Covid: Omicron subvariants BA.4 and BA.5 escape antibodies from vaccination and previous infection, studies suggest

Written by Javed Iqbal

However, Covid-19 vaccination is still expected to provide significant protection against serious illness, and vaccine manufacturers are working on updated shots that may elicit a stronger immune response to the variants.

“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 author of the paper 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 subvariants are likely to be able to lead to increases in infections in populations with high levels of vaccine immunity as well as natural BA1 and BA2 immunity,” Barouch wrote. “However, it is likely that vaccine immunity will still provide significant protection against serious illness with BA4 and BA5.”

The recently published results reflect separate research conducted by researchers at Columbia University.

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

The authors of the separate study say their findings point to a higher risk of re-infection, even in people who have some previous immunity to the virus. The U.S. Center for Disease Control and Prevention estimates 94.7% of the US population 16 years and older have coronavirus antibodies that cause Covid-19 through vaccination, infection, or both.
BA.4 and BA.5 caused an estimated 35% of new Covid-19 infections in the US last week, up from 29% the week before, according to data shared by the US Centers for Disease Control and Prevention on Tuesday.

BA.4 and BA.5 are the fastest-growing variants reported to date, and they are expected to dominate the Covid-19 transfer in the US, UK and the rest of Europe within the next few weeks, according to the European Center for Disease prevention and control.

‘COVID-19 still has the capacity to mutate further’

In the New England Journal of Medicine, researchers found among 27 researchers who had been vaccinated and boosted with the Pfizer / BioNTech coronavirus vaccine that two weeks after the booster dose, levels of neutralizing antibodies to Omicron subvariants were much lower than responses to the original coronavirus.

The neutralizing antibody levels were lower by a factor of 6.4 against BA.1; by a factor of 7 against BA.2; with a factor of 14.1 against BA.2.12.1 and with a factor of 21 against BA.4 or BA.5, the researchers described.

Among 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 previous infection – most of whom had also been vaccinated – the researchers described neutralizing antibody levels that were 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 exactly what the neutralizing antibody levels mean for the effectiveness of the vaccine and whether similar results would emerge among a larger group of participants.

“Our data suggest that COVID-19 still has the capacity to mutate further, resulting in increased transmissibility and increased antibody release,” Barouch wrote in the email. “When pandemic restrictions are lifted, it is important that we remain vigilant and continue to study new variants and sub-variants as they emerge.”

A separate study, published in the journal Nature found last week that Omicron may develop mutations to avoid immunity induced by a previous BA.1 infection, suggesting that vaccine boosters based on BA.1 may not achieve broad-spectrum protection against new Omicron subvariants such as BA.4 and BA. .5.
How well does our immunity to Covid-19 last?

As for 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 could get sick again, even though they have had Covid-19 before.

“I think I’m a little worried that people who’ve had it lately may have a false sense of security with BA.4 and BA.5 on the rise because we’ve seen some cases of re-infection and I have seen some cases of re-infection with individuals who had a BA.2 variant in the last few months, “he said.

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

“Re-infections will be pretty inevitable until we have vaccines or widespread mandates that will prevent cases from rising again. But the good news is that we, I think, are in a much better place than we were without the vaccines,” he said. Pavitra Roychoudhury, an acting instructor at the University of Washington’s Department of Laboratory Medicine and Pathology who was not involved in the New England Journal of Medicine paper.

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

Work is underway to update Covid-19 vaccines

Modern bivalent Covid-19 vaccine booster, called mRNA-1273.214, elicited a “potent” immune response against Omicron subvariants BA.4 and BA.5, the said Wednesday.
The hunt for long-term Covid-19 vaccines

This bivalent booster vaccine candidate contains components of both Modern’s original Covid-19 vaccine and a vaccine targeted at the Omicron variant. The company said it is working to complete regulatory submissions in the coming weeks with a request to update the composition of its booster vaccine to be mRNA-1273,214.

“In view of the continued development of SARS-CoV-2, we are very encouraged that mRNA-1273.214, our leading booster candidate for the autumn, has shown high neutralizing titers against the BA.4 and BA.5 subvariants, which represent an emerging threat. against 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 submit this data to regulators immediately and prepare to deliver our next generation of bivalent booster starting in August, ahead of a potential increase in SARS-CoV-2 infections due to Omicron subvariants in early autumn , “said Bancel.

The U.S. Food and Drug Administration’s advisory committee on vaccines and related biological products is meeting next week to discuss the composition of Covid-19 vaccines that can be used as boosters for the fall.
Moderna says updated Covid-19 vaccine booster shows stronger antibody response to Omicron

The data, which Moderna released on Wednesday and 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 individuals who had been vaccinated and boosted, the vaccine elicited “potent” neutralizing antibody responses to BA.4 and BA.5, boosting levels 5.4-fold in all participants, regardless of whether they had a previous Covid-19 infection and 6.3-fold in the subgroup of those without previous infection. These levels of neutralizing antibodies were about 3 times lower than previously reported neutralizing levels against BA.1, Moderna said.

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

Modern data suggest that “the bivalent booster may provide greater protection against BA.4 and BA.5 omicron strains than reintroducing the original vaccine to increase cross-population protection. Although the information is based on antibody levels, the companies comment, that similar levels of antibody protected against clinical disease caused by other strains are the first suggestion of a new ‘immune correlate’ of protection, although it is hoped that this ongoing study also assesses the frequency of clinical disease as well as antibody reactions, “Penny Ward, an independent pharmaceutical doctor and visiting professor of pharmaceutical medicine at King’s College London, said in a statement released by the British Science Media Center on Wednesday. She was not involved in Moderna’s work.

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

CNN’s Brenda Goodman contributed to this report.

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Javed Iqbal

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