Omicron subvariants BQ.1.1 and XBB.1 were more effective at escaping neutralizing antibodies compared with the BA.5 variant following both monovalent and bivalent mRNA boosters, new data suggested.

In 15 participants who had received a monovalent mRNA booster in 2022, neutralizing antibody titers against BA.5 were seven times higher than those for BQ.1.1, and 17 times higher than those for XBB.1, reported Dan Barouch, MD, PhD, of Beth Israel Deaconess Medical Center in Boston, and colleagues.

In 18 participants who had received a bivalent mRNA booster, neutralizing antibody titers against BA.5 were seven times higher versus those for BQ.1.1, and 21 times higher versus those for XBB.1, they noted in a correspondence published in the New England Journal of Medicine (NEJM).

Median antibody titers to BA.5 were 2,829 and 3,693 with the monovalent and bivalent boosters, respectively, and 170 and 175 to the XBB.1 strain.

Barouch and team also looked at neutralizing antibody titers from 16 participants who received a monovalent vaccine in 2021, with neutralizing antibody titers three times higher for BA.5 versus BQ.1.1 and eight times higher versus XBB.1.

“These findings suggest that the BQ.1.1 and XBB.1 variants may reduce the efficacy of current mRNA vaccines and that vaccine protection against severe disease with these variants may depend on CD8 T-cell responses,” they wrote.

The researchers noted that participants’ background immunity likely played a part in the 2022 monovalent booster results.

“The higher neutralizing antibody titers against Omicron variants after monovalent mRNA boosting in the 2022 cohort than in the 2021 cohort probably reflect the greater numbers of vaccine doses and infections in the 2022 cohort,” they wrote.

Omicron variants, including the BA.4 sublineage BA.4.6, the BA.5 sublineages BF.7 and BQ.1.1, the BA.2 sublineage BA.2.75.2, and the BA.2 lineage recombinant XBB.1 have the R346T mutation in the spike protein. However, despite this similarity, the difference in the variants’ ability to evade neutralizing antibodies induced by vaccination and infection has been unclear.

“The incorporation of the R346T mutation into multiple new SARS-CoV-2 variants suggests convergent evolution,” Barouch and team wrote.

For this study, the researchers assessed neutralizing antibody titers from 16 participants who had received the monovalent Pfizer-BioNTech mRNA booster in 2021. Those with a history of infection were excluded from this group.

They also evaluated neutralizing antibody titers from 15 participants who had received a monovalent mRNA booster in 2022 and 18 participants who had received a bivalent mRNA booster in 2022, most of whom had received three previous doses of vaccine. Of these groups, 33% had a documented SARS-CoV-2 Omicron infection, but the researchers suspected that a majority may have in fact been previously infected.

Among the 2021, 2022 monovalent, and 2022 bivalent groups, median ages were 34, 50, and 42, respectively, and 94%, 87%, and 61% were women. Ethnicity was reported as non-Hispanic in 88%, 93%, and 94% of participants, respectively. The groups were 20 days, 32 days, and 21 days from their last vaccine, respectively.

In a recent audio interview published on the NEJM‘s website, NEJM Editor-in-Chief Eric J. Rubin, MD, PhD, Lindsey R. Baden, MD, and Stephen Morrissey, PhD, all of Brigham and Women’s Hospital in Boston, discussed the evolution of the new variants.

“The bad news is that these variants are relatively poorly neutralized by serum derived from people who’ve been vaccinated and/or previously infected,” Rubin said. “On a somewhat more positive note, while there certainly has been an increase in COVID-related hospital admissions recently, this seems to be driven largely by the increase in the number of total cases in the community rather than worsened disease caused by XBB and these other variants; however, this is really still anecdotal rather than systematic data.”

Lindsey agreed, adding, “I do suspect that it’s not going to be random and evenly distributed across communities with different variants, but always new variants will emerge, and those which have advantages will then dominate and spread widely, which I think XBB is doing as an example of some degree of immune evasion, allowing it to be successful in communities with high levels of hybrid immunity.”

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