Thursday , March 4 2021

Existing vaccines should work against new variants of the coronavirus – for now



For more than a year, the COVID-19 pandemic has been a new threat to health authorities: new variants of the SARS-CoV-2 virus. Recently, researchers around the world have identified three notable options: B.1.1.7, first found in the UK in December; 501Y.V2, found in South Africa in December; and P1, detected in Brazil on 13 January.

There is no evidence that any of these options are more deadly than the virus versions that appeared earlier. However, some may be more transmissible due to mutations that alter the coronavirus protein, the part of the virus that attaches to human cells and the part that the vaccine targets. If left unchecked, these options can spread faster and cause even more death and suffering.

However, as vaccines spread around the world, researchers see early signs that existing vaccines need to work with the body’s multifaceted immune system to provide a certain level of protection against mutated versions of the virus.

“The options really have changed in [virus’s] protein, but not enough to make the vaccine unprotected, ”said Arnold Montt, acting chairman of the U.S. Administration’s Advisory Committee on Vaccines and Related Organic Products. a Jan. 11 interview with a medical journal JAMA. “It simply came to our notice then [existing vaccines] should work and we’ll find out more in the next couple of weeks. ”

To slow the evolution of the virus into new variants, experts say it is very important to do what we know to prevent the spread of the virus – wear masks, wash your hands, keep a social distance and get vaccinated as soon as possible.

“We haven’t seen any evidence yet that the new options won’t be covered by the vaccine, and in fact the way to stop the new options is to contain the virus,” says Philip Dormitser, chief researcher on viral vaccines. in Pfizer’s vaccine research division. “The fewer virus replications in the world, the fewer options will be created.”

If a vaccine-resistant version of SARS-CoV-2 appeared, the current vaccines could be modified to eliminate new mutations, Dormitzer adds.

Diverse immune response to COVID-19

Our body produces a wide range of antibodies in response to a given vaccine or natural infection. In the case of COVID-19, these antibodies target multiple parts of the SARS-CoV-2 protein, rather than just one region that may change in a mutated variant of the virus. Basically, this variety of antibodies complicates a viral mutation to make the vaccine ineffective.

“If there is a mutation that destroys one of the antibody-binding sites, in this scenario it will reduce the binding activity of that specific antibody, but there are many, many other antibodies that are not associated with that site,” says Pei-Yong Shi, a virologist. and a microbiologist at the Medical Department of the University of Texas at Galveston.

In addition to antibodies, vaccines also activate T cells – immune cells that play an important role in the body’s early response to SARS-CoV-2, says Dormitser. Vaccine test data show that these immune cells can begin to protect the body before producing large amounts of antibodies.

For example, in three Pfizer trials, for example, patients who received the first of two doses of the vaccine began to show signs of protection after 10-14 days, although trials in the first phase of the vaccine showed that many patients did not necessarily have high antibody levels. in their blood at the time.

“Either only a small amount of neutralizing antibodies are needed to protect against this virus, or something else protects but not [a] neutralizes antibodies, ”says Dormitser, referring to the possible role of T cells in stopping the virus.

In light of our complex immune response to SARS-CoV-2, Dormiter says that even if antibodies caused by the vaccine do not bind so well to current and future options, it is possible that these vaccines may provide protection.

Such partial protection is already seen in seasonal flu vaccines, says Helen Chu, an immunologist at the University of Washington in Seattle. “Even if you’re infected with a strain that doesn’t quite match what’s in the vaccine, you’re still protected,” she says. “And these [COVID-19] vaccines are much, much better than flu vaccines; The 95 percent efficiency is much better than the 50-60 percent we see with the flu. ”

Chu, who studies patients ’immune responses to respiratory viruses, has been following COVID-19 from the beginning. Last February, she helped take blood from the first U.S.-confirmed patient with COVID-19. Nothing about the emergence of options does not surprise her – or reduces confidence in the broad effectiveness of current vaccines.

