BNT162b2 induces SARS-CoV-2-neutralising antibodies and T cells in humans

Abstract

BNT162b2, a lipid nanoparticle (LNP) formulated nucleoside-modified messenger RNA (mRNA) encoding the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein (S) stabilized in the prefusion conformation, has demonstrated 95% efficacy to prevent coronavirus disease 2019 (COVID-19). Recently, we reported preliminary BNT162b2 safety and antibody response data from an ongoing placebo-controlled, observer-blinded phase 1/2 vaccine trial1. We present here antibody and T cell responses from a second, non-randomized open-label phase 1/2 trial in healthy adults, 19-55 years of age, after BNT162b2 prime/boost vaccination at 1 to 30 µg dose levels. BNT162b2 elicited strong antibody responses, with S-binding IgG concentrations above those in a COVID-19 human convalescent sample (HCS) panel. Day 29 (7 days post-boost) SARS-CoV-2 serum 50% neutralising geometric mean titers were 0.3-fold (1 µg) to 3.3-fold (30 µg) those of the HCS panel. The BNT162b2-elicited sera neutralised pseudoviruses with diverse SARS-CoV-2 S variants. Concurrently, in most participants, S-specific CD8+ and T helper type 1 (TH1) CD4+ T cells had expanded, with a high fraction producing interferon-γ (IFNγ). Using peptide MHC multimers, the epitopes recognised by several BNT162b2-induced CD8+ T cells when presented on frequent MHC alleles were identified. CD8+ T cells were shown to be of the early-differentiated effector-memory phenotype, with single specificities reaching 0.01-3% of circulating CD8+ T cells. In summary, vaccination with BNT162b2 at well tolerated doses elicits a combined adaptive humoral and cellular immune response, which together may contribute to protection against COVID-19.

Neutralization of N501Y mutant SARS-CoV-2 by BNT162b2 vaccine-elicited sera

“…neutralization of Y501 virus by BNT162b2-elicited human sera is consistent with preserved neutralization of a panel of 15 pseudoviruses bearing spikes with other mutations found in circulating SARS-CoV-2 strains 7. …”

Immunity to SARS-CoV-2: Lessons Learned

“…Similar immune response kinetics immediately postvaccination have been observed and noted in data published from human clinical trials of late-stage COVID-19 vaccine candidates using spike protein as antigen: spike-protein-specific neutralizing antibodies were elicited by vaccination, and the titers peaked 7-14 days postcompletion of the vaccination series, and in most cases, these humoral responses were comparable with those observed in the respective panels of convalescent patient sera (46)(47)(48). Robust antigen-specific CD4+ and CD8+ T cell responses were observed with the BNT162b2 mRNA vaccine and the mRNA-1273 vaccine (47,49,50); notably both vaccines induce strong T-helper type 1 (Th1) CD4+ T cell responses with minimal to no T-helper type 2 (Th2) responses (49,50). T cell-mediated responses have also been reported for 3 Ad-based vaccines: chimpanzee ChAd-Ox1 n-CoV-19, Ad5-vectored COVID-19 vaccine and recombinant (r) Ad26 and rAd5 vector-based vaccine (48,(51)(52)(53).…”

Comorbid illnesses are associated with altered adaptive immune responses to SARS-CoV-2

“…SARS-CoV vaccine studies in mouse models have revealed the detrimental effect of imbalanced Th1 and Th2 immunity (47,48). By contrast, mRNA-1273 and BNT162b2 have been shown to be highly effective against SARS-CoV-2 and induce minimal Th2 immunity (49,50). Our data reveal important nuances in this paradigm, including the preferential expansion of highly polyfunctional T cells targeting S1 in hospitalized subjects that express IL-4/5/13, TNF, CD40L, and IL-2 in the presence or absence of IFN-γ ( Figure 3A and Supplemental Figure 6A).…”