Functional Analysis of Spike from SARS-CoV-2 Variants Reveals the Role of Distinct Mutations in Neutralization Potential and Viral Infectivity.

Enhanced viral transmission and escape from vaccine-elicited neutralizing antibodies drive worldwide spread of SARS-CoV-2 variants and promote disease progression. However, the impact of specific spike mutations that are carried by different viral variants on viral infectivity and neutralization sensitivity has not been completely defined. Here, we use pseudoviruses to assess the contribution of spike mutations within the Receptor Binding Domain (RBD) and the Furin Cleavage Site (FCS), and appear in circulating viral variants, on viral infectivity and neutralization potential against sera that was drawn from fully vaccinated individuals. Our functional analysis demonstrates that single, P681H, P681R or A701V-FCS mutations do not play a role in viral infectivity and neutralization potential. However, when in conjunction with the RBD-N501Y mutation, viral infectivity is enhanced. Similarly, combining the E484K-RBD mutation to the spike that carries FCS mutations reduces neutralization sensitivity with no effects on viral infectivity. Employing a similar approach onto the spike from Delta or Lota SARS-CoV-2 variants further reveals that specific RBD mutations affect neutralization sensitivity or viral infectivity differently. Our results validate the efficacy of the Pfizer third dose vaccine against Delta and Lota SARS-CoV-2 variants, and outline the significance of distinct RBD mutations in promoting viral infectivity and neutralization sensitivity to post-vaccination sera.

SARS CoV-2 Delta variant exhibits enhanced infectivity and a minor decrease in neutralization sensitivity to convalescent or post-vaccination sera.

Since their identification, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Kappa and Delta have rapidly spread to become globally dominant. However, their infectivity and sensitivity to administered vaccines have not been documented. We monitored the neutralization potential of convalescent or BNT162b2 post-vaccination sera against Kappa and Delta SARS-CoV-2 pseudoviruses. We show that both variants were successfully neutralized by convalescent and post-vaccination sera, exhibiting a mild decrease in their neutralization sensitivity. Of the two variants, Delta presented enhanced infectivity levels compared with Kappa or wild-type SARS-CoV-2. Nevertheless, both variants were not as infectious or resistant to post-vaccination sera as the Beta variant of concern. Interestingly, the Delta plus variant (AY.1/B.1.617.2.1) exhibited high resistance to post-vaccination sera, similar to that of the Beta SARS-CoV-2. However, its infectivity levels were close to those of wild-type SARS-CoV-2. These results account for the worldwide prevalence of Delta variant of concern and confirm the efficacy of the BNT162b2 vaccine against circulating other Delta variants.