- May 2021
Since publication, the FDA has rescinded its authorisation of bamlanivimab (LY-CoV555), due to its lack of efficacy against circulating variants of concern, particularly B.1.351 (South African), as a result of E484K substitution A,B. Eli Lilly are now pursuing the use of their combination therapy of bamlanivimab with etesevimab (LY-CoV016).
The antibody cocktail REGN-CoV2 showed sustained efficacy against tested variant strains and thus remains a viable treatment option. However, a mutational library scan by Starr et al. revealed that a single amino acid change (E406W) is all that is required for a future variant to escape this therapy C.
Circulating variants highlight the limited efficacy of monoclonal antibodies to an evolving virus, particularly in those which are restricted to the RBD. A diverse panel of monoclonal antibodies, which bind subdominant epitopes may be a more sustainable approach.
A – Wang, P et al. Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7. 2021. Nature. https://doi.org/10.1038/s41586-021-03398-2
B – Starr, T.N.et al. Complete map of SARS-CoV-2 RBD mutations that escape the monoclonal LY-CoV555 and its cocktail with LY-CoV016. 2021. Cell Reports Medicine. https://doi.org/10.1016/j.xcrm.2021.100255
C – Starr, T.N.et al. Prospective mapping of viral mutations that escape antibodies used to treat COVID-19. 2021. Science. https://doi.org/10.1126/science.abf9302
- Mar 2021
Wang, P., Nair, M. S., Liu, L., Iketani, S., Luo, Y., Guo, Y., Wang, M., Yu, J., Zhang, B., Kwong, P. D., Graham, B. S., Mascola, J. R., Chang, J. Y., Yin, M. T., Sobieszczyk, M., Kyratsous, C. A., Shapiro, L., Sheng, Z., Huang, Y., & Ho, D. D. (2021). Antibody Resistance of SARS-CoV-2 Variants B.1.351 and B.1.1.7. Nature, 1–9. https://doi.org/10.1038/s41586-021-03398-2