immune system to fight infections, mAbs do the work themselves, and a subset of NextGen awardees hope to recreate the success mAbs had early in the COVID-19 pandemic. Back then, the U.S. Food and Drug Administration authorized one mAb to prevent infection against SARS-CoV-2 and eight others to treat mild and moderate COVID-19 disease. But viral variants soon dodged the mAbs, and all are now off the pharmacy shelf.
Regeneron will receive the lion’s share of the money, $326 million, to develop a better mAb. The company says its candidate binds to a conserved region of the virus, reducing the risk that variants will escape its powers. ModeX Theraputics—whose scientific leaders include former National Institutes of Health Director Elias Zerhouni—is developing antibodies that aim to thwart variants by targeting several viral sites. Finally, Vir Biotechnology will attempt to deliver mAbs via mRNA technology, injecting the code for each antibody rather than the molecule itself. That would allow a simple shot of mRNA to take the place of a complex infusion, and ease the rapid redesign for a newly circulating variant.
Myron Cohen, an infectious disease specialist at the University of North Carolina who advises several companies that make mAbs, notes the drugs might provide better protection against infection than existing vaccines. “MAbs given every 6 months are just like vaccines except there’s no wishful thinking required,” Cohen says.
But others note that for now, mAbs are far more expensive than vaccines, limiting their use. “If you were investing in new production methodologies for rapidly producing inexpensive antibodies, that makes some sense to me,” says Mark Dybul, a former director of the Global Fund to Fight AIDS, Tuberculosis and Malaria. “But if you’re just making more antibodies that are going to cost $8000 an infusion, that's not going to do it.”
Dawn O’Connell, HHS’s assistant secretary for preparedness and response, says her team expects clinical trials for mAbs to begin this fall and tests of the vaccine candidates to start in the winter. O’Connell says the goal is “strengthening us for whatever the COVID-19 virus brings next.”
The remaining half-billion dollars in the NextGen funding announced so far will support development of innovative technologies such as skin patches to deliver vaccines, antiviral drugs that might work against a wide range of coronaviruses, and wearable sensors to detect infections. But Osterholm and others note that one ambitious approach is missing: vaccines that could protect against all future variants of SARS-CoV-2 as well as viruses in the same family that have yet to jump into humans. Other entities, such as the nonprofit Coalition for Epidemic Preparedness Innovations and the National Institute of Allergy and Infectious Diseases, have committed $250 million to several companies and academic groups to spur development of these pancoronavirus vaccines.
Few of those products have moved far enough in the development pipeline to earn a place in NextGen. And some experts see that as evidence that support is waning for higher risk R&D that could pay off the next time a pandemic virus emerges. “We’re in worse shape now than we were at the beginning of the pandemic, because there was a collaborative spirit of, We’re going to share information and share knowledge, and we’re going to get to the answer,” says Dybul, who participated in the Independent Panel for Pandemic Preparedness and Response. “Everyone’s back in their corners. And that’s very risky. Because everyone’s just going back to the way we did it before, and that’s not what we need to prepare for the next pandemic.”
