Antibody longevity and cross-neutralizing activity following SARS-CoV-2 wave 1 and B.1.1.7 infections

Abstract

As SARS–CoV–2 variants continue to emerge globally, a major challenge for COVID–19 vaccination is the generation of a durable antibody response with cross–neutralizing activity against both current and newly emerging viral variants. Cross–neutralizing activity against major variants of concern (B.1.1.7, P.1 and B.1.351) has been observed following vaccination, albeit at a reduced potency, but whether vaccines based on the Spike glycoprotein of these viral variants will produce a superior cross–neutralizing antibody response has not been fully investigated. Here, we used sera from individuals infected in wave 1 in the UK to study the long-term cross-neutralization up to 10 months post onset of symptoms (POS), as well as sera from individuals infected with the B.1.1.7 variant to compare cross–neutralizing activity profiles. We show that neutralizing antibodies with cross-neutralizing activity can be detected from wave 1 up to 10 months POS. Although neutralization of B.1.1.7 and B.1.351 is lower, the difference in neutralization potency decreases at later timepoints suggesting continued antibody maturation and improved tolerance to Spike mutations. Interestingly, we found that B.1.1.7 infection also generates a cross-neutralizing antibody response, which, although still less potent against B.1.351, can neutralize parental wave 1 virus to a similar degree as B.1.1.7. These findings have implications for the optimization of vaccines that protect against newly emerging viral variants.

SERS-based assay for multiplexed detection of cross-reactivity and persistence of antibodies against the spike of the native, P.1 and B.1.617.2 SARS-CoV-2 in non-hospitalised adults

“…45,47,48 Whereas the extent of immune resistance of VOCs to binding antibodies varies considerably, the lower cross-reactivity of antibodies against VOCs has been widely reported in previous studies. For example, a prior study by Dupont et al detected remarkably high sera IgG and IgM neutralisation escape of the B.1.617.2 spike in the variantnaïve convalescent sera, 46 and the results not only aligned with more recent findings, 4 but also supported the reduced antibody-VOCs responses observed in this study.…”

mRNA-1273 and BNT162b2 COVID-19 vaccines elicit antibodies with differences in Fc-mediated effector functions

“…Despite the remarkable efficacy of the mRNA vaccines against SARS-CoV-2 D614G, waves of variants have emerged that include amino acid substitutions that diminish neutralizing antibody activity (28)(29)(30). Among the VOCs, the mRNA vaccines appear to neutralize Alpha (B.1.1.7) (31) and Gamma (P.1) with only a minimal loss of activity, but exhibit compromised neutralizing activity against the Beta (B.1.351) variant (32,33). Yet, whether Fc responses were equally affected across the VOCs remains unclear.…”

DataSheet_1.pdf

“…The B.1.1.7 and B.1.351, first detected in December 2020 in the UK (42) and South Africa (43), respectively, quickly spread worldwide since extensive mutations on the spike enhanced viral transmission. Our and other emerging studies (44,45) showed that antibodies raised against the D614G lineage cross-neutralized the two VOCs but at reduced potency, that was marked for the B.1.351 variant. These evidences pointed out the urgent need to implement currently available vaccine formulations to protect against newly emerging VOC.…”