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Penn Medicine Researcher explains how Covid Vaccines will work against the new variants.

How Will COVID-19 Vaccines Work Against New Variants?

New research shows that SARS-CoV2 — the virus that causes COVID-19 — could evolve to not only be more transmissible but also more lethal. But mRNA vaccines, like those developed by Moderna and Pfizer–BioNTech, can be readily updated.


According to Drew Weissman, MD, PhD, a professor of Infectious Diseases who pioneered the development of mRNA vaccine technology, it’s pretty simple from a scientific perspective. He said, “You only need the sequence, and we have the sequence of all the variants.”


In December 2020, as quickly as excitement grew over the new COVID-19 vaccines that had been approved for use, worry took over. Evidence worldwide suggested that SARS-CoV-2, the virus that causes COVID-19, was mutating. P.1, a variant first discovered in Brazil, ravaged the Amazonian city of Manaus. B.1.1.7, first identified in the United Kingdom, was thought to transmit more readily and, within a matter of weeks, led to a surge in cases and became the dominant strain in Britain, And B.1.351, found in South Africa, was also causing worry, especially because researchers recently found it may evade some of the newest vaccines.


Viruses mutate all the time and usually mutate to become more transmissible. New research shows that SARS-CoV2 — the virus that causes COVID-19 — could evolve to not only be more transmissible but also more lethal. Over the last year, the virus has already shape-shifted multiple times, which raises the possibility that COVID-19 vaccines may have to be updated frequently, similar to how flu vaccines change every year to account for the new circulating strains.


This may all sound like bad news, but these vaccines can actually be readily updated, especially the ones developed by Moderna and Pfizer–BioNTech, which are based on mRNA technology.


As scientists studied the potential use of mRNA vaccines over the last decade, they hoped that this cutting-edge technology could be used rapidly in emerging pandemics, says Deborah Fuller, a microbiologist at the University of Washington who is working on developing a COVID-19 vaccine.


mRNA vaccines train our bodies to develop an immune response to a segment of a pathogen. For the COVID-19 vaccines, the mRNA segment codes for a portion of the spike protein, a region of SARS-CoV2 that helps the virus enter our cells. After getting vaccinated, our body turns the message into a protein so our immune system mounts an immune response to the protein — similar to what would happen if we were exposed to the full virus.


The message portion of these vaccines can be tweaked as the virus mutates. Scientists can take the mRNA sequence of the new strains and swap it in to produce new vaccines.


In other words, it’s pretty simple from a scientific perspective to update these vaccines. “You only need the sequence, and we have the sequence of all the variants,” says Drew Weissman, an immunologist at the University of Pennsylvania who pioneered the development of mRNA vaccines.


Already, Pfizer and Moderna are working to update the original vaccines to account for the variants. Pfizer is hoping that it can happen in as fast as 60 days.


COVID-19 vaccines not based on mRNA but DNA can also be updated by swapping out the genetic material for the sequence of the updated variants. The issue here is that the DNA-based vaccines are surrounded by another virus, called the adenovirus, which helps the vaccine get inside cells to elicit an immune response. Researchers are concerned about multiple shots of these adenovirus vaccines.


“If you repeatedly immunize people with these … vaccines, you’re going to start to build up immunity against the carrier vector itself,” says Fuller. “To me, a lot of the adenovirus-based vaccines are a one-and-done shot. These particular vaccines will have diminishing returns and not work as well,” she says. It’s possible, however, Fuller says, to combine different vaccines. For instance, someone can at first get an adenovirus vaccine and then, as the virus mutates, get booster vaccines made from mRNA.


The rapid timeframe in manufacturing these vaccines is only a small part of getting them mass-distributed. Updating vaccines won’t be the challenging part, scientists say. Vaccine developers hope that the Food and Drug Administration, which oversees the approval of vaccines, will come up with a regulatory framework to expedite the process for updated COVID vaccines to get into the arms of people.


Flu vaccines can be updated regularly without undergoing clinical trials because the only thing that changes year to year are the strains being targeted — all other parts of the formulation remain the same.


On February 1, Peter Marks, the director of the Center for Biologics Evaluation and Research at the FDA, said that the agency is looking to develop a “pretty streamlined process.” The initial studies to update these vaccines will require clinical trials of a few hundred people — rather than thousands of people in the trials for the original vaccines — and look at an immune response, rather than follow the patients for a longer period of time to determine if the vaccines are efficacious.


Some researchers believe that in the future, we could have a single shot with multiple mRNAs that targets multiple variants. Weissman and his colleagues have shown that it’s possible to put up to 20 different mRNAs into a vaccine and still get a good immune response to all 20 targets.


Adding more targets to a COVID-19 vaccine could also mean more clinical trials and a longer approval process. That’s what happened when flu vaccine researchers went from incorporating three different strains of flu to four in a single shot. “We had to conduct additional clinical trials to show that adding a different strain didn’t interfere with the responses,” says Kawsar Talaat, an expert on vaccine trials at the Johns Hopkins Bloomberg School of Public Health.


COVID-19, like all other viruses, will continue to mutate. The good news is that the vaccines can be rapidly updated, as mRNA vaccines might lead the fight in not only COVID but other infectious diseases. We still need to wait to see how the FDA will regulate them so they can be used even as COVID-19 continues to be a part of our everyday lives.


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