Evidence for retained spike-binding and neutralizing activity against emerging SARS-CoV-2 variants in serum of COVID-19 mRNA vaccine recipients

Abstract

Background: 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.

Methods: We used a panel of 30 post-mRNA vaccination sera to determine neutralization and RBD and spike binding activity against a number of emerging viral variants. The virus neutralization was determined using authentic SARS-CoV-2 clinical isolates in an assay format that mimics physiological conditions.

Findings: We tested seven currently circulating viral variants of concern/interest, including the three Iota sublineages, Alpha (E484K), Beta, Delta and Lambda in neutralization assays. We found only small decreases in neutralization against Iota and Delta. The reduction was stronger against a sub-variant of Lambda, followed by Beta and Alpha (E484K). Lambda is currently circulating in parts of Latin America and was detected in Germany, the US and Israel. Of note, reduction in a receptor binding domain and spike binding assay that also included Gamma, Kappa and A.23.1 was negligible.

Interpretation: 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.

Funding: This work is part of the PARIS/SPARTA studies funded by the NIAID Collaborative Influenza Vaccine Innovation Centers (CIVIC) contract 75N93019C00051. In addition, this work was also partially funded by the Centers of Excellence for Influenza Research and Surveillance (CEIRS, contract # HHSN272201400008C), the JPB Foundation, the Open Philanthropy Project (research grant 2020-215611 (5384), by anonymous donors and by the Serological Sciences Network (SeroNet) in part with Federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. 75N91019D00024, Task Order No. 75N91020F00003.

Keywords: Antibodies; COVID-19; COVID-19 mRNA vaccines; Neutralization activity; SARS-CoV-2 variants; VoC.

Fig. 1

Phylogenetic relationships of the seven SARS-CoV-2 isolates selected. The time-calibrated tree contains a total of 10,605 background sequences in addition to the seven PSP-MSHS isolates. Viral variants of concern (VoC): Alpha, Beta and Gamma. Viral variants of interest (VoI): Iota, Lambda. Of note the Lambda isolate represents a subvariant with additional mutations relative to the main Lambda variant.

Fig. 2

Neutralizing activity of post-mRNA vaccination sera against different VoIs and VoCs. a: Absolute neutralization titers against the respective variant SARS-CoV-2 isolates. The geometric mean titers (GMT) with the 95% confidence intervals are depicted for each viral variant. A mixed effect analysis with Dunnett's multiple comparisons test was used for statistical analysis. NS: not significant, *: P <  0.05; **: P <  0.01 b: Fold reduction of geometric mean neutralization titers as compared to the wild type reference WA1 isolate. The grey connecting line identifies a given serum sample. A list of specific mutations found in the spike region of the clinical isolates tested can be found in Supplementary Table 2.

Fig. 3

Neutralizing activity of post-mRNA vaccination sera relative to pre-existing immunity or vaccine type a and b: Absolute neutralization titers of sera from participants that were seronegative prior to vaccination (a) and participants that were seropositive prior to vaccination (b). Individual data points depicting the absolute neutralization titers for each sample against the respective variant viruses are shown. Error bars depict the GMT with 95% confidence intervals. c and d: Absolute neutralization titers of sera from that received two doses of the Pfizer vaccine (c) or the Moderna vaccine (d). Individual data points depicting the absolute neutralization titers for each sample against the respective variant viruses are shown. Error bars depict the GMT with 95% confidence intervals. A mixed effect analysis with Dunnett's multiple comparisons test was used for statistical analysis in all four panels. NS: not significant, *: P <  0.05; **: P <  0.01; ***: P <  0.001; ***: P <  0.0001

Fig. 4

Binding activity of post-mRNA vaccination sera against RBD and spike proteins of different VoIs and VoCs. a and c show absolute area under the curve (AUC) binding values against various RBD and spike proteins. The geometric mean titers (GMT) with the 95% confidence intervals are depicted for each protein. One way Anova analysis with Dunnett's multiple comparisons test was used for statistical analysis. NS: not significant, *: P <  0.05 b and d show fold-reduction in binding as compare to the Washington derived wild type proteins.