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SARS-CoV-2 spike-specific T_FH cells exhibit unique responses in infected and vaccinated individuals.

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.

SUBMITTER: He R

PROVIDER: S-EPMC10558553 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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SARS-CoV-2 spike-specific TFH cells exhibit unique responses in infected and vaccinated individuals.

He Rongzhang R Zheng Xingyu X Zhang Jian J Liu Bo B Wang Qijie Q Wu Qian Q Liu Ziyan Z Chang Fangfang F Hu Yabin Y Xie Ting T Liu Yongchen Y Chen Jun J Yang Jing J Teng Shishan S Lu Rui R Pan Dong D Wang You Y Peng Liting L Huang Weijin W Terzieva Velislava V Liu Wenpei W Wang Youchun Y Li Yi-Ping YP Qu Xiaowang X

Signal transduction and targeted therapy 20231006 1

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 (TFH) cells. However, the longevity and functional role of TFH 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+ TFH cell a ...[more]

PMID: 37802996

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Project description:BackgroundAs there are limited data on B cell epitopes for the nucleocapsid protein in SARS-CoV-2, we sought to identify the immunodominant regions within the N protein, recognized by patients with varying severity of natural infection with the Wuhan strain (WT), delta, omicron and in those who received the Sinopharm vaccines, which is an inactivated, whole virus vaccine.MethodsUsing overlapping peptides representing the N protein, with an in-house ELISA, we mapped the immunodominant regions within the N protein, in seronegative (n=30), WT infected (n=30), delta infected (n=30), omicron infected+vaccinated (n=20) and Sinopharm (BBIBP-CorV) vaccinees (n=30). We then investigated the sensitivity and specificity of these immunodominant regions and analysed their conservation with other SARS-CoV-2 variants of concern, seasonal human coronaviruses and bat Sarbecoviruses. We then investigated the kinetics of responses to these regions in those with varying severity of acute COVID-19.ResultsWe identified four immunodominant regions aa 29-52, aa 155-178, aa 274 to 297 and aa 365 to 388, were highly conserved within SARS-CoV-2 and the bat coronaviruses. The magnitude of responses to these regions varied based on the infecting SARS-CoV-2 variants, with WT infected individuals predominantly recognizing aa155 to 178 regions, delta infected individuals and vaccinated+omicron infected individuals predominantly recognizing regions aa 29 to 52 and aa 274 to 294 regions. Sinopharm vaccinees recognized all four regions, with the magnitude of responses significantly lower than other groups. >80% of individuals gave responses above the positive cut-off threshold to many of the four regions, with some differences with individuals who were infected with different VoCs. These regions were found to be 100% specific, as none of the seronegative individuals gave any responses.ConclusionsN-protein specific responses appear to be detectable in over 90% of those who were naturally infected or vaccinated with a whole virus inactivated vaccine, with responses mainly directed against four regions of the protein, which were highly conserved. As these regions were highly specific with high sensitivity, they have a potential to be used to develop diagnostic assays and to be used in development of vaccines.

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SARS-CoV-2 spike-specific T_FH cells exhibit unique responses in infected and vaccinated individuals.

Publications

SARS-CoV-2 spike-specific T<sub>FH</sub> cells exhibit unique responses in infected and vaccinated individuals.

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