Coordinate Induction of Humoral and Spike Specific T-Cell Response in a Cohort of Italian Health Care Workers Receiving BNT162b2 mRNA Vaccine

Abstract

Vaccination is the main public health measure to reduce SARS-CoV-2 transmission and hospitalization, and a massive worldwide scientific effort resulted in the rapid development of effective vaccines. This work aimed to define the dynamics of humoral and cell-mediated immune response in a cohort of health care workers (HCWs) who received a two-dose BNT162b2-mRNA vaccination. The serological response was evaluated by quantifying the anti-RBD and neutralizing antibodies. The cell-mediated response was performed by a whole blood test quantifying Th1 cytokines (IFN-γ, TNF-α, IL-2), produced in response to spike peptides. The BNT162b2-mRNA vaccine induced both humoral and cell-mediated immune responses against spike peptides in virtually all HCWs without previous SARS-CoV-2 infection, with a moderate inverse relation with age in the anti-RBD response. Spike-specific T cells produced several Th1 cytokines (IFN-γ, TNF-α, and IL-2), which correlated with the specific-serological response. Overall, our study describes the ability of the BNT162b2 mRNA vaccine to elicit a coordinated neutralizing humoral and spike-specific T cell response in HCWs. Assessing the dynamics of these parameters by an easy immune monitoring protocol can allow for the evaluation of the persistence of the vaccine response in order to define the optimal vaccination strategy.

Keywords: SARS-CoV2; coordinate immunity; health care workers; mRNA vaccine; whole blood T cell assay.

Figure 1

Kinetic of humoral and cell-mediated immune response to vaccination. Legend to Figure 1: Longitudinal study (a,b). Serum and peripheral blood were collected before (T0) vaccination, 3 weeks after the 1st dose (T1), and 2 weeks after the 2nd dose (T2). (a) SARS-CoV-2 specific anti-N Abs and anti-RBD Abs were quantified in sera samples at each time point and showed as a box and whiskers graph. Anti-N-IgG are expressed as index values S/CO, and values ≥ 1.4 are considered positive; Anti-RBD-IgG are expressed as arbitrary units AU/mL and values ≥ 50 are considered positive. (b) Cytokines (IFN-γ, TNF-α, IL-2) were quantified in stimulated blood samples at each time point and shown as median after subtracting the background. Dashed lines identify the cut-off of each test calculated as the mean +/− 2SEM of 55 anti-S and anti-N negative HCWs before vaccination. Results are shown as box and whiskers graphs. ****: p < 0.0001; *: p < 0.5.

Figure 2

Coordinated immune response to vaccination. Legend to Figure 2: Cross-sectional study (a–f). (a) SARS-CoV-2 specific anti-N and anti-RBD Abs were analyzed at T2 in 169 HCWs; a microneutralization assay (MNA₉₀) was also performed in a subgroup of the enrolled HVWs (n = 73). Results are shown as box and whiskers graphs. (b) The correlation between the anti-RBD antibody titer and MNA₉₀ is shown (n = 73); (c) Cytokines (IFN-γ, TNF-α, IL-2) were quantified in stimulated blood samples at T2 (n = 169); (d) The correlation between the levels of IFN-γ and TNF-α and between IFN-γ and IL-2 are shown (n = 169). Each black dot represents one sample (e) The correlations between the level of IFN-γ and anti-RBD antibody titers and between the level of TNF-α and anti-RBD antibody titers are shown (n = 169). Each black dot represents one sample (f) The correlation between TNF-α and MNA₉₀ is shown (n = 73). Each black dot represents one sample.