Prophylactic herpes simplex virus type 2 vaccine adjuvanted with a universal CD4 T cell helper peptide induces long-term protective immunity against lethal challenge in mice
Prophylactic herpes simplex virus type 2 vaccine adjuvanted with a universal CD4 T cell helper peptide induces long-term protective immunity against lethal challenge in mice
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预防性单纯疱疹病毒 2 型疫苗辅以通用 CD4 T 细胞辅助肽，可诱导小鼠抵抗致命攻击的长期保护性免疫力
DOI：
10.1016/j.intimp.2018.05.024
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发表时间：
2018
影响因子：
5.6
通讯作者：
Xiang Tianxin
中科院分区：
文献类型：
--
作者：
Li Xiaoquan;Zhang Shouhua;Lei Jun;Zhu Ying;Zhou Xin;Xiao Juhua;Xiang Tianxin
在入口处诱导稳健和长期的免疫应答仍然是HSV-2疫苗开发的一大挑战。在疫苗中采用CD 4 T细胞辅助肽被认为有利于增强免疫应答，然而，其对HSV-2疫苗的作用尚未研究。在本研究中，我们设计了一种同时表达HSV-2 gD胞外域和通用CD 4 T细胞辅助肽（TpD）的DNA疫苗（gD-TpD），并在小鼠模型上测试了其效力。用gD-TpD或对照DNA制剂免疫小鼠3次，然后休息直至第150天，此时用致死剂量的HSV-2经阴道攻击小鼠。我们的数据表明，gD-TpD显着增加gD特异性IgG和伊加在血清和阴道冲洗液。此外，增加的抗体应答显示增强的体外中和活性。此外，gD-TpD诱导平衡的Th 1/2细胞应答和CD 8（+）T细胞依赖性CTL活性。虽然在最终免疫后免疫应答随时间下降，但在gD-TpD组中，在病毒攻击后诱导了稳健和快速的抗体和T细胞应答。此外，gD-TpD在免疫小鼠中提供了针对致死病毒攻击的完全保护。总之，我们的研究结果表明，在HSV-2 gD亚单位疫苗中包含CD 4 T细胞辅助肽TpD可以诱导长期保护性免疫，为针对HSV-2甚至其他病毒的疫苗的合理设计提供信息。
Induction of robust and long-term immune responses at the portal of entry remains a big challenge for HSV-2 vaccine development. The adoption of a CD4 T cell helper peptide in the vaccine is thought to be beneficial for the enhancement of immune responses, however, its effect on HSV-2 vaccines has not yet been studied. In this study, we designed a DNA vaccine (gD-TpD) simultaneously expressing HSV-2 gD ectodomain and a universal CD4 T cell helper peptide (TpD), and tested its efficacy on a murine model. Mice were immunized 3 times with gD-TpD or control DNA formulations, and then were rested until Day 150 when they were vaginally challenged with lethal doses of HSV-2. Our data showed that gD-TpD significantly increased gD-specific IgG and IgA in both sera and vaginal washes. Furthermore, the increased antibody responses showed enhanced neutralization activity in vitro. In addition, gD-TpD induced balanced Th1/2 cellular responses and CD8(+) T cell-dependent CTL activity. Although immune responses dropped over time after the final immunization, robust and rapid antibody and T cell responses were induced upon virus challenge in gD-TpD group. Moreover, gD-TpD provided full protection against lethal viral challenge in immunized mice. Together, our findings indicate that the inclusion of the CD4 T cell helper peptide TpD in HSV-2 gD subunit vaccine could induce long-term protective immunity, providing information for a rational design of vaccines against HSV-2 or even other viruses.