Mito
Member
- Joined
- Dec 10, 2016
- Messages
- 2,554
“In summary, A.30 exhibits a cell line preference not observed for other viral variants and efficiently evades neutralization by antibodies elicited by ChAdOx1 nCoV-19 or BNT162b2 vaccination. SARS-CoV-2 entry into cell lines depends on S protein activation by the cellular proteases cathepsin L or TMPRSS2 [8], and activation by the latter is thought to support viral spread in the lung. Therefore, it is noteworthy that enhanced A.30 entry was observed for cell lines with cathepsin L (Vero, 293 T, Huh-7, A549 cells)—but not TMPRSS2 (Calu-3, Caco-2)-dependent entry [8]. Thus, one could speculate that A.30 might use cathepsin L with increased efficiency and slight (but not statistically significant) resistance of A.30 against the cathepsin L inhibitor MDL 28170 supports this possibility (Supplemental information, Fig. S1c). Notably, robust entry into cell lines was combined with high resistance against antibodies induced upon ChAdOx1 nCoV-19 or BNT162b2 vaccination. Neutralization resistance exceeded that of the Beta (B.1.351) variant, which is markedly neutralization resistant in cell culture and, in comparison with the Alpha (B.1.1.7) variant, is less well inhibited by the ChAdOx1 nCoV-19 vaccine [9]. Nevertheless, heterologous ChAdOx1 nCoV-19/BNT162b2 vaccination, which was previously shown to augment neutralizing antibody responses against VOCs compared to corresponding homologous vaccinations [7, 10], might offer robust protection against the A.30 variant. Collectively, our results suggest that the SARS-CoV-2 variant A.30 can evade control by vaccine-induced antibodies and might show an increased capacity to enter cells in a cathepsin L-dependent manner, which might particularly aid in the extrapulmonary spread. As a consequence, the potential spread of the A.30 variant warrants close monitoring and rapid installment of countermeasures.”