The SARS-CoV-2 spike L452R-E484Q variant in the Indian B.1.617 strain showed significant reduction in the neutralization activity of immune sera

摘要

To assess the impact of the key non-synonymous amino acid substitutions in the RBD of the spike protein of SARS-CoV-2 variant B.1.617.1 (dominant variant identified in the current India outbreak) on the infectivity and neutralization activities of the immune sera, L452R and E484Q (L452R-E484Q, “co-variant”) pseudotyped virus was constructed (with the D614G background). The impact on the binding with the neutralizing antibodies was also assessed by an ELISA assay. Pseudotyped virus carrying a L452R-E484Q co-variant showed a comparable infectivity compared with D614G. However, there was a significant reduction in the neutralization activity of the immune sera from non-human primates vaccinated with a recombinant Receptor binding domain (RBD) protein, convalescent patients, and healthy vaccinees vaccinated with an mRNA vaccine. In addition, there was a reduction in the binding of L452R-E484Q-D614G protein to the antibodies of the immune sera from vaccinated non-human primates. These results highlight the interplay between infectivity and other biologic factors involved in the natural evolution of SARS-CoV-2. Reduced neutralization activities against the L452R-E484Q co-variant will have impact to the health authorities planning and implications to the vaccination strategy/new vaccine development.