Emerging SARS-CoV-2 variants reduce neutralization sensitivity to convalescent sera and monoclonal antibodies

Abstract

SARS-CoV-2 Spike-specific antibodies contribute the majority of the neutralizing activity in most convalescent human sera. Two SARS-CoV-2 variants, N501Y.V1 (also known as B.1.1.7 lineage or VOC-202012/01) and N501Y.V2 (B.1.351 lineage), reported from the United Kingdom and South Africa, contain several mutations in the receptor binding domain of Spike and are of particular concern. To address the infectivity and neutralization escape phenotypes potentially caused by these mutations, we used SARS-CoV-2 pseudovirus system to compare the viral infectivity, as well as the neutralization activities of convalescent sera and monoclonal antibodies (mAbs) against SARS-CoV-2 variants. Our results showed that N501Y Variant 1 and Variant 2 increase viral infectivity compared to the reference strain (wild-type, WT) in vitro. At 8 months after symptom onset, 17 serum samples of 20 participants (85%) retaining titers of ID50 >40 against WT pseudovirus, whereas the NAb titers of 8 samples (40%) and 18 samples (90%) decreased below the threshold against N501Y.V1 and N501Y.V2, respectively. In addition, both N501Y Variant 1 and Variant 2 reduced neutralization sensitivity to most (6/8) mAbs tested, while N501Y.V2 even abrogated neutralizing activity of two mAbs. Taken together the results suggest that N501Y.V1 and N501Y.V2 reduce neutralization sensitivity to some convalescent sera and mAbs.

Increased transmission of SARS-CoV-2 lineage B.1.1.7 (VOC 2020212/01) is not accounted for by a replicative advantage in primary airway cells or antibody escape

“…This is unsurprising given that there is no observed increase in reinfection reported with B.1.1.7 nor was there high seroprevalence in the UK during the emergence of this variant. Our finding is supported by many studies using B.1.1.7 viruses and PV which show either no reduction or a modest reduction in polyclonal serum titres (Collier et al, 2021;Diamond et al, 2021;Hu et al, 2021;Muik et al, 2021;Rees-Spear C et al, 2021;Wang et al, 2021;Wu et al, 2021). There is some evidence of heterogeneity of responses and neutralising titres for some individuals with initially low responses against WT virus can drop below limits of detection against the B.1.1.7 variant (Skelly et al, 2021).…”

“…In some studies, PV bearing B.1.1.7 and wildtype S showed equivalent (<2-fold) neutralisation by convalescent sera (Collier et al, 2021;Rees-Spear C et al, 2021) or sera raised against vaccines (Muik et al, 2021;Wu et al, 2021). However, other studies found a modest decreased susceptibility (up to 4-fold) of B.1.1.7 PV to convalescent sera (Hu et al, 2021;Wang et al, 2021) or vaccine sera (Collier et al, 2021). Sera raised against BNT162b2 vaccine did not show decreased ability to neutralise a recombinant virus with 3 key B.1.1.7 S mutations; ∆69-70 + N501Y + D614G (Xie et al, 2021).…”

Multiple SARS-CoV-2 variants escape neutralization by vaccine-induced humoral immunity

“…Of greatest concern has been the emergence of multiple strains of the B.1.351 lineage (also known as 501Y.V2), which were first reported in South Africa and have since spread globally (Tegally et al, 2021). This lineage bears three RBD mutations, K417N, E484K, and N501Y, in addition to several mutations outside of RBD, and several reports have suggested that convalescent and vaccinee sera have decreased cross-neutralization of B.1.351 lineage variants (Wang et al, 2021;Wibmer et al, 2021;Wu et al, 2021;Hu et al, 2021). A key limitation of several of these reports has been the use of single mutations or combinations of mutations that do not naturally occur.…”

Efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 variant of concern 202012/01 (B.1.1.7): an exploratory analysis of a randomised controlled trial

“…23 Early studies assessing the neutralising ability of sera from convalescent patients and vaccinees against pseudoviruses expressing some mutations present in B.1.1.7 or the entire B.1.1.7 spike protein suggest no or little reduction in neutralisation compared with older circulating viral variants. [24][25][26][27][28] Early reports suggest that vaccine efficacy might not be reduced against this variant. 4…”