The magnitude of the germinal center B cell and T follicular helper cell response predicts long-lasting antibody titers to plague vaccination.
The magnitude of the germinal center B cell and T follicular helper cell response predicts long-lasting antibody titers to plague vaccination.
复制标题
DOI：
10.3389/fimmu.2022.1017385
复制
发表时间：
2022
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
--
作者：
开发一种安全有效的疫苗来预防鼠疫耶尔森氏菌（鼠疫的病原体）仍然是全球卫生领域的一个重要优先事项。研究已经证明了针对鼠疫攻击的有效的基于免疫的保护，其由水性铝凝胶制剂中的鼠疫抗原亚单位疫苗接种诱导;然而，尚未完全证明该制剂和呈现中的这些候选疫苗是否以持久的细胞和抗体回忆应答的形式诱导持久的免疫记忆。在这项研究中，我们分析了在用各种佐剂配制的疫苗对小鼠进行F1 V和F1 + V鼠疫亚单位免疫后，生发中心T滤泡辅助细胞和生发中心B细胞的应答。我们的数据表明，与单独用铝胶佐剂配制的疫苗相比，用结合到铝胶佐剂的IL-2/GM-CSF细胞因子配制的重组鼠疫蛋白免疫在初次免疫后驱动生发中心T滤泡辅助细胞和生发中心B细胞应答的幅度增加。相反，鼠疫蛋白亚单位免疫与结合到铝胶的CpG ODN组合增加了加强免疫后生发中心Tfh和B细胞应答的幅度和持续时间。重要的是，增强的生发中心Tfh和B细胞应答与持久和高的F1 V特异性抗体滴度以及对F1 V再暴露的更稳健的抗体回忆应答相关。这些发现表明，驱动生发中心Tfh和B细胞应答增强的疫苗制剂对于诱导持久的免疫特异性体液免疫是至关重要的。
The development of a safe and effective vaccine against Yersinia pestis, the causative organism for plague disease, remains an important global health priority. Studies have demonstrated effective immune-based protection against plague challenge that is induced by plague antigen subunit vaccination in an aqueous alhydrogel formulation; however, whether these candidate vaccines in this formulation and presentation, induce long-lasting immunological memory in the form of durable cellular and antibody recall responses has not been fully demonstrated. In this study, we analyzed germinal center T follicular helper and germinal center B cell responses following F1V and F1 + V plague subunit immunization of mice with vaccines formulated in various adjuvants. Our data demonstrate that recombinant plague protein immunization formulated with IL-2/GM-CSF cytokines bound to alhydrogel adjuvant drive an increase in the magnitude of the germinal center T follicular helper and germinal center B cell responses following primary immunization, compared to vaccines formulated with Alhydrogel adjuvant alone. In contrast, plague protein subunit immunization combined with CpG ODN bound to alhydrogel increased the magnitude and duration of the germinal center Tfh and B cell responses following booster immunization. Importantly, enhanced germinal center Tfh and B cell responses correlated with long-lasting and high F1V-specific antibody titers and more robust antibody recall responses to F1V re-exposure. These findings indicate that vaccine formulations that drive enhancement of the germinal center Tfh and B cell responses are critical for inducing durable plague-specific humoral immunity.