Pan-Sarbecovirus Neutralizing Antibodies in BNT162b2-Immunized SARS-CoV-1 Survivors

Abstract

Emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern pose a challenge to the effectiveness of current vaccines. A vaccine that could prevent infection caused by known and future variants of concern as well as infection with pre-emergent sarbecoviruses (i.e., those with potential to cause disease in humans in the future) would be ideal. Here we provide data showing that potent cross-clade pan-sarbecovirus neutralizing antibodies are induced in survivors of severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) infection who have been immunized with the BNT162b2 messenger RNA (mRNA) vaccine. The antibodies are high-level and broad-spectrum, capable of neutralizing not only known variants of concern but also sarbecoviruses that have been identified in bats and pangolins and that have the potential to cause human infection. These findings show the feasibility of a pan-sarbecovirus vaccine strategy. (Funded by the Singapore National Research Foundation and National Medical Research Council.).

Figure 1. Boosting of Cross-Clade Pan-Sarbecovirus Neutralizing Antibodies.

Panel A shows the multiplex surrogate virus neutralization test (sVNT) analysis of five panels of human serum specimens against 10 different sarbecoviruses. All serum was used at a dilution of 1:20. A cutoff of 30% was set as previously determined. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was used as the reference for comparison. The serum panels were as follows: SARS-CoV-1–patient, serum specimens from survivors of SARS-CoV-1 infection; SARS-CoV-2–patient, serum specimens obtained during 2020 from patients with SARS-CoV-2 infection; healthy–vaccinated, serum specimens obtained from healthy persons at day 14 after the second dose of the BNT162b2 messenger RNA vaccine; SARS-CoV-2–vaccinated, serum specimens obtained from Covid-19 survivors who had received two doses of BNT162b2 vaccine; and SARS-CoV-1–vaccinated, serum specimens obtained from SARS-CoV-1 infection survivors 21 to 62 days after the first dose of BNT162b2 vaccine. Panel B shows titration of neutralizing antibodies expressed as the 50% neutralization titer (NT₅₀) with the use of the same serum panels and viruses as in Panel A. Specimens were tested at dilutions from 1:20 to 1:20,480 by means of serial titration. The SARS-CoV-1–vaccinated panel was used as the reference group. A cutoff of 1:100 is indicated by the dashed line. Panel C shows representative flow cytometry plots for the SARS-CoV-1–vaccinated panel (5 specimens), the healthy–vaccinated panel (6 specimens), and the SARS-CoV-2–vaccinated panel (5 specimens), indicating the frequency of cells positive for both SARS-CoV-1 and SARS-CoV-2. Panel D shows a plot of the frequency of cells positive for both SARS-CoV-1 and SARS-CoV-2 among all SARS-CoV-1–positive or SARS-CoV-2–positive cells. The SARS-CoV-1–vaccinated panel was used as the reference group. Box plots (Panels A, B, and D) show all data points; the whiskers indicate the range, the top and bottom of each box the 75th and 25th percentiles, and the horizontal line inside each box the 50th percentile. Significance was determined with a Wilcoxon signed-rank test. P values are indicated above each plot. A P value of less than 0.05 was considered to indicate statistical significance. Viruses from the SARS-CoV-1 clade are shaded in gray in Panels A and B.