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

Abstract

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 mutations found in the B.1.1.7 Spike protein. The vaccine sera exhibited a broad range of neutralizing titres against the wild-type pseudoviruses (<1:4 to 3449) that were reduced against B.1.1.7 variant by 3.85 fold (IQR 2.68-5.28). This reduction was also evident in sera from some convalescent patients. Decreased B.1.1.7 neutralization was also observed with monoclonal antibodies targeting the N-terminal domain (9 out of 10), the Receptor Binding Motif (RBM) (5 outof 29), but not in neutralizing mAbs binding outside the RBM. Introduction of the E484K mutation in a B.1.1.7 background led to a further loss of neutralizing activity by vaccine-elicited antibodies over that conferred by the B.1.1.7 mutations alone. Further work is needed to establish the impact of these observations on protective vaccine efficacy in the context of the evolving B.1.1.7 lineage that will likely acquire E484K.

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).…”

“…We therefore hypothesise that an increase in the efficiency of furin cleavage is an important contributing factor to the increase in transmission of these variants. The B.1.1.7 lineage continues to evolve and it is notable that several isolates have gained additional S mutations such as E484K which has been shown to cause a 9.6-fold decreased neutralisation by vaccine sera in a B.1.1.7 background (Collier et al, 2021), and which could further increase receptor binding avidity in combination with N501Y. E484K and N501Y together have been associated with other rapidly emerging variants of the B.1.351 and P.1 lineages.…”

“…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).…”

“…In an intense burst of research around this question, convalescent and post-vaccination sera have been used in neutralisation assays with B.1.1.7 live virus isolated from infected patients, recombinant viruses generated by reverse genetics and virus pseudotypes (PV) with some or all of the B.1.1.7 mutations in S, but results have been inconsistent. 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).…”

An observational cohort study on the incidence of SARS-CoV-2 infection and B.1.1.7 variant infection in healthcare workers by antibody and vaccination status

“…21 Reinfection rates following natural infection have not been shown to be higher in studies using SGTF as a proxy for B.1.1.7, 20,22 even though variably decreased sensitivity to neutralisation by monoclonal antibodies, convalescent plasma and sera from vaccinated individuals has been observed in vitro for B.1.1.7. [23][24][25][26][27][28][29][30][31][32][33][34] The Oxford-AstraZeneca trial showed good vaccine efficacy against sequencingconfirmed symptomatic B.1.1.7, despite evidence of decreased neutralising titres, but decreased efficacy for asymptomatic/unknown symptom infections. 35 Pfizer-BioNTech vaccine effectiveness in HCWs appears preserved despite increasing B.1.1.7 incidence in the UK; however these studies have not specifically investigated cases of SGTF or sequencing-confirmed B.1.1.7.…”