Reduced neutralizing activity of post-SARS-CoV-2 vaccination serum against variants B.1.617.2, B.1.351, B.1.1.7+E484K and a sub-variant of C.37

Abstract

Highly efficacious vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed. However, the emergence of viral variants that are more infectious than the earlier SARS-CoV-2 strains is concerning. Several of these viral variants have the potential to partially escape neutralizing antibody responses warranting continued immune-monitoring. Here, we tested a number of currently circulating viral variants of concern/interest, including B.1.526 (Iota), B.1.1.7+E484K (Alpha), B.1.351 (Beta), B.1.617.2 (Delta) and C.37 (Lambda) in neutralization assays using a panel of post-mRNA vaccination sera. The assays were performed with authentic SARS-CoV-2 clinical isolates in an assay that mimics physiological conditions. We found only small decreases in neutralization against B.1.526 and an intermediate phenotype for B.617.2. The reduction was stronger against a sub-variant of C.37, followed by B.1.351 and B.1.1.7+E484K. C.37 is currently circulating in parts of Latin America and was detected in Germany, the US and Israel. Of note, reduction in a binding assay that also included P.1, B.1.617.1 (Kappa) and A.23.1 was negligible. Taken together, these findings suggest that mRNA SARS-CoV-2 vaccines may remain effective against these viral variants of concern/interest and that spike binding antibody tests likely retain specificity in the face of evolving SARS-CoV-2 diversity.

Towards a population-based threshold of protection for COVID-19 vaccines

“…This protective level should be calculated from larger data sets from efficacious vaccines than those available to us and a consensus would need to be achieved on defining a single protective threshold. Although other studies of COP have focused on neutralization assays, we believe that the data within this report and other studies support the use of binding antibody which has many practical advantages [24] . Finally, the COP could be useful for supporting boosting recommendations as serum antibody concentrations wane and new virus variants cause rapid increases in the number of CoVID-19 cases.…”

Structure-activity relationships of B.1.617 and other SARS-CoV-2 spike variants

“…6A). The conformational changes in NTD loops and glycan shield provide an explanation for the escape from the NTD-specific nAbs 21 and the markedly reduced efficacies of the convalescent and vaccine-elicited sera 25,26 .…”

“…For instance, the Pfizer/BioNTech (BNT162b2) and Moderna (mRNA-1273) vaccines experience an astounding drop in protection (up to 12-fold) against the Beta variant while their protection against the Gamma variant is reduced by 2-to 3-fold 15,20,22 . While mRNA-1273 affords comparable protection against the Alpha variant compared to the wild-type (WT) Wuhan strain 20,[22][23][24] , a 2-to 3-fold reduction in protection against the Delta variant is reported 25,26 . In contrast, BNT162b2 generates substantially less neutralizing titers against the Delta variant compared to the Alpha variant 21,27 .…”

COVID-19 Infection in Children, Infants and Pregnant Subjects: An Overview of Recent Insights and Therapies

“…The Lambda variant results in being the most capable of reducing the efficacy of neutralising antibodies induced by mRNA vaccines (Pfizer and Moderna). It resulted in a 4.6-fold decrease in neutralizing antibodies, even higher than the Beta variant, already known for the capacity of the mutations to evade the immune system [137]. However, all vaccines demonstrated they kept their neutralizing capacity [136,138].…”