The latest Omicron subvariants behind new COVID-19 surges in the United States and abroad have an enhanced ability to escape immunity conferred by three vaccine doses and all but one antibody therapy tested, finds a laboratory study published yesterday in Nature.Omicron BA.2.12.1, BA.4, and BA.5, the latter two of which now make up more than 70% of US COVID-19 infections, are highly transmissible and evasive owing to new mutations in the virus's spike proteins.A team led by Columbia University scientists studied the ability of SARS-CoV-2 antibodies to neutralize the subvariants.
The antibodies were obtained from the sera of participants who had either received at least three doses of an mRNA COVID-19 vaccine or who were infected with Omicron after receiving two doses.The spike protein of BA.2.12.1 has two more mutations than BA.2, while BA.4 and BA.5 have identical spike proteins with four additional alterations. "This antigenic distance is similar to that between the Delta variant and the ancestral virus and thus is likely to lead to more breakthrough infections in the coming months," the authors wrote.BA.4/5 at least 4-fold more resistantRelative to BA.2, the BA.2.12.1 subvariant was about 80% more resistant (1.8-fold) after three vaccine doses, but BA.4 and BA.5 were at least 4.2 times more resistant, increasing the likelihood of breakthrough infections.When the researchers also evaluated the ability of 19 monoclonal antibody therapies to neutralize the subvariants, they found that only one—Eli Lilly's intravenous bebtelovimab—retained its full efficacy against these strains.Bebtelovimab is authorized for the treatment of high-risk adults and children 12 years and older diagnosed as having mild-to-moderate illness.