BNT162b2 vaccine induces neutralizing antibodies and poly-specific T cells in humans

Abstract

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Rapid determination of the wide dynamic range of SARS-CoV-2 Spike T cell responses in whole blood of vaccinated and naturally infected

“…Figure 1B shows that the two different assays detected a predominant Spike-specific response in all the individuals and defined a matching profile of Spike-specific T cell response after the prime and boost vaccination doses. The number of IFN-γ spots detected after boost vaccination matches that observed in the phase 1/2 trial of individuals vaccinated with BNT162b2 (13) and with a similar preparation consisting of the trimerized secreted version of the Spike receptor-binding domain (BNT162b1) (10), including a trial conducted in Chinese individuals vaccinated with BNT162b1 (21). While stimulation with the NP-specific peptide pool remained largely negative, the IFN-γ quantities in blood and the number of IFN-γ spots showed identical peak responses that occurred 7-10 days after the first dose in individuals V4 and V5, and 7-10 days after the second dose in individuals V1, V3 and V6.…”

“…We compared the Spike-specific T cell response detected at similar time points 2-3 months post vaccine boost or viral clearance. Unlike reports of higher quantities of neutralizing antibodies in vaccinees (13), individuals with symptomatic SARS-CoV-2 infection and vaccinees mount an equivalent magnitude of Spike-specific T cell response (both IFN-γ and IL-2 secretion) while higher levels of IFN-γ secretion were only detected in individuals who had an asymptomatic SARS-CoV-2 infection (Figure 5B). The latter observation is in line with previous analysis of asymptomatic and symptomatic SARS-CoV-2 infected individuals within 1 month of viral clearance where the former showed increased cytokine production with comparable frequencies of virus-specific T cells (5).…”

“…There were however some minor discrepancies. CRA did not detect the boost of Spike-specific T cells induced by the second vaccine dose in subjects V4 and V5, perhaps in relation to the transient lymphopenia induced by mRNA vaccination (13). IL-2 cytokine measurement (Figure 1C) depicted an equivalent pattern of Spike-specific T cell response with that obtained through IFN-γ release.…”

“…While experimental data has shown that high levels of neutralizing antibodies can be sufficient to protect from experimental infection, lower levels require the presence of T cells (1). The level of neutralizing antibody titers are however extremely heterogeneous after natural infection(12) and while most of the new SARS-CoV-2 vaccines induce high neutralizing antibody levels (13), their persistence over time needs to be evaluated. Instead, virus-specific T cells appear to persist for a long time after viral clearance (i.e.…”

BNT162b2-elicited neutralization of B.1.617 and other SARS-CoV-2 variants

“…Thus, reductions in neutralization like those observed in this study have not been demonstrated to result in loss of vaccine efficacy against disease. BNT162b2 elicits not only neutralizing antibodies, but also spike-specific CD4 + and CD8 + T cells and non-neutralizing antibody-dependent cytotoxicity, which can also serve as immune effectors 27,28 . Because neutralization titers do not measure all potentially protective vaccine responses, they cannot substitute for studies of vaccine efficacy and real-world effectiveness of COVID-19 vaccines against variants.…”