Translational Health, Molecular Medicine Division, International Centre for Genetic Engineering and Biotechnology, New Delhi, India.
Division of Virus Research and Therapeutics, CSIR-Central Drug Research Institute, Lucknow, India.
Front Immunol. 2023 Feb 28;14:1128784. doi: 10.3389/fimmu.2023.1128784. eCollection 2023.
While most vaccines aim to develop a solid humoral and neutralizing antibody response against the pathogen, an effective vaccine candidate should be able to stimulate both the B-cell mediated humoral immunity, and T-cell mediated cellular immunity. The focus of vaccinology is rapidly gaining to generate T cell responses, which can mediate pathogen clearance and help B cells leading to protective antibody responses. Here we evaluate the cellular immune response of the pre-clinical tetravalent dengue subunit vaccine candidate, DSV4, in mice. While we have shown previously that DSV4 induces type-specific neutralizing antibody responses in mice, in this study, we show that the vaccine candidate DSV4 well induces dengue-specific T- cell responses evaluated by their ability to produce IFN-γ. In addition to IFN-γ secretion by both CD4+ and CD8+ T-cells in immunized mice, we observed that DSV4 also induces a higher frequency and cytokine functions of follicular CD4+ helper T-cells (T). These cytokines lead to an efficient germinal center reaction and potent B cell antibody response. Apart from T response, DSV4 stimulated Type 1 T helper cells (T) which is characteristic of a viral infection leading to secretion of pro-inflammatory cytokines and phagocyte-dependent protective immune responses. Our study highlights that DSV4 can mediate both arms of adaptive immunity-humoral and cell-mediated immunity in mice. By elucidating vaccine-specific T cell response, our work has implications in showing DSV4 as an effective, type-specific and safe dengue vaccine candidate.
虽然大多数疫苗的目的是针对病原体产生坚实的体液和中和抗体反应，但有效的疫苗候选物应该能够刺激 B 细胞介导的体液免疫和 T 细胞介导的细胞免疫。疫苗学的重点正在迅速转向产生 T 细胞反应，这可以介导病原体清除，并帮助 B 细胞产生保护性抗体反应。在这里，我们评估了四价登革热亚单位疫苗候选物 DSV4 在小鼠中的细胞免疫反应。虽然我们之前已经表明 DSV4 在小鼠中诱导了针对特定类型的中和抗体反应，但在这项研究中，我们表明疫苗候选物 DSV4 可以很好地诱导登革热特异性 T 细胞反应，这可以通过它们产生 IFN-γ 的能力来评估。除了免疫小鼠中 CD4+和 CD8+T 细胞产生 IFN-γ外，我们还观察到 DSV4 还诱导了滤泡性 CD4+辅助 T 细胞（T）的更高频率和细胞因子功能。这些细胞因子导致有效的生发中心反应和有效的 B 细胞抗体反应。除了 T 反应外，DSV4 还刺激了 1 型辅助 T 细胞（T），这是病毒感染的特征，导致促炎细胞因子的分泌和吞噬细胞依赖的保护性免疫反应。我们的研究强调，DSV4 可以在小鼠中介导适应性免疫的两个方面——体液和细胞介导免疫。通过阐明疫苗特异性 T 细胞反应，我们的工作表明 DSV4 是一种有效、针对特定类型和安全的登革热疫苗候选物。
