Indian SARS-CoV-2 Variant Evades Antibodies Induced by Infection and Vaccination

A novel SARS-CoV-2 variant B.1.617 first detected in India harbors eight mutations of which seven located within the S1 subunit{three in the N-terminal domain (R21T, E154K, Q218H), two in the RBD (L452R, E484Q), and two between the RBD and the S1/S2 border (D614G, P681R)} and one mutation is located within the S2 subunit (H1101D) in the spike protein showed resistance against therapeutic antibody Bamlanivimab and diminished antibody neutralization by vaccine and plasma therapy.

The study was carried out using in vitro cell studies, protein assays, and statistical analysis of the plasma activity of infected and vaccinated individuals. The S protein of variant B.1.617 showed enhanced entry into human intestinal (Caco-2) and lung cell (Calu-3) lines when compared to the wild type. But the entry of the B.1.617 variant could be blocked by RBD inhibitors like soluble ACE2 and a serine-protease inhibitor Camostat which blocks TMPRSS2, a transmembrane protein that mediates the fusion of viral and cell membrane. It was also observed that B.1.617 was resistant against the therapeutic antibody Bamlanivimab and moderately resistant to Casirivimab and the antibody cocktail of Bamlanivimab and Etesevimab. In contrast, B.1.351 and B.1.617 S protein-mediated entry was efficiently inhibited by Imdevimab and by a cocktail of Casirivimab and Imdevimab.

Convalescent plasma therapy and mRNA vaccine Comirnaty/BNT162b2 has been able to successfully neutralize antibodies against wild-type SARS-CoV-2. Analyzing the neutralization by plasma samples of two to three weeks old vaccinees after the second dose and COVID-19 patients showed that variant B.1.617 can partially evade antibody-mediated inhibition induced by vaccines and plasma respectively. From these outcomes, it could be concluded that the B.1.617 variant could be treated more efficiently by entry blockers ACE2 and Camostat and by therapeutic antibody  Imdevimab and by a cocktail of Casirivimab and Imdevimab when compared to mRNA vaccine and plasma therapy and Bamlanivimab monotherapy.

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