The effect of spike mutations on SARS-CoV-2 neutralization

Abstract

Multiple SARS-CoV-2 vaccines have shown protective efficacy, which is most likely mediated by neutralizing antibodies recognizing the viral entry protein, Spike. As new SARS-CoV-2 variants are rapidly emerging, exemplified by the B.1.1.7, B.1.351 and P.1 lineages, it is critical to understand if antibody responses induced by infection with the original SARS-CoV-2 virus or current vaccines remain effective. In this study we evaluate neutralization of a series of mutated Spike pseudotypes based on divergence from SARS-CoV and then compare neutralization of the B.1.1.7 Spike pseudotype and individual mutations. Spike-specific monoclonal antibody neutralization was dramatically reduced, in contrast, polyclonal antibodies from patients infected in early 2020 remained active against most mutated Spike pseudotypes, however potency was reduced in a minority of samples. This work highlights that changes in the SARS-CoV-2 Spike can alter neutralization sensitivity and underlines the need for effective real-time monitoring of emerging mutations and their impact on vaccine efficacy.

Reduced sensitivity of infectious SARS-CoV-2 variant B.1.617.2 to monoclonal antibodies and sera from convalescent and vaccinated individuals

“…The B.1.1.7 variant was first identified in the UK, B.1.351 in South Africa and the P.1 lineage in Brazil [7][8][9][10][13][14][15] . They harbour mutations that enhance Spike affinity to ACE2, such as N501Y, which is present in the three variants and K417N/T found in B.1.351 and P.1 10,[16][17][18][19][20][21] . Antibody escape mutations in the RBD include E484K found in B.1.351 and P.1 10,[16][17][18][19][20][21] .…”

“…They harbour mutations that enhance Spike affinity to ACE2, such as N501Y, which is present in the three variants and K417N/T found in B.1.351 and P.1 10,[16][17][18][19][20][21] . Antibody escape mutations in the RBD include E484K found in B.1.351 and P.1 10,[16][17][18][19][20][21] . Another variant termed B.1.247/B.1.429 was originally detected in California.…”

A Reliable Indirect ELISA Protocol for Detection of Human Antibodies Directed to SARS-CoV-2 NP Protein

“…Active screening for novel and efficient antivirals, continuous surveillance of new variants, mass COVID-19 vaccination, and evaluation of the seroprevalence status of populations all are key to cope with the pandemic over the next few months [ 2 , 13 , 29 , 30 ]. Several reports demonstrated the emergence of new SARS-CoV-2 variants carrying mutations mainly in the viral S gene/protein [ 22 , 25 , 31 ]. Recent evidences proposed resistance of some of these variants to S-based vaccine-induced antibodies [ 23 , 25 , 26 ].…”

“…Several reports demonstrated the emergence of new SARS-CoV-2 variants carrying mutations mainly in the viral S gene/protein [ 22 , 25 , 31 ]. Recent evidences proposed resistance of some of these variants to S-based vaccine-induced antibodies [ 23 , 25 , 26 ]. Furthermore, accumulation of a mutation on the S gene/protein may affect the performance of some laboratory assays that specifically target this region [ 27 ].…”

“…Hence, in order to distinguish between immunized people due to vaccination from those recovered for the infection, S-based ELISA should be combined with reliable NP-based immunoassays. Moreover, most SARS-CoV-2 new variants carry mutations/deletions in the viral S gene [ 22 , 23 , 24 , 25 , 26 ]. Although there is a lack of conclusive evidence that these mutations/deletions can influence the accuracy of S-based serological testing, this possibility still exists, as their effects on S-based vaccine efficiency were reported [ 23 , 24 , 25 , 26 , 27 ].…”