Baba Satoshi, Hayashi Hiroki, Yoshida Shota, Yin Nanxiang, Shimamura Munehisa, Morishita Ryuichi, Rakugi Hiromi, Nakagami Hironori, Yamamoto Koichi
Department of Health Development and Medicine, Osaka University, Suita, Osaka, Japan.
Department of Geriatric Medicine, Osaka University, Suita, Osaka, Japan.
iScience. 2025 Apr 28;28(6):112542. doi: 10.1016/j.isci.2025.112542. eCollection 2025 Jun 20.
Follicular helper T (Tfh) cells are a subset of CD4 T cells that help B cells to produce high-affinity antibodies. Efficient Tfh cell induction by vaccines is critical for protective efficacy against diseases. A Tfh epitope, identified from the SARS-CoV-2 spike protein, has been shown to bind to the corresponding HLA and activates Tfh cells. Here, we assessed the efficacy of a peptide vaccine conjugated with SARS-CoV-2 Tfh epitope against experimental hypertension in a mouse model. The Tfh-angiotensin II (Tfh-Ang II) vaccine activated Tfh and germinal center B cells and induced antibodies against Ang II, thereby suppressing hypertension. However, Ang II-specific autoreactive T cells were not induced. Interestingly, Tfh-Ang II-induced antibody production was enhanced by SARS-CoV-2 spike priming. Moreover, human peripheral blood mononuclear cells from individuals vaccinated with COVID-19 mRNA vaccine were activated by Tfh epitope. Collectively, the SARS-CoV-2 spike-derived universal Tfh epitope may be effective for peptide-based vaccine development.
滤泡辅助性T（Tfh）细胞是CD4 T细胞的一个亚群，可帮助B细胞产生高亲和力抗体。疫苗有效诱导Tfh细胞对于疾病的保护效果至关重要。从严重急性呼吸综合征冠状病毒2（SARS-CoV-2）刺突蛋白中鉴定出的一个Tfh表位，已被证明可与相应的人类白细胞抗原（HLA）结合并激活Tfh细胞。在此，我们在小鼠模型中评估了与SARS-CoV-2 Tfh表位偶联的肽疫苗对实验性高血压的疗效。Tfh-血管紧张素II（Tfh-Ang II）疫苗激活了Tfh细胞和生发中心B细胞，并诱导产生了抗Ang II抗体，从而抑制了高血压。然而，并未诱导出Ang II特异性自身反应性T细胞。有趣的是，SARS-CoV-2刺突蛋白预激发增强了Tfh-Ang II诱导的抗体产生。此外，来自接种了2019冠状病毒病（COVID-19）信使核糖核酸（mRNA）疫苗个体的人外周血单个核细胞被Tfh表位激活。总体而言，SARS-CoV-2刺突蛋白衍生的通用Tfh表位可能对基于肽的疫苗开发有效。
