The emergence of SARS-CoV-2 variants harboring mutations in the spike (S) protein has raised concern about potential immune escape. Here, we studied humoral and cellular immune responses to wild type SARS-CoV-2 and the B.1.1.7 and B.1.351 variants of concern in a cohort of 121 BNT162b2 mRNA-vaccinated health care workers (HCW). Twenty-three HCW recovered from mild COVID-19 disease and exhibited a recall response with high levels of SARS-CoV-2-specific functional antibodies and virus-specific T cells after a single vaccination. Specific immune responses were also detected in seronegative HCW after one vaccination, but a second dose was required to reach high levels of functional antibodies and cellular immune responses in all individuals. Vaccination-induced antibodies cross-neutralized the variants B.1.1.7 and B.1.351, but the neutralizing capacity and Fc-mediated functionality against B.1.351 was consistently 2-to 4-fold lower than to the homologous virus. In addition, peripheral blood mononuclear cells were stimulated with peptide pools spanning the mutated S regions of B.1.1.7 and B.1.351 to detect cross-reactivity of SARS-CoV-2-specific T cells with variants. Importantly, we observed no differences in CD4+ T-cell activation in response to variant antigens, indicating that the B.1.1.7 and B.1.351 S proteins do not escape T-cell-mediated immunity elicited by the wild type S protein. In conclusion, this study shows that some variants can partially escape humoral immunity induced by SARS-CoV-2 infection or BNT162b2 vaccination, but S-specific CD4+ T-cell activation is not affected by the mutations in the B.1.1.7 and B.1.351 variants.
Bibliographical noteFunding Information:
This work was financially supported by the Top Sector Life Sciences & Health; Health~Holland (grant EMCLHS20017: DG, LG. RDdV), the European Union?s Horizon 2020 research and innovation program under grant No. 101003589 (RECoVER: BBOM, MPGK), ZonMW (grant agreement No. 10150062010005: BBOM, MPGK; and No. 10150062010008: BLH), the Netherlands Organization for Scientific Research (NWO) Vici grant (RWS), the Bill & Melinda Gates Foundation grant INV-002022 (RWS), and an Amsterdam UMC AMC Fellowship (MJvG). Author contributions: Conceptualization RDdV, CHGvK Formal Analysis DG, MCS, RDdV, CHGvK Funding acquisition MJvG, RWS, BLH, RLdS, MPGK, RSvB, RDdV, CHGvK Investigation DG, MCS, SB, GdH, LG, NNN, KSS, LCR, GS, AC, DvM, BBOM, RM, RSvB, RDdV Project administration SB, JATvO, ED, RDdV, CHGvK Resources TGC, MJvG, RWS, HJdJ, BLH, RDdV, CHGvK Supervision RWS, BLH, RLdS,
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