Omicron subvariants BA.4 and BA.5 appear to escape antibody responses in both people who have had a previous Covid-19 infection and those who have been fully vaccinated and boosted, according to new data from researchers at Beth Israel Deaconess Medical Center, from Harvard Medical School.
However, Covid-19 vaccination is still expected to provide substantial protection against serious illness, and vaccine makers are working on updated shots that could elicit a stronger immune response against the variants.
The levels of neutralizing antibodies that trigger a previous infection or vaccinations are several times lower against the BA.4 and BA.5 subvariants compared to the original coronavirus, according to new research published Wednesday in the New England Journal of Medicine. published.
“We observed 3-fold reductions in neutralizing antibody titers induced by vaccination and infection against BA4 and BA5 compared to BA1 and BA2, which are already significantly lower than the original COVID-19 variants,” Dr. Dan Barouch, an article author and director of the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center in Boston, in an email to CNN.
“Our data suggest that these new Omicron subvariants are likely to lead to increases in infections in populations with high vaccine immunity and natural BA1 and BA2 immunity,” Barouch wrote. “However, it is likely that vaccine immunity will still provide substantial protection against serious diseases involving BA4 and BA5.”
The newly published findings reflect separate research by scientists at Columbia University.
They recently found that the BA.4 and BA.5 viruses were more likely to escape antibodies from the blood of fully vaccinated and boosted adults compared to other Omicron subvariants, reducing the risk of vaccine breakthrough Covid- 19 infections increased.
The authors of that separate study say their results indicate a higher risk of reinfection, even in people who already have some immunity to the virus. The U.S. Centers for Disease Control and Prevention estimate that 94.7% of the U.S. population aged 16 and older has antibodies to the coronavirus that causes Covid-19 through vaccination, infection, or both.
BA.4 and BA.5 caused an estimated 35% of new Covid-19 infections in the United States last week, up from 29% the week before, according to data released Tuesday by the US Centers for Disease Control and Prevention. shared.
BA.4 and BA.5 are the most rapidly spreading variants reported to date, and according to the European Center for Disease Prevention and Control.
‘COVID-19 still has the ability to mutate further’
In the New England Journal of Medicine paper, the researchers found that among 27 study participants who had been vaccinated and boosted with the Pfizer/BioNTech coronavirus vaccine, two weeks after the booster dose, the levels of neutralizing antibodies to Omicron subvariants were much lower than the response to the original coronavirus.
Neutralizing antibody levels were 6.4-fold lower relative to BA.1; by a factor of 7 compared to BA.2; by a factor of 14.1 against BA.2.12.1 and by a factor of 21 against BA.4 or BA.5, the researchers described.
In 27 participants who had previously been infected with the BA.1 or BA.2 subvariants on average 29 days earlier, the researchers found similar results.
In those with a previous infection — most of whom had also been vaccinated — the researchers described neutralizing antibody levels that were 6.4-fold lower against BA.1; by a factor of 5.8 relative to BA.2; by a factor of 9.6 against BA.2.12.1 and by a factor of 18.7 against BA.4 or BA.5.
More research is needed to determine exactly what neutralizing antibody levels mean for vaccine effectiveness and whether similar findings would emerge in a larger group of participants.
“Our data suggests that COVID-19 still has the ability to mutate further, resulting in increased transmissibility and increased antibody escape,” Barouch wrote in the email. “As pandemic restrictions are lifted, it is important that we remain vigilant and continue to study new variants and subvariants as they arise.”
A separate study, published last week in the journal Nature, found that Omicron can develop mutations to evade the immunity elicited by a previous BA.1 infection, suggesting that vaccine boosters based on BA.1 may not achieve broad-spectrum protection against new Omicron sub-variants such as BA.4 and BA.5.
What all this means in the real world, Dr. Wesley Long, an experimental pathologist at Houston Methodist Hospital, told CNN that people should be aware that they can get sick again, even if they’ve had Covid-19 before.
“I think I’m a little concerned about people who have had it, maybe have a false sense of security recently with BA.4 and BA.5 on the rise because we’ve seen some cases of reinfection and I’ve seen some …cases of reinfection with people who had a BA.2 variant in recent months,” he said.
Some vaccine manufacturers have developed variant-specific vaccines to enhance antibody response against coronavirus variants and sub-variants of concern.
“Re-infections will be pretty inevitable until we have vaccines or widespread mandates that will prevent the numbers from increasing again. But the good news is we’re in a much better place than without the vaccines,” said Pavitra Roychoudhury, an acting instructor. the Department of Laboratory Medicine and Pathology at the University of Washington, which was not involved in the New England Journal of Medicine paper.
“There is so much of this virus that it seems inevitable,” she said of Covid-19 infections. “Hopefully the protections we have will lead to a mostly mild infection.”
Efforts underway to update Covid-19 vaccines
Moderna’s bivalent Covid-19 vaccine booster, called mRNA-1273,214, elicited a “potent” immune response against the Omicron subvariants BA.4 and BA.5, the company said Wednesday.
This bivalent booster vaccine candidate contains components from both Moderna’s original Covid-19 vaccine and a vaccine targeting the Omicron variant. The company said it is working to finalize its regulatory filings in the coming weeks with a request to update its booster vaccine composition to mRNA-1273,214.
“In light of the continued evolution of SARS-CoV-2, we are very encouraged that mRNA-1273,214, our fall lead booster candidate, has shown high neutralizing titers against the BA.4 and BA.5 subvariants , which is an emerging threat to global public health,” said Stéphane Bancel, Moderna’s chief executive officer, in Wednesday’s announcement. SARS-CoV-2 is the coronavirus that causes Covid-19.
“We will urgently submit this data to regulators and are preparing to deliver our next-generation bivalent booster from August, pending a potential rise in SARS-CoV-2 infections due to Omicron subvariants in early fall” Bancel said.
The U.S. Food and Drug Administration’s Advisory Committee on Vaccines and Related Biologics will meet next week to discuss the makeup of Covid-19 vaccines that could be used as boosters this fall.
Data released by Moderna on Wednesday, which has not been published in a peer-reviewed journal, showed that one month after a 50 microgram dose of the mRNA-1273,214 vaccine was administered to people who had been vaccinated and boosted, the vaccine elicited “potent” neutralizing antibody responses to BA.4 and BA.5, increasing levels 5.4-fold in all participants regardless of prior Covid-19 infection and 6.3-fold in the subgroup of those with no history of previous infection. These levels of neutralizing antibodies were about 3 times lower than previously reported neutralizing levels against BA.1, Moderna said.
These findings add to data released by Moderna earlier this month showing that the 50 microgram dose of the bivalent booster elicited a stronger antibody response against Omicron than the original Moderna vaccine.
Moderna’s data suggest that “the bivalent booster could provide greater protection against the BA.4 and BA.5 omicron strains than re-administration of the parent vaccine to better protect the population. Although the information is based on antibody levels, The companies on that similar levels of antibody protected against clinical disease caused by other strains is the first suggestion of an emerging ‘immune correlate’ of protection, although it is hoped that this ongoing study also assesses the number of clinical diseases and antibody responses,” Penny Ward, a independent pharmaceutical doctor and visiting professor of pharmaceutical medicine at King’s College London, in a statement released Wednesday by the UK-based Science Media Center. She was not involved in Moderna’s work.
“The bivalent vaccine has been previously reported to be well tolerated with transient ‘reactogenic’ effects similar to those after the univalent booster injection, so we can expect this new mixed vaccine to be well tolerated,” Ward said in part. “As we head into the fall with ommicron variants dominating the covid infection landscape, it certainly makes sense to consider using this new bivalent vaccine if available.”
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