Antibodies elicited by SARS-CoV-2 infection or mRNA vaccines have reduced neutralizing activity against Beta and Omicron pseudoviruses

Abstract

Multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that possess mutations associated with increased transmission and antibody escape have arisen over the course of the current pandemic. Although the current vaccines have largely been effective against past variants, the number of mutations found on the Omicron (B.1.1.529) spike protein appear to diminish the protection conferred by pre-existing immunity. Using vesicular stomatitis virus (VSV) pseudoparticles expressing the spike protein of several SARS-CoV-2 variants, we evaluated the magnitude and breadth of the neutralizing antibody response over time in individuals after infection and in mRNA-vaccinated individuals. We observed that boosting increases the magnitude of the antibody response to wildtype (D614), Beta, Delta, and Omicron variants; however, the Omicron variant was the most resistant to neutralization. We further observed that vaccinated healthy adults had robust and broad antibody responses whereas responses may have been reduced in vaccinated pregnant women, underscoring the importance of learning how to maximize mRNA vaccine responses in pregnant populations. Findings from this study show substantial heterogeneity in the magnitude and breadth of responses after infection and mRNA vaccination and may support the addition of more conserved viral antigens to existing SARS-CoV-2 vaccines.

Emergence of SARS-CoV-2 Omicron (B.1.1.529) variant, salient features, high global health concerns and strategies to counter it amid ongoing COVID-19 pandemic

“…The analysis revealed that though boosting with third dose enhanced the neutralization capacity, however Omicron is most resistant to neutralization in comparison to other VOCs and the boosting remained unable to evoke high response in pregnant vaccinated women. The findings are suggestive of considerable heterogeneity in the magnitude and breadth of neutralization responses of Omicron in different groups ( Sievers et al, 2022 ). After 2 doses of Heterologous vaccination with CoronaVac vaccine there was no detectable Omicron neutralization but when boosted with BNT162b2, it showed 1.4 fold higher neutralization in comparison to 2 doses of mRNA vaccine ( Pérez-Then et al, 2022 ).…”

An mRNA vaccine candidate for the SARS-CoV-2 Omicron variant

“…Unlike other VOCs, Omicron harbors a large number of mutations, including more than 30 mutations on the spike protein, 15 of which are located within the receptor binding domain (RBD) 3 . As a consequence, Omicron gains the ability to extensively escape vaccine-and infection-elicited neutralizing antibodies in vitro 4,[5][6][7] , raising a serious concern about the efficacy of existing vaccines in a setting where Omicron circulates predominantly. It is therefore of significant importance to develop new vaccine candidates targeting the Omicron variant as a part of the preparedness plan.…”

Breakthrough infections after COVID-19 vaccination: Insights, perspectives and challenges

“…In the USA, by the end of January, over 90% of Covid cases were related to this variant, which has rapidly become the dominant circulating variant of concern [ 9 ] . The Omicron variant harbors a remarkable 59–amino acid substitution throughout its genome relative to the ancestral Wuhan-hu-1 SARS-CoV-2 virus, where almost 37 of these nonsynonymous mutations are located within the spike protein, the target of neutralizing antibodies against SARS-CoV-2 [ 10 ]. Overall, emerging data have suggested that the omicron variant presents increased transmissibility and ability to dodge immunity whether from vaccination or previous infection as well decreased pathogenicity [ 11 , 12 ].…”