The omicron subvariant BA.4.6, now increasing in prevalence in the U.S., appears to evade the neutralizing antibodies induced by currently available vaccines or prior COVID-19, according to an NEJM letter. An in vitro test of commonly used drugs and monoclonal antibodies concludes that remdesivir, molnupiravir, and nirmatrelvir and the monoclonal antibodies bebtelovimab and imdevimab retain effectiveness against BA.4.6, authors of a second letter report.
“Our data show that the BA.4.6 omicron subvariant markedly escaped neutralizing antibodies induced by infection or vaccination, with values that were lower than BA.5 titers by a factor of 2 to 2.7, which suggests continued evolution of SARS-CoV-2,” the first set of authors write. “These findings provide immunologic context for the increasing prevalence of BA.4.6 in populations in which BA.5 is currently dominant. Moreover, the R346T mutation had also recently been observed in other omicron subvariants, including BA.2.75 and BA.5, which suggests the biologic relevance of this mutation. The potential effect of the emergence of the BA.4.6 subvariant on vaccine boosters containing BA.5 immunogens or on infection with BA.5 remains to be determined.”
In the second letter, the researchers found that two BA.4.6 isolates had susceptibility to some antiviral products similar to the sensitivity of the original SARS-CoV-2 wild type virus, with the 50% inhibitory concentration higher by a factor of 1.6 with remdesivir, 5.7 with mulnupiravir, and 4.1 with nirmatrelvir. Bebtelovimab and imdevimab retained effectiveness, but the “monoclonal antibodies casirivimab, sotrovimab, tixagevimab, and cilgavimab may not be effective against BA.4.6,” the letter states.