Zemoria Harvey, 77, receives her first dose of the EMT Sohei Yamaguchi COVID-19 vaccine at St. Mark’s Baptist Church in Long Beach on Wednesday, February 10, 2021. The mobile vaccine clinic focused on black elderly people as a way to help resolve participation in the city’s coronavirus inoculation program.
Brittany Murray | MediaNews Group | Long Beach Press-Telegram via Getty Images
Covid-19 vaccine makers are figuring out how to adjust their prescriptions for worrying viral mutations – and regulators are looking to the flu as a model if and when vaccines need an update.
“It’s not really something you can do overnight,” warned Richard Webby, who runs a World Health Organization flu center at St. Jude Children’s Research Hospital.
Viruses mutate constantly and the right combination of specific mutations is needed to escape vaccination. But studies are raising concern that first-generation Covid-19 vaccines may not work as well against a mutant that first appeared in South Africa as it does against other versions that circulate around the world.
The good news: many of the new Covid-19 vaccines are made with new, flexible technology that is easy to update. What’s more difficult: deciding whether the virus has mutated enough that it’s time to modify vaccines – and what changes to make.
“When do you pull the trigger?” asked Norman Baylor, a former head of vaccines at the Food and Drug Administration. “This is a moving target now.”
Flu offers a model
WHO and FDA are analyzing the global flu vaccine system to decide how to deal with similar decisions about Covid-19 vaccines.
The flu mutates much faster than the coronavirus and flu vaccines need to be adjusted almost every year. National centers around the world collect influenza viruses in circulation and track their evolution. They send samples to laboratories designated by WHO for more sophisticated “antigenic” tests to determine the strength of the vaccine. WHO and regulators agree on vaccine revenue of the year and manufacturers start work.
For Covid-19 vaccines, Webby said that a critical step is to establish a similar surveillance and testing network to signal the mutations that matter. Today, there is great geographic variability in tracking and testing mutated versions. For example, Britain tests the mutant viral genome more than the US
Three variants first discovered in Britain, South Africa and Brazil are of concern because of the combinations of mutations that make them more contagious.
On Sunday, US researchers reported an even different mutation found in seven variants that appeared in several states. No one yet knows whether this mutation makes the virus easier to spread, but the report, not yet examined by other scientists, calls for more research to find out.
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Just because a variant is more contagious does not mean that it will also be immune to vaccination. But the variant first identified in South Africa is causing concern. David Ho of Columbia University placed blood samples from people who received the Pfizer or Moderna vaccines on laboratory plates with the mutant virus. The antibodies produced by the vaccine still protected, but were much less potent.
The results of preliminary tests on two other vaccine candidates – from Novavax and Johnson & Johnson – soon confirmed these findings. Both are still protected, but were weaker when tested in South Africa, where this variant dominates, than when tested elsewhere. A much smaller test of the AstraZeneca vaccine in South Africa raised questions about its effect.
“If the virus were able to make one or two additional mutations, it could escape even more,” warned Ho.
The real red flag
If fully immunized people start being hospitalized with the mutant virus, “that’s where the line is crossed,” said Dr. Paul Offit, a vaccine specialist at Children’s Hospital of Philadelphia who advises the FDA.
This has not yet happened, but “we must prepare,” he added.
Moderna is about to explore an option: could a third dose of the original vaccine increase immunity enough to rule out some variants, even if it is not an exact match?
Columbia’s Ho said it’s a good idea to test why people can “still have a lot of cushioning” if their overall antibody levels are too high.
The leading manufacturers are also developing experimental variant vaccines, just in case.
Covid-19 vaccines produce antibodies that recognize the spike protein that lines the coronavirus. When the virus mutates, the peak protein is sometimes altered in key areas, so that 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 some harmless copies of the spike protein that trains immune cells. To update the vaccine, they can simply change the payload: exchange the original genetic code with mRNA for the mutated spike protein.
The AstraZeneca vaccine and the Johnson & Johnson injection, which are due to be launched soon, are made with cold viruses designed to introduce a peak protein gene into the body. Adjusting your vaccines requires the growth of cold viruses with the mutated gene, a little more complex than the mRNA approach, but not as laborious as reformulating old-fashioned flu vaccines.
The Novavax vaccine, also in the final testing phase, is made with a laboratory developed copy of the spike protein that can also be adjusted to match the mutations.
Testing 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 took many months.
Simply changing the recipe to better target virus mutations will not require repeat studies for thousands of people, said Dr. Peter Marks, FDA chief of vaccines to the American Medical Association recently.
The FDA is still finalizing the requirements, but Marks said the agency intends to “be very agile”. If an updated vaccine is needed, tests on a few hundred people would probably be enough to say whether it triggers a good immune response, he said.
But an even bigger question: if only a few places faced vaccine-resistant virus mutants, would the authorities want injections with only variants or vaccines that protect against two types in one injection? After all, flu vaccines protect against three or four different types at once.
Companies would first have to do some basic research to make sure that a variant-only version properly accelerates the immune system, said John Grabenstein of the Immunization Action Coalition, a former vaccine executive at Merck. So a combined shot would need further testing to make sure that there is an equal answer for both types.