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COVID-19 Vaccine Update: Shots may be tweaked if variants worsen

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COVID-19 vaccine makers are looking for ways to fine-tune their recipes for mutations in the virus of concern. Regulators want to get the flu as a blueprint when shots need to be updated.

“It’s not something you can switch on and do overnight,” warned Richard Webby, head of the World Health Organization’s Influenza Center at St. Jude Children’s Research Hospital.

The virus is constantly mutating and requires the appropriate combination of specific mutations to avoid vaccination. However, studies have raised concerns that first-generation COVID-19 vaccines will not work well against the first mutants that emerged in South Africa and against other versions distributed around the world. I will.

Good news: Many of the new COVID-19 vaccines are made with new flexible technologies that are easy to upgrade. Difficulty: Decide if the virus has mutated enough to change the vaccine and what changes to make.

“When do you trigger?” Asked Norman Baylor, a former Food and Drug Administration vaccine director. “This is currently a moving target.”

Influenza provides a model

The WHO and FDA are looking to the global influenza vaccine system in deciding how to handle similar decisions regarding COVID-19 shots.

Influenza mutates much faster than the coronavirus, and influenza vaccination needs to be adjusted almost every year. National centers around the world collect circulating influenza viruses and track how they are evolving. They send samples to WHO-designated laboratories for more sophisticated “antigen” tests to determine vaccine strength. WHO and regulators then agree on the vaccine recipe for the year and the manufacturer begins work.

For the COVID-19 vaccine, Webby said an important step is to establish a similar monitoring and testing network to flag critical mutations. Today, there is geographical variability in tracking and testing mutated versions.For example, the United Kingdom is testing a more changing viral genome than the United States.

The three variants first discovered in the United Kingdom, South Africa and Brazil are worried because of the combination of mutations that make them more contagious.

On Sunday, US researchers reported even more different mutations found in seven variants that occurred in several states. No one yet knows if this mutation facilitates the spread of the virus, but reports that have not yet been scrutinized by other scientists are urging further research to find it.

How COVID-19 Shots Hold Up

Just because a mutant is more contagious does not mean that it is impervious to vaccination. However, the first subspecies identified in South Africa raises concerns. David Ho of Columbia University placed blood samples of people vaccinated with Pfizer or Moderna in a laboratory dish with the mutated virus. The antibodies produced by the vaccine are still protected, but they were much less potent.

Preliminary test results from two other vaccine candidates from Novavax and Johnson & Johnson quickly confirmed their findings. Both are still protected, but when tested in South Africa, where the variant predominates, they were weaker than when tested elsewhere. A much smaller test of the AstraZeneca vaccine in South Africa raises questions about its effectiveness.

“If the virus could make one or two more mutations, it could escape further,” Ho warned.

Real red flag

“It’s time to cross the border,” said Dr. Paul Offit, a vaccine expert at the Children’s Hospital of Philadelphia, who advises the FDA when fully vaccinated people begin to be hospitalized with the mutant virus. It was.

It hasn’t happened yet, but “we have to get ready,” he added.

Moderna is looking for one option. Can a third dose of the original vaccine boost enough immunity to dodge some mutants, even if they are not in perfect agreement?

Ho of Colombia recommends testing if the overall antibody level is very high, as people may “still have enough cushion”.

Recipe adjustment

To be on the safe side, major manufacturers are also developing experimental mutant vaccines.

The COVID-19 vaccine produces antibodies that recognize the peplomer that covers the coronavirus. Mutations in the virus can alter peplomers in critical areas, making it difficult for vaccine-produced antibodies to recognize them.

Pfizer and Moderna vaccines are made with 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, simply change the payload. Exchanges the original genetic code for the mutated peplomer mRNA.

The AstraZeneca vaccine and Johnson & Johnson Shot will soon be deployed and are made with a cold virus designed to sneak the peplomer gene into the body. To tune the vaccine, the mutated gene must be used to propagate the cold virus. It’s a bit more complicated than the mRNA approach, but it’s not as tedious as rebuilding a traditional flu shot.

The Novavax vaccine, also in the final stage of testing, is made from laboratory-grown copies of peplomer proteins that can also be fine-tuned to match mutations.

Vaccine 2.0 test

The first-generation COVID-19 vaccine has been tested by tens of thousands of people and confirmed that they are functional and safe. This is a study that took months.

FDA vaccine director Dr. Peter Marks recently said the American Medical Association said that it is not necessary to repeat these studies in thousands of people simply by changing the recipe to better target viral mutations. Told to.

The FDA is still finalizing the requirements, but Marks said the FDA intends to be “quite agile.” If an updated vaccine is needed, tests in hundreds of people are likely to be sufficient to determine if it provokes a good immune response, he said.

But the bigger question: If there are only a few places facing vaccine-resistant viral variants, do authorities want a variant-only shot or vaccine that protects from two types in one jab? After all, the flu vaccine protects against three or four different types in a single shot.

John Grabenstein, a former Merck vaccine executive at the Vaccination Behavior Coalition, said companies first need to do some basic research to ensure that the mutant-only version properly restores the immune system. Said there is. Second, the combination shot requires further testing to ensure that both types have equivalent responses.

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