A search for solutions such as Omicron BA.4, BA.5 subvariants found to escape antibodies


According to new data from researchers at Beth Israel Deaconess Medical Center, Harvard Medical, the Omicron BA.4 and BA.5 subvariants appear to escape antibody responses both among people who have had a previous Covid-19 infection and among those that have been fully vaccinated and enhanced. School.

However, Covid-19 vaccination is still expected to provide substantial protection against serious disease, and vaccine manufacturers are working on upgraded shots that could elicit a stronger immune response against the variants.

Levels of neutralizing antibodies caused by a previous infection or vaccination are several times lower than 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.

“We observed 3-fold reductions in vaccination and infection-induced neutralizing antibody titers against BA4 and BA5 compared to BA1 and BA2, which are already substantially lower than the original COVID-19 variants,” Dr. Dan Barouch, author of the article and director of the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center in Boston, wrote in an email to CNN.

“Our data suggest that these new Omicron sub-variants will likely be able to lead to spikes in infections in populations with high levels of vaccine immunity and natural immunity to BA1 and BA2,” wrote Barouch. “However, vaccine immunity is likely to still provide substantial protection against severe disease with BA4 and BA5.”

The newly published findings echo separate research by Columbia University scientists.

They recently found that the BA.4 and BA.5 viruses were more likely to escape antibodies from the blood of fully vaccinated and augmented adults than other Omicron sub-variants, increasing the risk of breakthrough Covid-19 infections.

The authors of that separate study say their findings indicate an increased risk of reinfection, even in people who have previous immunity against the virus. The U.S. Centers for Disease Control and Prevention estimates that 94.7% of the U.S. population aged 16 and over have antibodies to the coronavirus that causes Covid-19 through vaccination, infection, or both.

BA.4 and BA.5 caused about 35 percent of new Covid-19 infections in the United States last week, up from 29 percent the week before, according to data shared by the U.S. Centers for Disease Control and Prevention Tuesday.

BA.4 and BA.5 are the fastest-spreading variants reported to date and are expected to dominate transmission of Covid-19 in the United States, the United Kingdom and the rest of Europe within the next few weeks, according to the Center. European Union for Disease Prevention and Control.

In the New England Journal of Medicine paper, among 27 research participants who had been vaccinated and boosted with the Pfizer / BioNTech coronavirus vaccine, the researchers found that two weeks after the booster dose, neutralizing antibody levels against Omicron’s sub-variants were much lower than the original coronavirus response.

Levels of neutralizing antibodies were a factor 6.4 lower than in BA.1; by a factor of 7 against BA.2; by a factor of 14.1 versus BA.2.12.1 and by a factor of 21 versus BA.4 or BA.5, the researchers described.

Among the 27 participants who had previously been infected with the BA.1 or BA.2 subvariants a median of 29 days earlier, the researchers found similar results.

In those with prior infection – most of whom had also been vaccinated – the researchers described neutralizing antibody levels lower by a factor of 6.4 against BA.1; by a factor of 5.8 against 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 what exactly neutralizing antibody levels mean for vaccine efficacy and whether similar findings would emerge among 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 leakage,” Barouch wrote in the email. “As pandemic restrictions are lifted, it is important to remain vigilant and continue to study new variants and sub-variants as they emerge.”

A separate study, published in the journal Nature last week, found that Omicron can evolve mutations to evade immunity elicited from a previous BA.1 infection, suggesting that BA.1-based vaccine boosters may not achieve a broad spectrum protection against new Omicron sub-variants such as BA.4 and BA.5.

As for what all of this means in the real world, Dr. Wesley Long, an experimental pathologist at Houston Methodist Hospital, told CNN that people should be aware they could get sick again, even if they’ve already had Covid-19.

“I think I’m a little worried about people who have recently had it, perhaps having a false sense of security with BA.4 and BA.5 on the rise, because we have seen some cases of reinfection and I have seen some cases of reinfection with people who have had a BA.2 variant in the past few months, ”he said.

Some vaccine manufacturers have developed variant-specific vaccines to improve antibody responses against coronavirus variants and sub-variants of concern.

“Reinfections will be pretty inevitable until we have vaccines or widespread mandates that prevent cases from reoccurring. But the good news is that we are, I believe, in a much better place than we were without the vaccines, “said Pavitra Roychoudhury, an acting teacher at the University of Washington’s Department of Laboratory Medicine and Pathology. , which was not involved in the paper of the New England Journal of Medicine.

“There is so much of this virus out there that it seems inevitable,” he said of the Covid-19 infections. “We hope the protections we have in place will lead to mostly mild infections.”

Moderna’s bivalent Covid-19 vaccine, dubbed mRNA-1273.214, elicited a “potent” immune response against Omicron BA.4 and BA.5 subvariants, the company said Wednesday.

This bivalent booster vaccine candidate contains components of both Moderna’s original Covid-19 vaccine and a vaccine that targets the Omicron variant. The company said it is working to complete regulatory requests in the coming weeks to require it to update the composition of its booster vaccine to be mRNA-1273.214.

“In the face of the continued evolution of SARS-CoV-2, we are very encouraged that mRNA-1273.214, our leading drop recall candidate, has shown high neutralizing titers against the BA.4 and BA.5 subvariants, which represent an emerging threat to global public health, “said Stéphane Bancel, CEO of Moderna, in Wednesday’s announcement. SARS-CoV-2 is the coronavirus that causes Covid-19.

“We will be sending this data to regulators urgently and are preparing to deliver our next generation bivalent booster starting in August, in anticipation of a potential increase in SARS-CoV-2 infections due to Omicron’s sub-variants at the start. autumn, “said Bancel.

The U.S. Food and Drug Administration’s Vaccines and Related Biological Products Advisory Committee will meet next week to discuss the composition of Covid-19 vaccines that could be used as boosters this fall.

The data that Moderna released on Wednesday, which has not been published in a peer-reviewed journal, showed that one month after administering a 50 microgram dose of the mRNA-1273.214 vaccine to people who had been vaccinated and boosted, the vaccine elicited “potent neutralizing antibody responses against BA.4 and BA.5, increasing levels 5.4-fold in all participants regardless of whether they had a previous Covid-19 infection and 6.3-fold in the subset of those unprecedented of infection. These neutralizing antibody levels were about 3 times lower than previously reported neutralizing levels against BA.1, Moderna said.

These results add to the data that Moderna previously released earlier this month, showing that the 50 microgram dose of the bivalent booster generated a stronger antibody response against Omicron than the original Moderna vaccine.

Moderna data suggest that “the bivalent booster may confer greater protection against omicron strains BA.4 and BA.5 than re-administration of the original vaccine to increase protection in the entire population. Although the information is based on antibody levels, the companies comment that similar levels of antibodies protected against clinical disease caused by other strains are the first suggestion of an emerging “immune correlate” of protection, although it is hoped that this ongoing study is also evaluating rates of clinical disease and antibody responses, “said Penny Ward, an independent pharmaceutical physician and visiting professor of pharmaceutical medicine at King’s College London, in a statement released Wednesday by the UK-based Science Media Center. involved in Moderna work.

“It has been previously reported that the bivalent vaccine is well tolerated with temporary ‘reactogenic’ effects similar to those following the univalent booster injection, so we can anticipate that this new mixed vaccine should be well tolerated,” Ward said in part. “As we head into the fall with omicron variants dominating the covid infection landscape, it certainly makes sense to consider using this new bivalent vaccine, if available.”


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