Weak SARS-CoV-2-specific responses of TIGIT-expressing CD8+ T cells in people living with HIV after a third dose of a SARS-CoV-2 inactivated vaccine

Abstract

Abstract Background: T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domains (TIGIT), an inhibitory receptor expressed on T cells, plays a dysfunctional role in antiviral infection and antitumor activity. However, it is unknown whether TIGIT expression on T cells influences the immunological effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) inactivated vaccines. Methods: Forty-five people living with HIV (PLWH) on antiretroviral therapy (ART) for more than two years and 31 healthy controls (HCs), all received a third dose of a SARS-CoV-2 inactivated vaccine, were enrolled in this study. The amounts, activation, proportion of cell subsets, and magnitude of the SARS-CoV-2-specific immune response of TIGIT+CD4+ and TIGIT+CD8+ T cells were investigated before the third dose but 6 months after the second vaccine dose (0W), 4 weeks (4W) and 12 weeks (12W) after the third dose. Results: Compared to that in HCs, the frequency of TIGIT+ CD8+ T cells in the peripheral blood of PLWH increased at 12W after the third dose of the inactivated vaccine, and the immune activation of TIGIT+CD8+ T cells also increased. A decrease in the ratio of both T naïve (TN) and central memory (TCM) cells among TIGIT+CD8+ T cells and an increase in the ratio of the effector memory (TEM) subpopulation were observed at 12W in PLWH. Interestingly, particularly at 12W, a higher proportion of TIGIT+CD8+ T cells expressing CD137 and CD69 simultaneously was observed in HCs than in PLWH based on the activation-induced marker assay. Compared with 0W, SARS-CoV-2-specific TIGIT+CD8+ T-cell responses in PLWH were not enhanced at 12W but were enhanced in HCs. Additionally, at all time points, the SARS-CoV-2-specific responses of TIGIT+CD8+ T cells in PLWH were significantly weaker than those of TIGIT–CD8+ T cells. However, in HCs, the difference in the SARS-CoV-2-specific responses induced between TIGIT+CD8+ T cells and TIGIT–CD8+ T cells was insignificant at 4W and 12W, except at 0W. Conclusions: TIGIT expression on CD8+ T cells may hinder the T-cell immune response to a booster dose of an inactivated SARS-CoV-2 vaccine, suggesting weakened resistance to SARS-CoV-2 infection, especially in PLWH. Furthermore, TIGIT may be used as a potential target to increase the production of SARS-CoV-2-specific CD8+ T cells, thereby enhancing the effectiveness of vaccination.