CEPI warns of a major obstacle to the development of new Covid-19 vaccines

The world still needs more and better vaccines against Covid-19. But a major obstacle stands in the way of the development of new vaccines, along with the critical studies needed to determine how best to use these important tools, warned the Coalition for Epidemic Preparedness Innovations (CEPI) in a letter published Tuesday in the journal Nature.

Unless countries that have purchased doses of vaccine and companies that have used vaccines before agree to find ways to fix the problem, manufacturers following the first wave of producers might not be able to prove that their vaccines are working. Not only will this slow down efforts to vaccinate the planet, but it will block the development of next-generation vaccines, and it will hamper efforts to answer key public health questions, such as whether the booster with a different vaccine would generate better protection, or if give smaller – fractional – doses could protect more people faster.

The letter was signed by CEPI’s Director of Vaccine Research and Development, Melanie Saville.

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In an interview with STAT, the US director of CEPI, Nicole Lurie, said that the organization had been trying for months to break the deadlock, to no avail. ” We are going in circles. “

Part of the problem stems from the fact that at this point in the pandemic it is not considered ethical to test new vaccines against placebos; instead, they should be tested against one of the existing plans. But getting hold of licensed or licensed vaccines for study is nearly impossible; all available doses have been collected by countries anxious to vaccinate as many of their citizens as possible.

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The contracts for these doses contain rigid stipulations on how the vaccines can be deployed. Doses often need to be used in the country that made the purchase; when the Biden administration wanted to share AstraZeneca doses with Canada and Mexico in March, he lent the doses to bypass the restrictions. Contracts also often state that doses purchased are to be used for epidemic control, not research, Lurie said.

There is little benefit to companies in making doses of their vaccines available for study. With global demand greatly exceeding current supply, manufacturers can sell every dose they can make.

And there are potential drawbacks. If a clinical trial testing a new vaccine shows that it works better than the vaccine it was compared to, that does not help future sales of the comparator vaccine. Likewise, if a study showed that it would be better to use a different vaccine as a booster injection – called a heterologous booster – it could plans undermined by manufacturers like Pfizer and Moderna to sell third doses of their vaccines.

There are a lot of questions that need to be answered about how best to use Covid vaccines. And the only way to answer that is through studies – studies that would require doses of vaccines like Pfizer-BioNTech’s Comirnaty and Moderna’s Spikevax, as well as the Johnson & Johnson and AstraZeneca vaccines and vaccines made by companies. manufacturers outside of North America and Europe.

“Let it be the interval [between doses], whether it is a heterologous prime-boost [studies]whether it’s stimulation strategies, split dosing, whatever… you need a licensed vaccine ”to test against, Lurie said. “And we cannot have access to vaccines. This is the basic problem.

The problem should not be insurmountable. South Korean vaccine maker SK Bioscience recently announced that it is starting a Phase 3 trial of a vaccine it is developing in collaboration with vaccine giant GSK, which provides a booster compound called an adjuvant. The clinical trial will compare the SK vaccine to the AstraZeneca vaccine. SK Bioscience too product the AstraZeneca vaccine.

On the health policy front, so-called “mix-and-match” trials are being conducted in both the United States and Great Britain. The aim is to see if using two different vaccines is more effective than using the same vaccine for both the priming and booster doses.

The american trial, conducted by the National Institute of Allergies and Infectious Diseases, studies the combinations of three vaccines authorized for use in this country: Pfizer, Moderna and J&J vaccines. The UK trial, led by the University of Oxford, is studying combinations of the Pfizer, Moderna and AstraZeneca vaccines – all of which are licensed in Britain – as well as a vaccine made by Novavax, which is in the process of seeking authorization for use emergency response from the UK regulatory authorities.

But in both cases, trials are only conducted with vaccines that are authorized for use in the country in which the study is being conducted. This means questions that have global ramifications – for example, could some of the Chinese vaccines be more effective if boosted with a Pfizer, AstraZeneca or Novavax vaccine? – will not be answered by these studies. None of the Chinese vaccines have been authorized in the US or UK

Lurie said CEPI is prepared to fund some of these crucial studies, but “moving forward on any of these things depends on our getting a vaccine.”

The quantity of vaccine doses needed is not massive. A phase 3 trial of a new vaccine may require 20,000 doses of a comparator vaccine. A Phase 2 trial measuring immunogenicity – the levels of antibodies that vaccine doses generate – would require much less. The UK trial, called Com-COV2, gives just over 1,000 volunteers a third dose of a vaccine that differs from their original vaccination schedule. The US lawsuit is even smaller, involving around 150 people.

Lurie said the problem could be solved if countries purchasing vaccines change contracts with suppliers. A number initially indicated their will, she said, but progress stalled when they did the right amount of work.

“We have a global problem to solve,” said Lurie. “We’re stuck with the vaccines we have unless we can move forward.”