Recombinant Rabies Virus Overexpressing OX40-Ligand Enhances Humoral Immune Responses by Increasing T Follicular Helper Cells and Germinal Center B Cells
Recombinant Rabies Virus Overexpressing OX40-Ligand Enhances Humoral Immune Responses by Increasing T Follicular Helper Cells and Germinal Center B Cells
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DOI：
10.3390/vaccines8010144
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发表时间：
2020-03-01
期刊：
影响因子：
7.8
通讯作者：
Wang, Yong
中科院分区：
文献类型：
--
作者：
Li, Yingying;Zhao, Ling;Wang, Yong
由狂犬病病毒（RABV）引起的狂犬病仍然是大多数国家公共卫生的严重威胁。研制有效的狂犬病疫苗是控制狂犬病传播的重要手段。共刺激因子OX 40-配体（OX 40 L）通过T-B细胞相互作用在T细胞依赖的体液免疫应答中起关键作用。本研究构建了过表达小鼠OX 40 L的重组RABV（LBNSE-OX 40 L），并在小鼠模型中评价了其对免疫原性的影响。与亲本病毒LBNSE免疫的小鼠相比，LBNSE-0X 40 L免疫的小鼠产生更多数量的T滤泡辅助（Tfh）细胞、生殖中心（GC）B细胞和浆细胞（PC）。此外，LBNSE-OX 40 L早在免疫后7天（dpi）就诱导了显著更高水平的病毒中和抗体（VNA），其持续8周，导致对小鼠的保护比LBNSE（减毒狂犬病活疫苗株）更好。综上所述，我们在这项研究中的数据表明，OX 40 L可以是一种新的和潜在的佐剂，以提高诱导保护性抗体反应后RABV免疫通过触发T细胞依赖性体液免疫反应，LBNSE-OX 40 L可以开发作为一种有效的和非致病性的疫苗的动物。
Rabies, caused by the rabies virus (RABV), remains a serious threat to public health in most countries. Development of a single-dose and efficacious rabies vaccine is the most important method to restrict rabies virus transmission. Costimulatory factor OX40-ligand (OX40L) plays a crucial role in the T cell-dependent humoral immune responses through T-B cell interaction. In this work, a recombinant RABV overexpressing mouse OX40L (LBNSE-OX40L) was constructed, and its effects on immunogenicity were evaluated in a mouse model. LBNSE-OX40L-immunized mice generated a larger number of T follicular helper (Tfh) cells, germinal center (GC) B cells, and plasma cells (PCs) than the parent virus LBNSE-immunized mice. Furthermore, LBNSE-OX40L induced significantly higher levels of virus-neutralizing antibodies (VNA) as early as seven days post immunization (dpi), which lasted for eight weeks, resulting in better protection for mice than LBNSE (a live-attenuated rabies vaccine strain). Taken together, our data in this study suggest that OX40L can be a novel and potential adjuvant to improve the induction of protective antibody responses post RABV immunization by triggering T cell-dependent humoral immune responses, and that LBNSE-OX40L can be developed as an efficacious and nonpathogenic vaccine for animals.