Companies won’t share COVID-19 injections, stalling future vaccine research | Science

The US government has tens of millions of unused doses of messenger RNA (mRNA) COVID-19 vaccines, routinely canceling shots as they pass their expiration dates. It’s a dismal reflection on recent vaccine adoption, but it’s also a serious hurdle for scientists testing and developing vaccines that could protect against future SARS-CoV-2 variants and the next pandemic. Developers need existing vaccines as a benchmark to compare against new candidates. But government contracts with vaccine manufacturers and the companies’ own policies prohibit the use of vaccines for research.

“At this point in the game, with millions of vaccines on the verge of being thrown away, it seems crazy,” says Nicole Lurie, US director of the Coalition for Epidemic Preparedness Innovations (CEPI). The situation is so dire that a startup has created knockoffs of the mRNA vaccines used to help researchers improve their formulations.

Most researchers working on next-generation vaccines hope to create products that stimulate broader immunity to protect people against all sarbecoviruses, a group that includes variants of SARS-CoV-2, SARS-CoV-1 and related viruses found in bats and other wild viruses. animals that could spread to humans. As part of the development process, the researchers want to compare their candidates in animal models to proven Moderna and Pfizer mRNA vaccines. They want to see how the immune responses to the candidates compare to the responses generated by current injections. They also want to give animals existing and experimental vaccines and “challenge” them with different variants of SARS-CoV-2.

CEPI, which aims to accelerate the development of vaccines, has invested $230 million in 13 such candidate vaccines. The National Institute of Allergy and Infectious Diseases (NIAID) has committed nearly $60 million to seven other university teams working on so-called pancoronavirus vaccine development, which has similar goals. Four groups supported by CEPI or NIAID said Science that long-standing difficulties in obtaining comparator vaccines have slowed their progress. “Acquiring these direct comparators was very challenging and difficult,” says In-Kyu Yoon, director of CEPI.

Neither NIAID nor the Biomedical Advanced Research and Development Authority, which purchased and distributes the Pfizer and Moderna vaccines, responded to Science‘s questions.

The original Pfizer and Moderna mRNA vaccine efficacy trials compared these vaccines to placebo injections. But when these products received emergency use authorizations in December 2020, they became the standard by comparison in all future efficacy trials. THE initial thrust for comparators came from developers who had COVID-19 vaccine candidates based on technologies other than mRNA, such as viral vectors or nasal delivery.

Now, researchers aiming for more broadly protective vaccines need comparators to improve the design of their own candidates. The Pfizer and Moderna vaccines are now fully approved by the Food and Drug Administration (FDA), a status that would generally allow researchers to purchase and study them. But due to the emergency response to the pandemic, the US government owns all the product and, by contract with the companies, cannot provide it for research purposes. The contracts specify that the vaccines can only be used to immunize humans and that violations could in theory create liability issues for the companies.

The original doses of the Pfizer and Modern vaccines, which contain the surface protein of the initial strain of SARS-CoV-2, have limited value as comparators: the two companies now make “bivalent” products that mix with a surface protein of the Omicron Variant. But they, too, are locked in under government purchasing agreements.

Companies could make their vaccines available. But Pfizer and Moderna would not discuss the issue with Science, although Pfizer has confirmed that its vaccine is not for sale in any private market. “We do not currently supply it directly to other research organizations, with the exception of certain government-funded research organizations, outside of our own targeted clinical development program,” the company said.

Philip Krause, who for 11 years served as deputy director of the FDA’s division that oversees vaccines, says he can understand why a company with vaccines on the market might look like it’s sharing them with a potential competitor. “But obviously this is something that goes against public health in a huge way,” says Krause, who left the FDA in 2021 and is now a vaccine consultant. “If they throw doses away, or if those doses can’t really be given to anyone anymore, that’s even worse.”

PrEP4All, a nonprofit organization advocating for better public health responses to the COVID-19 pandemic, published in April a very critical report based on a 6 month investigation that involved numerous stakeholders and review of government contracts. “This is an eminently solvable problem that must be solved now – before [a] new crisis,” concludes the report, titled Science held hostage.

Some have adopted workarounds. Duane Wesemann, an immunologist at Brigham and Women’s Hospital who is on one of NIAID’s multi-year grants to develop a pan-sarbecovirus vaccine, said that “after many requests have been denied on many fronts for many months” for comparators to use in mouse studies, his group resorted to outdated Pfizer mRNA vaccines. “It’s not ideal, but in mice the vaccine works very well,” says Wesemann.

In another compromise, Helix Biotech helped frustrated pancoronavirus researchers by creating generic versions of the Pfizer and Moderna vaccines using publicly available formulas. Helix’s customers include NIAID, which provides the comparators to the researchers it funds. Graham Taylor, who started Helix Biotech last year, says the labs have shown that their copycats trigger immune responses similar to the real McCoy.

Helix products cannot be used as comparators to help pan-sarbecovirus vaccines gain FDA approval. This will require the real thing. Krause says regulators might be satisfied if human trials show a pan-sarbecovirus vaccine triggers immune responses similar to those elicited by the best approved products available, a concept known as immunobridging. Or they could require developers to run head-to-head clinical trials that use reduction in mild COVID-19 disease as an endpoint. Either way, Moderna or Pfizer would have to authorize the use of their bivalent vaccines.

Although animal studies can test the extent of protection of a pan-sarbecovirus vaccine, delivering on their promise would require exposure to new variants or even new coronaviruses. This could only happen in effective real-world studies that take place after a new virus begins to spread.

Boxes of unused COVID-19 vaccines currently sitting in freezers point to yet another hurdle for pan-sarbecovirus vaccines, says Krause: “Who will think they need them?