Previous vaccines may not have enough antibodies? There is a growing trend of new omicron subvariants evading antibodies

New research shows that the three omicron subvariants of SARS-CoV-2 currently circulating — including two that currently account for nearly 50 percent of reported COVID-19 infections in the U.
S.
— are better at avoiding vaccines and neutralizing antibodies
produced by infections than earlier versions of omicron.

The scientists tested serum samples of vaccinated, previously infected or recently infected healthcare workers for neutralizing antibodies to combat several circulating subvariants
.
Three subvariants were significantly resistant to antibody immune responses: BQ.
1, BQ.
1.
1, and BA.
2.
75.
2
.

According to the Centers for Disease Control and Prevention (CDC), BQ.
1 and BQ.
1.
1 are subvariants of the BA.
4/5 omicron variant that has dominated the United States in the past few months and each now account for about a quarter
of current infections.
BA.
2.
75.
2, a mutant of the BA.
2 mutant, is the best of all variants that dodged neutralizing antibody testing, but currently accounts for only a very small percentage of
reported diseases in the United States.

"Overall, subvariants BQ.
1 and BQ.
1.
1 are much better than previous variants in terms of evasion promoter-mediated antibody responses—neutralizing antibody titers are clearly much
lower.
These two variants are becoming dominant," said Shan-Lu Liu, senior author of the study and professor of virology in The Ohio State's Department of Veterinary Biological Sciences
.

"It's important to be aware when traveling and partying on holidays that the SARS-CoV-2 variant continues to evolve, and if you had received the first booster more than six months ago, you might consider getting the second booster because the antibodies produced by a single booster may now be too low to be protective
.
"

The study was published in the journal Cell Host and Microbes
.

While the third booster is a newer bivalent formulation that is currently being given to eligible people, more than 48 percent of eligible people have not received a booster dose
, according to the Centers for Disease Control and Prevention.
Liu's lab has previously shown that the COVID-19 booster vaccine provides strong and broad antibody protection against a range of micron gene variants, while the second booster restores the decreasing antibody count to protective levels
.

In the current study, serum samples were received from healthcare workers who received two doses of the mRNA vaccine and one booster dose, or who were infected in early or late omicron waves
.

The results showed that vaccines and individual boosters produced about 20-fold
fewer antibodies that neutralized BQ.
1 and BQ.
1.
1 compared to neutralizing antibodies against the original or parental SARS-CoV-2 virus.
Similarly, neutralizing antibody levels or titers produced during BA.
1 micron wave infection were significantly lower for the BQ subvariant than for parental viruses, while antibody titers for the BQ subvariant produced during BA.
4/5 wave infection did not reach detectable levels
.

"Our findings suggest that you cannot count on natural infection to prevent the currently circulating Omegaly subvariant
," said Liu, associate director of the Ohio State University Retrovirus Research Center and co-director of the Viruses and Emerging Pathogens Program at The Ohio State University's Institute of Infectious Diseases.

Liu and colleagues conducted cell culture studies using pseudovirus, a non-infectious viral core whose surface is surrounded by different SARS-CoV-2 spike proteins and structurally matched
to known variants.
The methods used to detect neutralizing antibodies in blood samples account for the different levels of antibodies
produced by individuals.

In the study, collaborator and co-author Kai Xu at The Ohio State University created a structural model of individual amino acids altered by the latest mutation on the spike protein, identifying key molecules in which some subvariants rearrange so they can prevent antibodies from binding
to viral particles 。 The model showed that one of the amino acids, called N460K, also allows BQ.
1 and BQ.
1.
1 particles to enter host cells more efficiently and force host cells to fuse together, a step in viral infection that can increase pathogenesis — which contributes to the onset of the disease, the development of more severe symptoms, and the ability of the disease to
spread.

"From my perspective, this is noteworthy because the original omicron variant is not very pathogenic – it doesn't cause much cell fusion at all, but we're now seeing a trend of new subvariants with increased cell fusion that puts the virus in a better position to cause infection and morbidity
.
"

Studies produced by other labs on neutralizing antibodies to bivalent enhancers suggest that newer boosters will provide protection
against new small particle subvariants, Liu said.

But Liu has submitted a paper on another subvariant called XBB, a recombinant variant produced by the exchange of genetic material between two BA.
2 small microparticle subvariants, showing what he called "extraordinary" resistance to neutralizing antibodies produced by vaccinations and previous infections
.

"This virus can do unexpected things," he said
.
"We still need to do a good job of monitoring and keep a close eye on these emerging concerns
.
"

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