Neutralization of SARS-CoV-2 variants by convalescent and BNT162b2 vaccinated serum

Abstract

SARS-CoV-2 and its variants continue to infect hundreds of thousands every day despite the rollout of effective vaccines. Therefore, it is essential to understand the levels of protection that these vaccines provide in the face of emerging variants. Here, we report two demographically balanced cohorts of BNT162b2 vaccine recipients and COVID-19 patients, from which we evaluate neutralizing antibody titers against SARS-CoV-2 as well as the B.1.1.7 (alpha) and B.1.351 (beta) variants. We show that both B.1.1.7 and B.1.351 are less well neutralized by serum from vaccinated individuals, and that B.1.351, but not B.1.1.7, is less well neutralized by convalescent serum. We also find that the levels of variant-specific anti-spike antibodies are proportional to neutralizing activities. Together, our results demonstrate the escape of the emerging SARS-CoV-2 variants from neutralization by serum antibodies, which may lead to reduced protection from re-infection or increased risk of vaccine breakthrough.

Fig. 1. Serum antibody levels of BNT162b2 vaccine recipients and potency of sera to neutralize SARS-CoV-2 variants.

a Serum antibody levels (EC50) that recognize the spike RBD of the wild-type USA-WA1/2020 (WA1) (Blue circles), B.1.1.7 (Orange squares), and B.1.351 (Green triangles) variants are shown. The RBD-B.1.1.7 carries the N501Y mutation, the only RBD mutation present in the B.1.1.7 variant. The RBD-B.1.351 has the K417N, E484K, and N501Y mutations which are the only three RBD mutations present in the B.1.351 variant. n = 51 biologically independent samples. b Comparison of neutralization titers (FRNT50) between WA1, B.1.1.7 (P = 0.0351) and B.1.351 (P = 0.0089) for BNT162b2 vaccinee sera. n = 50 biologically independent samples. c Correlation of variant matched RBD-specific antibody levels and neutralization titers (FRNT50) of the WA1 virus and the two variants. d, e Correlations between neutralization titers of the B.1.1.7 (d) and B.1.351 (e) variants with the WA1 virus. The dotted diagonal lines indicate identical neutralization, and the solid diagonal black lines indicate 10-fold differences in neutralization. f–h Correlation between participant age and neutralization titer against WA1 (f) (P < 0.0001), B.1.1.7 (g) (P < 0.0001), and B.1.351 (h) (P < 0.0001). n = 50 biologically independent samples. i Effect of age range 20–50 years (blue triangle) and >50 years (red inverted triangle) on the neutralization potency among the BNT162b2 vaccine recipients (WA1,B.1.1.7 P < 0.0001, B.1.351 P = 0.0001). n = 25 biologically independent samples per age group. For a, b, f–i, data are presented as the mean ± SD of log transformed values; P values are two-sided and include a Šidák multiple comparison correction. All experiments were performed in duplicate.

Fig. 2. Neutralization of SARS-CoV-2 variants by convalescent serum.

a Quantification of serum antibody levels (EC50) that recognize RBD protein corresponding to the wild-type (WA1)(blue circles), B.1.1.7 (orange squares), and B.1.351 (green triangles) variants. n = 50 biologically independent samples. Data are presented as the mean ± SD of log transformed values. b Comparison of neutralization titers between WA1, B.1.1.7, and B.1.351 for convalescent sera. n = 44 biologically independent samples. c Relationship between convalescent antibody levels and neutralization (FRNT50) of the different viral variants. d, e Correlations between convalescent serum neutralization titer of the B.1.1.7 (d) and B.1.351 (e) variants with the WA1 virus. The dotted diagonal lines indicate identical neutralization, and the solid diagonal black lines indicate 10-fold differences in neutralization. f Violin plots indicating FRNT50 values for WA1 (blue), B.1.1.7 (orange), and B.1.351 (green), stratified by the number of days between the date of confirmatory COVID-19 PCR test and the date of serum sample collection. Black bars indicate median FRNT50 for each group. For a, b, f P values are two-sided and include a Šidák multiple comparison correction. All experiments were performed in duplicate.