COVID-19 vaccine makers are figuring out how to adjust their prescriptions against worrying virus mutations, and regulators are looking for the flu as a plan if and when the shots need an update.
“It’s not really something that can turn the switch, do it overnight,” warned Richard Webby, who runs a World Health Organization flu center. St. John’s Children’s Research Hospital Jude.
Viruses are constantly mutating and the right combination of certain mutations is needed to escape vaccination. But studies worry that first-generation COVID-19 vaccines may not 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 manufactured with new, flexible technology that is easy to upgrade. What’s harder is deciding if the virus has mutated enough that it’s time to modify the vaccines and what changes need to be made.
“When do you pull the trigger?” asked Norman Baylor, former head of vaccines at the Food and Drug Administration. “This is a moving target right now.”
FLU OFFERS A MODEL
The WHO and the FDA are studying the global flu vaccine system to decide how to manage similar decisions about COVID-19 vaccines.
The flu mutates much faster than the coronavirus and flu vaccines have to be adjusted almost every year. National centers around the world collect circulating flu viruses and track how they evolve. They send samples to WHO-designated laboratories for more sophisticated “antigenic” tests to determine the strength of the vaccine. WHO and regulators agree on the vaccine recipe of the year and manufacturers get to work.
For COVID-19 vaccines, Webby said a critical step is to establish a similar network of surveillance and testing to mark the mutations that matter. Today, there is great geographical variability in tracking and testing mutated versions. For example, Britain does more testing for viral genome change than the US
Three variants first discovered in Britain, South Africa and Brazil are worrisome due to the combinations of mutations that make them more contagious.
On Sunday, U.S. researchers reported an even different mutation that was found in seven variants that have appeared in several states. No one still knows if this mutation facilitates the spread of the virus, but the report, which has not yet been reviewed by other scientists, urges further research.
HOW TO TAKE COVID-19 SHOTS
The fact that a variant is more contagious does not mean that it is also impervious to vaccination. But the variant first identified in South Africa raises concerns. David Ho, of Columbia University, put blood samples from people who received the Pfizer or Moderna vaccines on lab plates with the mutated virus. Antibodies produced by vaccines were still protected, but were much less potent.
Preliminary test results from two other vaccine candidates, Novavax and Johnson & Johnson, soon supported these findings. Both were still protected, but were weaker when tested in South Africa, where this 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 one or two additional mutations, it could escape even further,” Ho warned.
THE TRUE RED FLAG
If fully immunized people start getting infected with mutated viruses, “that’s when the line is crossed,” said Dr. Paul Offit, a vaccine expert at Philadelphia Children’s Hospital who advises the FDA.
That hasn’t happened yet, but “we should get ready,” he added.
Modern is about to explore an option: could a third dose of the original vaccine boost immunity enough to defend some variants even if it’s not an exact match?
Ho, from Columbia, said it’s a good idea to do tests because people can “still have a lot of pillow” if their overall antibody levels are very high.
RECIPE ADJUSTMENT
Leading manufacturers also develop experimental variant vaccines, just in case.
COVID-19 vaccines produce antibodies that recognize the ear protein that coats the coronavirus. When the virus mutates, the ear protein is sometimes modified in key areas, so that the antibodies produced by the vaccine have more difficulty recognizing it.
Pfizer and Moderna vaccines are made with a fragment of a genetic code called messenger RNA that tells the body how to make harmless copies of the spike protein that trains immune cells. To update the vaccine, they can simply change the payload: change the original genetic code with mRNA for the mutated ear protein.
The AstraZeneca vaccine and the Johnson & Johnson shot that is expected to develop soon are made with cold viruses designed to stick a spike protein gene into the body. Adapting their vaccines requires the growth of cold virus with the mutated gene, a little more complex than the mRNA approach, but not as laborious as reformulating the old-fashioned flu vaccines.
The Novavax vaccine also in the final phase tests is done with a laboratory copy of the ear protein that can also be modified to match the mutations.
TEST VACCINES 2.0
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.
Simply changing the prescription to better target virus mutations will not require repeating these studies in thousands of people, Dr. Peter Marks, head of vaccines at the American Medical Association, recently told Dr. Peter Marks.
The FDA is still finalizing the requirements, but Marks said the agency intends to “be quite agile.” If an updated vaccine is needed, probably a few hundred people would be enough to know if it elicits a good immune response, he said.
But an even bigger question: If only a few sites faced vaccine-resistant mutant viruses, would authorities want shots of only variants or vaccines that would protect against two types at once? After all, flu vaccines protect against three or four different types in a single shot.
Companies should first conduct some basic research to make sure an exclusive version of versions properly revitalizes the immune system, said John Grabenstein, a former Merck Vaccine executive at the Coalition for Action on Immunization. Then, to make a combination more proof would be needed to make sure that there is an equal response to both types.
___
The Associated Press Health and Science Department is supported by the Howard Hughes Medical Institute’s Department of Science Education. The AP is solely responsible for all content.