Infection- and vaccine-induced antibody binding and neutralization of the B.1.351 SARS-CoV-2 variant

Abstract

The emergence of SARS-CoV-2 variants with mutations in the spike protein is raising concerns about the efficacy of infection- or vaccine-induced antibodies. We compared antibody binding and live virus neutralization of sera from naturally infected and Moderna-vaccinated individuals against two SARS-CoV-2 variants: B.1 containing the spike mutation D614G and the emerging B.1.351 variant containing additional spike mutations and deletions. Sera from acutely infected and convalescent COVID-19 patients exhibited a 3-fold reduction in binding antibody titers to the B.1.351 variant receptor-binding domain of the spike protein and a 3.5-fold reduction in neutralizing antibody titers against SARS-CoV-2 B.1.351 variant compared to the B.1 variant. Similar results were seen with sera from Moderna-vaccinated individuals. Despite reduced antibody titers against the B.1.351 variant, sera from infected and vaccinated individuals containing polyclonal antibodies to the spike protein could still neutralize SARS-CoV-2 B.1.351, suggesting that protective humoral immunity may be retained against this variant.

Keywords: SARS-CoV-2; emerging variants; humoral immunity; receptor-binding domain; vaccine; viral neutralization.

Graphical abstract

Figure 1

RBD binding and neutralizing antibody response against SARS-CoV-2 B.1.351 variant in SARS-CoV-2-infected individuals Shown are data from the following cohorts based on natural infection: 19 acutely infected COVID-19 patients (5–19 days PSO; closed symbols), 30 convalescent COVID-19 individuals (1–3 months and 3–8 months PSO, closed symbols), and 18 healthy controls (open symbols). (A) IgG antibody responses against SARS-CoV-2 receptor-binding domain (RBD) were measured by an electrochemiluminescent multiplex immunoassay and reported as arbitrary units per ml (AU/mL) as normalized by a standard curve for the B.1 (black) and B.1.351 (red) SARS-CoV-2 variants. (B–D) (B) The 50% inhibitory titer (FRNT₅₀) on the focus reduction neutralization test (FRNT) for the B.1 (black) and B.1.351 (red) SARS-CoV-2 variants and correlations plots between the corresponding RBD and FRNT₅₀ for the (C) B.1 variant and (D) B.1.351 variant are shown for the acutely infected COVID-19 patients. (E) Comparison of IgG antibody responses between the B.1 (black) and B.1.351 (red) SARS-CoV-2 variants at 1-3 month and the B.1 (green) and B.1.351 (blue) SARS-CoV-2 variants at 3–8 month time points are shown for the convalescent COVID-19 patients. (F and G) Changes in IgG antibody responses over two time points through 8 months for the (F) B.1 (1–3 months [black] and 3-8 months [green]) and (G) B.1.351 (1–3 months [red] and 3–8 months [blue]) are shown for the convalescent COVID-19 patients. (H) Comparison of FRNT₅₀ titer between the B.1 (black) and B.1.351 (red) SARS-CoV-2 variants at 1–3 month time points and the B.1 (green) and B.1.351 (blue) SARS-CoV-2 variants at 3–8 month time points are shown for the convalescent COVID-19 patients. (I and J) Changes in FRNT₅₀ titers over two time points through 8 months for the (I) B.1 (1–3 months [black] and 3–8 months [green]) and (J) B.1.351 (1–3 months [red] and 3–8 months [blue]) are shown for the convalescent COVID-19 patients. (K and L) Spearman correlation plots between the corresponding RBD and FRNT₅₀ for the (K) B.1 variant (1–3 month [black] and 3–8 month [green]) and (L) B.1.351 variant (1–3 month [red] and 3–8 month [blue]) are shown for the convalescent COVID-19 patients. The dotted line in the RBD-binding assays represents the limit of detection (239 IgG AU/mL). The dotted line in the FRNT assays represents the maximum concentrations of the serum tested (1/20). Normality of the antibody binding and neutralization titers was determined using a Shapiro Wilk normality test. A non-parametric pairwise analysis for RBD-specific IgG titers and neutralization titers was performed by a Wilcoxon matched-pairs signed rank test. A Spearman rank test was used for the correlation analysis of the RBD-specific IgG AU/mL values against FRNT₅₀ titers.

Figure 2

RBD binding and neutralizing antibody response against SARS-CoV-2 B.1.351 viral variant among mRNA-1273-vaccinated individuals Shown are data from the individuals that received 100 μg of mRNA-1273 on day 14 post-2nd dose (>56 years or older, 19 participants; closed symbols) and 18 healthy controls (open symbols). (A) IgG antibody responses against SARS-CoV-2 receptor-binding domain (RBD) were measured by an electrochemiluminescent multiplex immunoassay and reported as arbitrary units per ml (AU/mL) as normalized by a standard curve for the B.1 (black) and B.1.351 (red) SARS-CoV-2 variants. (B–D) (B) The 50% inhibitory titer (FRNT₅₀) on the focus reduction neutralization test (FRNT) for the B.1 (black) and B.1.351 (red) SARS-CoV-2 variants and correlation plots between the corresponding RBD and FRNT₅₀ for the (C) B.1 variant and (D) B.1.351 variant are shown. The dotted line in the RBD binding assays represents the limit of detection (239 AU/mL). The dotted line in the FRNT assays represents the maximum concentrations of the serum tested (1/20). The GMT fold change for the respective isolates relative to B.1 is shown in each of the plots. Normality of the antibody binding and neutralization titers was determined using a Shapiro Wilk normality test. Non-parametric pairwise analysis for RBD specific IgG titers and neutralization titers was performed by a Wilcoxon matched-pairs signed rank test. A Spearman rank test was used for correlation analysis of the RBD-specific IgG AU/mL values against FRNT₅₀ titers.