Eight out of 10 antibody therapy available for treatment of Covid-19 patients do not inhibit the new and emerging sub-variants of Omicron such as BA.2.12.1, BA.4, and BA.5, according to a study published in The Lancet Infectious Diseases. 

A team of researchers, including those from the German Primate Center (DPZ)-Leibniz Institute for Primate Research in Germany, studied 10 therapeutic antibodies - Sotrovimab by GlaxoSmithKline; Tixagevimab and Cilgavimab (packaged in Evusheld) by AstraZeneca; Bebtelovimab and cocktail Bamlanivimab and Etesevimab by Eli Lilly; Casirivimab-Imdevimab by Regeneron; Regdanvimab by Celltrion, and S2H97.

The findings showed that only two were able to at least partially inhibit BA.2.12.1, BA.4, and BA.5 and that only one antibody, Bebtelovimab, efficiently blocked infection by all Omicron sub-variants.

Furthermore, the study shows that the BA.2.12.1 and especially BA.4 and BA.5 are inhibited worse than their predecessors BA.1 and BA.2 by antibodies generated after vaccination or inoculation followed by infection.

It is because the BA.2.12.1, BA.4, and BA.5 are immune escape variants. A pass-through infection with "old" Omicron sub-variants confers only limited protection against infection with "new" sub-variants, the researchers explained.

"These results confirm a trend that we have already seen in previous studies: Omicron sub-variants are not appreciably inhibited by most therapeutic antibodies and the few antibodies that inhibit frequently do so in a subvariant-specific fashion. Therefore, it is important to develop new antibodies in order to be prepared for future sub-variants," said Prerna Arora, first author from the German Primate Center.

Antibodies from unvaccinated individuals that were infected with BA.1 or BA.2 in spring 2022 neutralised BA.2.12.1 with similar efficiency but were much less potent against BA.4 and BA.5. Therefore, it is likely that a previous BA.1 or BA.2 infection provides little protection against a subsequent infection with BA.4 or BA.5.

Antibodies induced by three immunisations with the mRNA vaccine of BioNTech/Pfizer blocked all Omicron sub-variants. However, inhibition was less efficient as compared to that measured for a virus that circulated early during the pandemic, and inhibition of BA.2.12.1, BA.4, and BA.5 was less efficient as compared to BA.1 and BA.2.A

Similar results were obtained for antibodies induced upon vaccination plus breakthrough infection. Although this so-called hybrid immunity conferred overall higher neutralising activity against all variants tested, inhibition of BA.2.12.1, BA.4 and BA.5 was significantly reduced.

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