The manufacturers of COVID-19 vaccines are figuring out how to adapt their prescriptions against worrying virus mutations – and regulators want to consider flu a blueprint if and when the survey is needed.
“It’s not really something you can make a switch to, but overnight,” warned Richard Webby, who runs a World Health Organization flu center in St. Louis. Jude Children’s Research Hospital lei.
Viruses mutate constantly and it only takes the right combination of certain mutations to escape vaccination. But studies are concerned that first-generation COVID-19 vaccines do not work as well against a mutant that first emerged in South Africa as against other versions spread 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 that it’s time to change vaccines – and what changes need to be made.
“When do you pull the trigger?” asked Norman Baylor, a former vaccine chief for the Food and Drug Administration. “It’s a moving target right now.”
Flu presents a model
The WHO and FDA are investigating the global flu vaccine system to decide how to handle similar decisions on COVID-19 shots.
Influenza mutates much faster than the coronavirus, and influenza injections need to be adjusted about every year. National centers around the world collect circulating flu viruses and monitor how they develop. They send samples to laboratories designated by the WHO for more sophisticated “antigen” tests to determine vaccine strength. The WHO and the regulators then agree on the vaccine recipe of the year and manufacturers start working.
For COVID-19 vaccines, Webby said a critical step is the establishment of a similar monitoring and testing network to identify the mutations that are important. Today, there is great geographical variability in the tracking and testing of mutated versions. Great Britain, for example, does more the changing viromome than the US
Three variants first discovered in Britain, South Africa and Brazil are of concern due to combinations of mutations that make them contagious.
U.S. researchers reported Sunday that a still different mutation was found in seven variants that surfaced in several states. No one yet knows if this mutation will facilitate the spread of the virus, but the report, which has not yet been investigated by other scientists, calls for further investigation to find out.
HOW COVID-19 SHOTS
Just because a variant is more contagious does not mean it will be impervious to vaccination. But the variant that was first identified in South Africa is a cause for concern. Columbia University’s David Ho has put blood samples from people who gave the Pfizer or Moderna vaccines into laboratory dishes containing the mutated virus. Antibodies produced by vaccines are still protected, but they were much less potent.
The preliminary test results of two other vaccine candidates – from Novavax and Johnson & Johnson – soon supported these findings. Both are still protected, but were weaker when tested in South Africa, where the variant predominates, than when tested elsewhere. A much smaller test of the AstraZeneca vaccine in South Africa has raised questions about its effect.
“If the virus could make an additional or two mutations, it could escape even more,” Ho warned.
THE RIGHT RED FLAG
When people who are fully immunized with a mutated virus are admitted to hospital, ‘the border is crossed’, dr. Paul Offit, a pediatrician of the vaccine for Philadelphia who advises the FDA, said.
It has not happened yet, but ‘we have to get ready’, he added.
Modern is about to explore one option: can a third dose of the original vaccine boost immunity to ward off some variants, even if they are not exactly consistent?
Columbia’s Ho said it’s a good idea to test because people can “still have a lot of pillows” if their total antibody level is very high.
ADJUSTMENT OF THE RECIPES
Major manufacturers are also developing experimental vaccinations, just in case.
COVID-19 vaccines produce antibodies that recognize the vein protein that covers the coronavirus. When the virus mutates, the vein protein sometimes changes on key areas, making it harder for the vaccine-producing antibodies to recognize it.
The Pfizer and Moderna vaccines are manufactured with a piece of genetic code called messenger RNA, which tells the body how to make harmless copies of the protein that trains immune cells. To update the vaccine, they can simply change the payload: swap the original genetic code with mRNA for the mutated ear protein.
The AstraZeneca vaccine and the Johnson & Johnson shot, which is expected to roll out soon, are made with cold viruses designed to sneak a vein protein gene into the body. To adapt their vaccines, cold viruses with the mutated gene should grow, a little more complicated than the mRNA approach, but not nearly as cumbersome as reformulating old-fashioned flu shots.
The Novavax vaccine is also being tested in the final stages with a copy of the vein protein grown in the laboratory, which can also be adapted to suit mutations.
TEST SETTINGS 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.
By simply changing the recipe to better target virus mutations, it is not necessary to repeat these studies in thousands of people, said dr. Peter Marks, the FDA’s vaccine chief, recently told the American Medical Association.
The FDA is still finalizing the requirements, but Marks said the agency intends to be ‘fairly smart’. If an updated vaccine is needed, tests in a few hundred people will probably be enough to determine if it elicits a good immune response, he said.
But an even bigger question: if only some places faced vaccination-resistant virus mutants, would authorities want shots or just vaccinations that protect against two species in one sting? After all, flu vaccines protect against three or four different species in one shot.
Companies will first have to do basic research to make sure a version is only properly repaired for the immune system, says John Grabenstein, a former Merck vaccine manager, of the Immunization Action Coalition. Then a combination survey will need to be tested more to make sure there is an equal response to both types.
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