SARS-CoV-2 specific T cell and humoral immune responses upon vaccination with BNT162b2: a 9 months longitudinal study

Abstract

The humoral and cellular immune responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) upon the coronavirus disease 2019 (COVID-19) vaccination remain to be clarified. Hence, we aimed to investigate the long-term chronological changes in SARS-CoV-2 specific IgG antibody, neutralizing antibody, and T cell responses during and after receiving the BNT162b2 vaccine. We performed serological, neutralization, and T cell assays among 100 hospital workers aged 22-73 years who received the vaccine. We conducted seven surveys up to 8 months after the second vaccination dose. SARS-CoV-2 spike protein-specific IgG (IgG-S) titers and T cell responses increased significantly following the first vaccination dose. The highest titers were observed on day 29 and decreased gradually until the end of the follow-up period. There was no correlation between IgG-S and T cell responses. Notably, T cell responses were detected on day 15, earlier than the onset of neutralizing activity. This study demonstrated that both IgG-S and T cell responses were detected before acquiring sufficient levels of SARS-CoV-2 neutralizing antibodies. These immune responses are sustained for approximately 6 to 10 weeks but not for 7 months or later following the second vaccination, indicating the need for the booster dose (i.e., third vaccination).

Figure 1

Humoral responses during and after BNT162b2 mRNA-based SARS-CoV-2 vaccination regimen. (A–C) Humoral responses on day 1 (immediately after the first dose) (n = 100), day 15 (n = 100), day 29 (7 days after the second dose) (n = 97), day 61 (n = 97), day 82–96 (n = 96), day 224–232 (n = 66), and day 263 (n = 19). IgG antibodies against SARS-CoV-2 spike protein (A), nucleocapsid (B), and IgM against spike protein (C) were measured using chemiluminescent microparticle immunoassay (CMIA). An ELISA-based semi-quantitative neutralization assay was also performed (D). Dashed lines indicate the cutoff for each assay. All data were represented as line graphs using GraphPad Prism 9.3.0. Black line indicates 4160 AU/mL as the cutoff, given that this threshold may correspond to a 95% probability of sufficient neutralizing activity.

Figure 2

SARS-CoV-2 spike specific IgG titers by background factors. Wald test was used to compare the mean differences of IgG-S-RBD titers between background factors at each time point using STATA version 17.0. (A) SARS-CoV-2 spike specific IgG titers by age (< 40 or ≥ 40 years), (B) SARS-CoV-2 spike specific IgG titers by sex (men or women), (C) SARS-CoV-2 spike specific IgG titers by BMI (< 25 or ≥ 25 kg/m²). SARS-CoV-2 spike specific IgG titers were measured on the following schedule: day 1 (immediately after the first dose) (n = 100), day 15 (n = 100), day 29 (7 days after the second dose) (n = 97), day 61 (n = 97), day 82–96 (n = 96), day 224–232 (n = 66), and day 263 (n = 19).

Figure 3

SARS-CoV-2 spike specific T cell response during and after BNT162b2 mRNA-based SARS-CoV-2 vaccination regimen. T cell responses on day 1 (immediately after the first dose) (n = 100), day 15 (n = 100), day 29 (7 days after the second dose) (n = 97), day 61 (n = 97), day 224–232 (n = 66), and day 263 (n = 14). The release of IFN-γ from stimulated CD4⁺ T cells (A) and both CD4⁺ and CD8⁺ T cells (B) with SARS-CoV-2 spike peptides using QuantiFERON SARS-CoV-2 RUO. All data were represented as line graphs using GraphPad Prism 9.3.0. Dashed lines indicate the cutoff for the assay.

Figure 4

Correlation between SARS-CoV-2 spike specific IgG titers and T cell responses at each time point. Spearman’s rank correlation test was conducted using STATA version 17.0. (A) Correlation between IgG-S-RBD titer and spike-specific CD4⁺ T-cell responses. (B) Correlation between IgG-S-RBD titer and spike-specific CD4⁺ and CD8⁺ T cell responses. The correlation was assessed at each time point: day 1 (immediately after the first dose) (n = 100), day 15 (n = 100), day 29 (7 days after the second dose) (n = 97), day 61 (n = 97), day 224–232 (n = 66), and day 263 (n = 14).