SARS-CoV-2 variant B.1.1.7 is susceptible to neutralizing antibodies elicited by ancestral Spike vaccines

Abstract

The SARS-CoV-2 Spike glycoprotein mediates virus entry and is a major target for neutralizing antibodies. All current vaccines are based on the ancestral Spike with the goal of generating a protective neutralizing antibody response. Several novel SARS-CoV-2 variants with multiple Spike mutations have emerged, and their rapid spread and potential for immune escape have raised concerns. One of these variants, first identified in the United Kingdom, B.1.1.7 (also called VUI202012/01), contains eight Spike mutations with potential to impact antibody therapy, vaccine efficacy and risk of reinfection. Here we employed a lentivirus-based pseudovirus assay to show that variant B.1.1.7 remains sensitive to neutralization, albeit at moderately reduced levels (~2-fold), by serum samples from convalescent individuals and recipients of two different vaccines based on ancestral Spike: mRNA-1273 (Moderna), and protein nanoparticle NVX-CoV2373 (Novavax). Some monoclonal antibodies to the receptor binding domain (RBD) of Spike were less effective against the variant while others were largely unaffected. These findings indicate that B.1.1.7 is not a neutralization escape variant that would be a major concern for current vaccines, or for an increased risk of reinfection.

COVA1-18 neutralizing antibody protects against SARS-CoV-2 in three preclinical models

“…1a, Extended Data Table 1). These results were corroborated in multiple independent labs and COVA1-18 was also equipotent against the D614G variant (Extended Data Table 1) that now dominates worldwide [17][18][19][20][21] as well as the recently emerged B.1.1.7 variant that includes the N501Y mutation 8,9 . COVA1-18 bound strongly to SARS-CoV-2 S protein and showed no cross-reactivity with S proteins of SARS-CoV, MERS-CoV and common cold coronaviruses HKU1-CoV, 229E-CoV and NL63-CoV (Extended Data Fig.…”

“…Here, we evaluated the prophylactic and therapeutic effect of COVA1-18 in vivo, a neutralizing antibody isolated from a convalescent patient 7 and highly potent against the B.1.1.7. isolate 8,9 . In both prophylactic and therapeutic settings, SARS-CoV-2 remained undetectable in the lungs of COVA1-18 treated hACE2 mice.…”

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…”

The emergence and ongoing convergent evolution of the N501Y lineages coincides with a major global shift in the SARS-CoV-2 selective landscape

“…The deletion of codon S/144 in the N-terminal domain of Spike in these sequences appears to be strongly protective against some monoclonal antibodies 26,29 and the S982A mutation that they carry can be slightly protective against some Pfizer and Moderna vaccine induced antibodies 49 . Nevertheless, only very modest reductions have been observed in the capacity of polyclonal sera from vaccinated individuals to neutralize V1 pseudotyped viruses, suggesting that V1 likely has limited immune escape adaptations 24,25,55,56 . Furthermore, V1, V2 and V3 signature mutations (including N501Y) were overrepresented in in vitro experimental evolution lines not exposed to any active immunity, suggesting that many of the apparent immune-evasion signature mutations in all of these lineages might contribute to increased R0 irrespective of their immune evasion properties 57 .…”