SARS-CoV-2 B.1.1.7 sensitivity to mRNA vaccine-elicited, convalescent and monoclonal antibodies

TLDR

SARS‑CoV‑2 transmission remains uncontrolled worldwide, with the B.1.1.7 variant exhibiting higher transmissibility and raising uncertainty about whether vaccine responses to the prototypic strain will be affected by its mutations. The study aimed to evaluate immune responses elicited by the mRNA vaccine BNT162b2. Neutralising antibody responses were measured after a single immunisation using pseudoviruses bearing either the wild‑type Spike protein or the eight amino‑acid mutations present in the B.1.1.7 Spike. Neutralising titres from BNT162b2‑vaccinated individuals were broadly effective against wild‑type SARS‑CoV‑2 but were modestly reduced against the B.1.1.7 variant, a reduction also seen in some convalescent sera and with monoclonal antibodies targeting the N‑terminal domain and receptor‑binding motif; the addition of the E484K mutation to B.1.1.7 further diminished neutralisation by vaccine‑elicited antibodies and most mAbs, indicating a potential threat to vaccine efficacy.

Abstract

Abstract Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) transmission is uncontrolled in many parts of the world, compounded in some areas by higher transmission potential of the B1.1.7 variant now seen in 50 countries. It is unclear whether responses to SARS-CoV-2 vaccines based on the prototypic strain will be impacted by mutations found in B.1.1.7. Here we assessed immune responses following vaccination with mRNA-based vaccine BNT162b2. We measured neutralising antibody responses following a single immunization using pseudoviruses expressing the wild-type Spike protein or the 8 amino acid mutations found in the B.1.1.7 spike protein. The vaccine sera exhibited a broad range of neutralising titres against the wild-type pseudoviruses that were modestly reduced against B.1.1.7 variant. This reduction was also evident in sera from some convalescent patients. Decreased B.1.1.7 neutralisation was also observed with monoclonal antibodies targeting the N-terminal domain (9 out of 10), the Receptor Binding Motif (RBM) (5 out of 31), but not in neutralising mAbs binding outside the RBM. Introduction of the E484K mutation in a B.1.1.7 background to reflect newly emerging viruses in the UK led to a more substantial loss of neutralising activity by vaccine-elicited antibodies and mAbs (19 out of 31) over that conferred by the B.1.1.7 mutations alone. E484K emergence on a B.1.1.7 background represents a threat to the vaccine BNT162b.