BNT162b2 vaccine induces divergent B cell responses to SARS-CoV-2 S1 and S2

• Published in: Nature immunology Vol. 23; no. 1; pp. 33 - 39
• Main Authors: Brewer, R. Camille, Ramadoss, Nitya S., Lahey, Lauren J., Jahanbani, Shaghayegh, Robinson, William H., Lanz, Tobias V.
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.01.2022; Nature Publishing Group
• Subjects: 631/250/2152/2153/1291; 631/250/2152/2153/1571; 631/250/590/2293; Antibodies; Antibodies, Neutralizing - blood; Antibodies, Neutralizing - immunology; Antibodies, Viral - blood; Antibodies, Viral - immunology; B-Lymphocytes - immunology; Biomedical and Life Sciences; Biomedicine; BNT162 Vaccine - immunology; Coronaviruses; COVID-19; COVID-19 - immunology; COVID-19 - prevention & control; Humans; Immunoglobulin A; Immunoglobulin A - blood; Immunoglobulin A - immunology; Immunoglobulin G; Immunoglobulin G - blood; Immunoglobulin G - immunology; Immunological memory; Immunology; Infectious Diseases; Letter; Lymphocytes B; Memory cells; Memory T Cells - immunology; mRNA vaccines; Protein Domains - immunology; Proteins; SARS-CoV-2 - immunology; Severe acute respiratory syndrome coronavirus 2; Spike Glycoprotein, Coronavirus - immunology; Spike protein; Transcriptomics; Vaccine Efficacy; Vaccines
• ISSN: 1529-2908; 1529-2916
• DOI: 10.1038/s41590-021-01088-9

The first ever US Food and Drug Administration-approved messenger RNA vaccines are highly protective against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 1 – 3 . However, the contribution of each dose to the generation of antibodies against SARS-CoV-2 spike (S) protein and the degree of protection against novel variants warrant further study. Here, we investigated the B cell response to the BNT162b2 vaccine by integrating B cell repertoire analysis with single-cell transcriptomics pre- and post-vaccination. The first vaccine dose elicits a recall response of IgA + plasmablasts targeting the S subunit S2. Three weeks after the first dose, we observed an influx of minimally mutated IgG + memory B cells that targeted the receptor binding domain on the S subunit S1 and likely developed from the naive B cell pool. This response was strongly boosted by the second dose and delivers potently neutralizing antibodies against SARS-CoV-2 and several of its variants. Lanz and colleagues show that the first dose of the BNT162b2 mRNA vaccine against SARS-CoV-2 activates a non-neutralizing recall response predominantly targeting the S2 subunit of the spike protein, while the second dose boosts neutralizing antibodies specific for the receptor binding domain of the spike protein.