Immunodominant SARS‐CoV‐2‐specific CD4⁺ and CD8⁺ T‐cell responses elicited by inactivated vaccines in healthy adults

Abstract

Safety profiles and humoral responses to inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines have been previously assessed, but cellular immune responses to inactivated SARS-CoV-2 vaccines remain understudied. Here, we report the comprehensive characteristics of SARS-CoV-2-specific CD4⁺ and CD8⁺ T-cell responses elicited by the BBIBP-CorV vaccine. A total of 295 healthy adults were recruited, and SARS-CoV-2-specific T-cell responses were detected after stimulation with overlapping peptide pools spanning the entire length of the envelope (E), membrane (M), nucleocapsid (N), and spike (S) proteins. Robust and durable CD4⁺ (p < 0.0001) and CD8⁺ (p < 0.0001) T-cell responses specific to SARS-CoV-2 were detected following the third vaccination, with an increase in specific CD8⁺ T-cells, compared to CD4⁺ T-cells. Cytokine profiles showed that interferon gamma and tumor necrosis factor-α were predominantly expressed with the negligible expression of interleukin (IL)-4 and IL-10, indicating a Th1- or Tc1-biased response. Compared to E and M proteins, N and S activated a higher proportion of specific T-cells with broader functions. The predominant frequency of the N antigen (49/89) was highest for CD4⁺ T-cell immunity. Furthermore, N_19-36 and N_391-408 were identified to contain dominant CD8⁺ and CD4⁺ T-cell epitopes, respectively. In addition, N_19-36 -specific CD8⁺ T-cells were mainly effector memory CD45RA cells, whereas N_391-408 -specific CD4⁺ T-cells were mainly effector memory cells. Therefore, this study reports comprehensive features of T-cell immunity induced by the inactivated SARS-CoV-2 vaccine BBIBP-CorV and proposes highly conserved candidate peptides which may be beneficial in vaccine optimization.