Humoral immune response to circulating SARS-CoV-2 variants elicited by inactivated and RBD-subunit vaccines

Abstract

SARS-CoV-2 variants could induce immune escape by mutations on the receptor-binding domain (RBD) and N-terminal domain (NTD). Here we report the humoral immune response to circulating SARS-CoV-2 variants, such as 501Y.V2 (B.1.351), of the plasma and neutralizing antibodies (NAbs) elicited by CoronaVac (inactivated vaccine), ZF2001 (RBD-subunit vaccine) and natural infection. Among 86 potent NAbs identified by high-throughput single-cell VDJ sequencing of peripheral blood mononuclear cells from vaccinees and convalescents, near half anti-RBD NAbs showed major neutralization reductions against the K417N/E484K/N501Y mutation combination, with E484K being the dominant cause. VH3-53/VH3-66 recurrent antibodies respond differently to RBD variants, and K417N compromises the majority of neutralizing activity through reduced polar contacts with complementarity determining regions. In contrast, the 242–244 deletion (242–244Δ) would abolish most neutralization activity of anti-NTD NAbs by interrupting the conformation of NTD antigenic supersite, indicating a much less diversity of anti-NTD NAbs than anti-RBD NAbs. Plasma of convalescents and CoronaVac vaccinees displayed comparable neutralization reductions against pseudo- and authentic 501Y.V2 variants, mainly caused by E484K/N501Y and 242–244Δ, with the effects being additive. Importantly, RBD-subunit vaccinees exhibit markedly higher tolerance to 501Y.V2 than convalescents, since the elicited anti-RBD NAbs display a high diversity and are unaffected by NTD mutations. Moreover, an extended gap between the third and second doses of ZF2001 leads to better neutralizing activity and tolerance to 501Y.V2 than the standard three-dose administration. Together, these results suggest that the deployment of RBD-vaccines, through a third-dose boost, may be ideal for combating SARS-CoV-2 variants when necessary, especially for those carrying mutations that disrupt the NTD supersite.

Platelet-driven coagulopathy in COVID-19 patients: in comparison to seasonal influenza cases

“…Those findings may point out another pathogenicity of COVID-19, although more evidences are needed. Concomitantly, pre-infection by influenza viruses can augment ACE2 expression, increasing further infectivity of SARS-CoV-2 and causing more severe pulmonary damage [ 30 ]. As the flu seasons overlap with COVID-19 pandemic, preventive measures and/or timely vaccinations against both respiratory viruses are imperative.…”

Possible Targets of Pan-Coronavirus Antiviral Strategies for Emerging or Re-Emerging Coronaviruses

“…Excitingly, several vaccines against SARS-CoV-2 have been granted an emergency use authorization, including BBIBP-CorV (Sinopharm) and CoronaVac (Sinovac) in China, the Pfizer-BioNTech COVID-19 vaccine (Pfizer) and the mRNA-1273 vaccine (Moderna) in the United States, and the Sputnik-V vaccine in Russia. Additionally, the protective rates and effectiveness of each vaccine are over 70% [ 81 , 82 , 83 , 84 , 85 ] against the early pandemic SARS-CoV-2 strains as well as the recently circulating strains, suggesting the disease can be controlled by vaccination in the future ( Table 2 ).…”

Structures of SARS-CoV-2 B.1.351 neutralizing antibodies provide insights into cocktail design against concerning variants

“…Structural analyses suggest that five of them directly antagonize the binding of ACE2, whereas the neutralization mechanisms of the other three do not depend on ACE2 blocking. Together with BD-515 and BD-623 that we described previously 4 , we have collected ten neutralizing antibodies that can potentially serve as prophylactics and…”

“…Also, studying the neutralizing mechanisms and binding epitopes of those mAbs is crucial for therapeutics and vaccine development. Recently, we investigated the humoral antibody responses of SARS-CoV-2 convalescent patients 7 and vaccinees towards circulating variants 4 . During this process, we identified a panel of mAbs that could efficiently neutralize the B.1.351 variant (Fig.…”