SARS-CoV-2 501Y.V2 escapes neutralization by South African COVID-19 donor plasma

Abstract

SARS-CoV-2 501Y.V2 (B.1.351), a novel lineage of coronavirus causing COVID-19, contains substitutions in two immunodominant domains of the spike protein. Here, we show that pseudovirus expressing 501Y.V2 spike protein completely escapes three classes of therapeutically relevant antibodies. This pseudovirus also exhibits substantial to complete escape from neutralization, but not binding, by convalescent plasma. These data highlight the prospect of reinfection with antigenically distinct variants and foreshadows reduced efficacy of spike-based vaccines. Individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), develop neutralizing antibodies that can persist for months 1,2. Neutralizing antibodies are considered the primary correlate of protection from infection and are being pursued as therapeutics 3,4. Interim analyses with monoclonal neutralizing antibodies have shown success, facilitating their authorization for emergency use 5,6. The SARS-CoV-2 receptor binding domain (RBD) exists in either an 'up' (receptor-accessible) or 'down' (receptor-shielded) conformation. RBD is the dominant neutralization target for this and other human coronaviruses 7,8. These antibodies can be broadly divided into four main classes, of which two overlap with the angiotensin converting enzyme 2 (ACE2) receptor binding site (Fig. 1a and Supplementary Fig. 1a) 9. Class 1 antibodies are most frequently elicited in SARS-CoV-2 infection and include a public antibody response to an epitope only accessible in the RBD 'up' conformation 10. Class 2 antibodies use more diverse VH-genes and bind to RBD 'up' and RBD 'down' conformations of spike. After RBD, the N-terminal domain (NTD) of spike is the next most frequently targeted by neutralizing antibodies, most of which target a single immunodominant site 11. We, and others, recently described a new SARS-CoV-2 lineage in South Africa, defined as Nextstrain clade 20H/501Y.V2 (PANGOLin lineage B.1.351) 12. This lineage is defined by nine

Increased mortality among individuals hospitalised with COVID-19 during the second wave in South Africa

“…Preliminary data suggest that SARS-CoV-2 501Y.V2 may be more transmissible than other lineages (2,6) and escape the immune response from preceding infection with old SARS-CoV-2 lineages. (7,8) The United Kingdom reported increased hospitalisation and mortality rates in people infected with variant B.1.1.7 compared to infection with non-B.1.1.7 viruses. (9,10) There are currently limited data on the severity of lineage 501Y.V2.…”

mRNA vaccination boosts cross-variant neutralizing antibodies elicited by SARS-CoV-2 infection

“…Mutations found in emergent S variants decrease sensitivity to neutralization by mAbs, convalescent plasma, and sera from vaccinated individuals (27,37,58,(61)(62)(63)(64)(65)(66)(67)(68)(69)(70). As a result, there is concern that these and other emerging variants can evade neutralizing antibody responses generated during infection with variants circulating earlier in the pandemic and also from neutralizing antibody responses elicited by vaccines based on the spike protein of the Wuhan-Hu-1 variant.…”

Structural impact on SARS-CoV-2 spike protein by D614G substitution

“…It is therefore likely to be a superior immunogen for eliciting protective neutralizing antibody responses, which appear largely to target the RBD and NTD (39,42). It may also be an excellent scaffold for designing next-generation vaccines against new variants that have become resistant to protections offered by the existing vaccines (43)(44)(45)(46). In summary, we suggest that the enhanced infectivity of the G614 virus largely results from the increased stability of the S trimer, rather than the better exposed RBDs.…”