The makers of COVID-19 vaccines are figuring out how to adjust their prescriptions against troubling virus mutations – and regulators want flu as a blueprint if and when the shots need an update.
“It’s not really something you can turn around overnight,” warned Richard Webby, who heads a World Health Organization flu center out of St. Jude Children’s Research Hospital.
Viruses are constantly mutating and it takes just the right combination of certain mutations to escape vaccination. But studies are raising concern that first-generation COVID-19 vaccines don’t work as well against a mutant that first emerged in South Africa as they do against other versions circulating around the world.
The good news: Many of the new COVID-19 vaccines are made with new, flexible technology that can be easily upgraded. What’s more difficult: deciding whether the virus has mutated enough so that it is time to adjust vaccines – and what changes to make.
“When do you pull the trigger?” asked Norman Baylor, a former chief of the Food and Drug Administration’s vaccine. “This is currently a moving target.”
FLU OFFERS A MODEL
The WHO and FDA are looking to the global flu vaccine system to decide how to make similar decisions about COVID-19 injections.
Influenza mutates much faster than the coronavirus and flu shots have to be adjusted just about every year. National centers around the world collect circulating flu viruses and monitor how they evolve. They send samples to WHO-designated laboratories for more advanced “antigenic” testing to determine the potency of the vaccine. The WHO and regulators then agree on the vaccine recipe for the year and the manufacturers get to work.
For COVID-19 vaccines, Webby said a critical step is to set up a similar surveillance and testing network to highlight the mutations that matter. Today, there is great geographic variation in tracking and testing of mutated versions. Britain, for example, is doing more testing of the changing viral genome than the US.
Three variants first discovered in Great Britain, South Africa and Brazil are of concern because of combinations of mutations that make them more contagious.
On Sunday, US researchers reported yet another mutation found in seven variants that showed up in different states. No one knows yet if this mutation spreads the virus more easily, but the report, not yet vetted by other scientists, calls for further research to find out.
HOW COVID-19 SHOTS ARE
The fact that a variant is more contagious does not mean that it is also insensitive to vaccination. But the variant first identified in South Africa is of concern. David Ho of Columbia University put blood samples from people who received the Pfizer or Moderna vaccines in lab dishes containing the mutated virus. Antibodies produced by vaccines still protected, but they were much less potent.
Preliminary test results from two other vaccine candidates – from Novavax and Johnson & Johnson – quickly supported those findings. Both are still protected, but were weaker when tested in South Africa, where that variant dominates, than when tested elsewhere. A much smaller trial of the AstraZeneca vaccine in South Africa has raised questions about its effect.
“If the virus could make a few more mutations, it could escape even more,” Ho warned.
THE REAL RED FLAG
When fully immunized people are hospitalized with a mutated virus, “the line is crossed,” said Dr. Paul Offit, a vaccine expert at the Philadelphia Children’s Hospital who advises the FDA.
That hasn’t happened yet, but “we need to prepare,” he added.
Moderna is about to explore one option: Could a third dose of the original vaccine boost immunity enough to ward off some variants, even if it’s not an exact match?
Columbia’s Ho said it’s a good idea to test because people “can still have plenty of kisses” when their overall antibody levels are very high.
CUSTOMIZE THE RECIPES
Major manufacturers are also developing experimental variant vaccines, just in case.
COVID-19 vaccines produce antibodies that recognize the spike protein that envelops the coronavirus. When the virus mutates, the spike protein sometimes changes in key areas, so that the antibodies produced by the vaccine have a harder time recognizing it.
The Pfizer and Moderna vaccines are made with a piece of genetic code called messenger RNA that tells the body how to make harmless copies of the spike protein that immune cells train. To update the vaccine, they can simply change the payload: replace the original genetic code containing mRNA with the mutated spike protein.
The AstraZeneca vaccine and Johnson & Johnson shot expected to be rolled out soon are made with cold viruses designed to sneak a spike protein gene into the body. Modifying their vaccines requires growing cold viruses with the mutated gene, slightly more complex than the mRNA approach, but not nearly as laborious as reformulating old-fashioned flu shots.
The Novavax vaccine, which is also being tested in the final stage, is made with a lab-grown copy of the spike protein that can also be modified to match mutations.
TESTING VACCINES 2.0
The first-generation COVID-19 vaccines have been tested on tens of thousands of people to make sure they work and are safe – research that has taken many months.
By simply changing the recipe to better deal with virus mutations, there is no need to repeat those studies in thousands of people, Dr. Peter Marks, the FDA’s chief of vaccinations, recently at the American Medical Association.
The FDA is still finalizing the requirements, but Marks said the agency plans to be “pretty nimble.” If an updated vaccine is needed, tests on a few hundred people will likely be enough to determine if it causes a good immune response, he said.
But an even bigger question: if there are only some places vaccine-resistant virus mutants, would the authorities only want variants or vaccines that protect against two species at once? After all, flu vaccines protect against three or four different types at once.
Companies should do some basic research first to make sure a variant-only version properly stimulates the immune system, said John Grabenstein of the Immunization Action Coalition, a former Merck vaccine manager. Then a combination shot should be tested more to make sure both types respond equally.
The Associated Press Department of Health and Science is supported by the Science Education Department of the Howard Hughes Medical Institute. The AP is solely responsible for all content.