SARS-CoV-2 spike-specific TFH cells exhibit unique responses in infected and vaccinated individuals
Rongzhang He, Xingyu Zheng, Jian Zhang, Bo Liu, Qijie Wang, Qian Wu, Ziyan Liu, Fangfang Chang, Yabin Hu, Ting Xie, Yongchen Liu, Jun Chen, H. J. Yang, Shishan Teng, Rui Lü, Dong Pan, You Wang, Liting Peng, Weijin Huang, Velislava Terzieva, Wenpei Liu, Youchun Wang, Yi‐Ping Li, Xiaowang Qu, Yi‐Ping Li, Xiaowang Qu
Abstract
Abstract Long-term humoral immunity to SARS-CoV-2 is essential for preventing reinfection. The production of neutralizing antibody (nAb) and B cell differentiation are tightly regulated by T follicular help (T FH ) cells. However, the longevity and functional role of T FH cell subsets in COVID-19 convalescents and vaccine recipients remain poorly defined. Here, we show that SARS-CoV-2 infection and inactivated vaccine elicited both spike-specific CXCR3 + T FH cell and CXCR3 − T FH cell responses, which showed distinct response patterns. Spike-specific CXCR3 + T FH cells exhibit a dominant and more durable response than CXCR3 − T FH cells that positively correlated with antibody responses. A third booster dose preferentially expands the spike-specific CXCR3 + T FH cell subset induced by two doses of inactivated vaccine, contributing to antibody maturation and potency. Functionally, spike-specific CXCR3 + T FH cells have a greater ability to induce spike-specific antibody secreting cells (ASCs) differentiation compared to spike-specific CXCR3 − T FH cells. In conclusion, the persistent and functional role of spike-specific CXCR3 + T FH cells following SARS-CoV-2 infection and vaccination may play an important role in antibody maintenance and recall response, thereby conferring long-term protection. The findings from this study will inform the development of SARS-CoV-2 vaccines aiming to induce long-term protective immune memory.