Does Any Monoclonal Antibody Work Against BA.2?

Sotrovimab, the only monoclonal antibody currently authorized to treat Omicron, appeared to lose its neutralizing activity against the Omicron subvariant, BA.2, lab data showed.

Neutralization activity for sotrovimab was 27-fold lower against BA.2 than against the original Omicron variant, BA.1, reported David Ho, MD, of Columbia University in New York City, and colleagues in a pre-print in bioRxiv.

BA.2 has blanketed COVID cases in Europe, and according to the latest CDC data, it comprises 3.6% of COVID cases in the U.S.; prior pre-print research found it to be more transmissible than the original Omicron.

Manufacturer Vir Biotechnology fired back against the study from Ho's group, saying its own lab data suggest sotrovimab sufficiently retains neutralizing activity against BA.2; the company plans to publish its own pre-print in bioRxiv shortly.

Importantly, Vir CEO George Scangos noted in the statement that the "500 mg dose of sotrovimab is sufficient to retain activity against the BA.2 variant." While this is the dose authorized by the FDA, Ho's group did not indicate the dosing in their pre-print.

They looked at neutralizing activity of the Omicron sublineages, first using convalescent sera. They found "a marked and significant loss of neutralizing activity" against both BA.2 and sublineage, BA.1+R346K, with "neutralizing titers dropping below the limit of detection."

They added that this drop in neutralizing activity was "less prominent" among sera from individuals who received a booster dose of vaccine, where the mean titer was "slightly lower" for BA.2, but the difference was non-significant compared to BA.1.

Ho's team then used 19 neutralizing monoclonal antibodies, where all but three had their emergency use authorization (EUA) altered by the FDA for being ineffective against Omicron.

Interestingly, while the group noted that all class 3 antibodies "lost greater neutralizing potency against BA.2 versus BA.1 sublineages," cilgavimab/tixagevimab (Evusheld) "retained activity against BA.2."

However, as they noted, this combination is only authorized for pre-exposure prophylaxis, not treatment.

"Presently, no authorized therapeutic monoclonal antibody could adequately treat all sublineages of the Omicron variant," they concluded.

Comment