“I have a vaccine and I know that every scientist and doctor I work with gets a vaccine,” she says. “I definitely wouldn’t pause based on the fact that there are new options.”

Watch for mutations

For several months, the researchers screened mutated versions of SARS-CoV-2 in the lab to see which mutations posed the greatest risk of increased virus transmission or the ability to evade the immune system.

Research focuses on the key mutations of the three major new variants. Each contains its own set of mutations, but some mutations occur independently in all three variants – meaning that it is these mutations that help the virus spread.

One of the mutations is N501Y, which alters an amino acid in the binding domain of the SARS-CoV-2 protein receptor, which is part of a protein that is directly fixed to the outer parts of human cells. Past studies have shown that this mutation may allow the virus to bind more efficiently to ACE receptors on human cells, making it more transmissible to humans and other animals. A study was published in September Science found that the mutation made SARS-CoV-2 more infectious in laboratory mice.

But this mutation alone does not seem to make the virus resistant to current vaccines. Shi’s lab in partnership with Pfizer researchers, including Dormitzer, used a genetic method to make two laboratory versions of SARS-CoV-2 that were identical except for the presence or absence of the N501Y mutation.

In a preliminary study published Jan. 7 on the bioRxiv server, Shi and Dormitzer’s team looked at how antibodies from 20 participants in the Pfizer-BioNTech vaccine responded to two types of the virus. Antibodies bind to the N501Y virus variant as well as to the mutation. “We’re very excited to see that the results don’t compromise the vaccine,” Shea says.

Despite this, Shea easily recognizes one of the key limitations of the study: new variants do not have only single mutations. For example, variant B.1.1.7 has eight different mutations that affect its spike protein. Over the next two to three weeks, Shi says, his lab will screen different combinations of mutations for further testing of the Pfizer-BioNTech vaccine.

Option 501Y.V2 has another mutation of concern: E484K, which also affects the receptor domain of the ligament protein. In a January 4 preprint published on bioRxiv, researchers from the Fred Hutchinson Cancer Research Center in Seattle found that this mutation plays a big role in how well antibodies bind to the virus protein.

When laboratory models of viruses with E484K and similar mutations were screened for antibodies in recovered patients with COVID-19, the antibodies of some patients were markedly less effective in binding to viruses with the mutation. However, it is important that currently permitted vaccines generate strong immune responses, and there is currently no evidence that variants with the E484K mutation will completely resist the immunity induced by the vaccine.

У a series of messages on Twitter, Jesse Bloom, senior author of the preprint, made it clear that reduced protection is worlds other than zero protection. “Should we worry about E484K and other mutations? Yes! That’s why so many of us work hard to study them. But we need to keep the perspective, ”he wrote. “Reduced neutralization does not mean a lack of immunity, and careful research will be needed to determine the implications for human protection.”

What if the vaccine needs to be modified?

Vaccine manufacturers are creating a framework for a rapid response if a future variant of SARS-CoV-2 does not respond to existing vaccines. Dormitzer, a Pfizer researcher, says any changes to vaccines should follow strong clinical observations that the new variant is spreading among people already immunized against COVID-19.

One of the benefits of the Pfizer-BioNTech and Moderna vaccines is that they can be upgraded quickly. But Dormitzer warns that laboratory research and production are just two steps in the long journey of a vaccine to someone’s hand. If the vaccine is upgraded, government regulators will need to test whether it is safe and effective. Researchers argue that policies that regulate regular updates of the seasonal flu vaccine could be a good foundation.

“Everyone wants to take the flu as a model, and I absolutely agree that the flu is our model,” says Dormitser. But “we need to figure out how we adapt the regulatory pathways – the empirical rules – used in influenza for this new virus.”

Importantly, researchers need to know when new options appear. All three are experts National Geographic respondents urged governments around the world to significantly increase the genomic sequence of SARS-CoV-2 and share the findings.

“We really need to keep a very close eye on the sequence of viruses in patients,” Shea says. “It’s the eyes and ears of our public health.”




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