Liu Shiliang A, Haque Muzammel, Stanfield Brent, Andrews Frank M, Roy Alma A, Kousoulas Konstantin G
Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, USA.
Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, USA.
Vet Microbiol. 2017 Jan;198:51-58. doi: 10.1016/j.vetmic.2016.12.008. Epub 2016 Dec 8.
West Nile Virus (WNV) is endemic in the US and causes severe neurologic disease in horses since its introduction in 1999. There is no effective pharmaceutical treatment for WNV infection rendering vaccination as the only approach to prevention and control of disease. The purpose of this study was to evaluate a recombinant vaccine containing domain III (DIII) of the WNV envelope glycoprotein with and without a natural adjuvant equine (CD40L) in producing virus neutralizing antibodies in horses. Serum IgG1 concentration in the groups of horses vaccinated with the DIII-CD40L+TiterMax and DIII-CD40L proteins were significantly increased (p<0.05) after the second booster vaccination compared to other groups. Serum IgG4 and IgG7, IgG3 and IgG5 concentrations were not significantly increased among all groups. Western blot results showed that animals immunized with the DIII-CD40L protein (with or without TiterMax) exhibited the highest specific anti-DIII antibody activities after vaccinations. Moreover, animals immunized with the DIII-CD40L protein (with or without TiterMax) exhibited significantly stronger neutralization activity (p<0.05) compared to other groups starting at week eight. The DIII-CD40L protein (with or without TiterMax) stimulated more CD8T cells, but not CD4T cells in equine PMBCs. The results demonstrated that vaccination with recombinant WNV E DIII-CD40L protein induced superior humoral and cellular immune response in healthy horses that may be protective against WNV-associated disease in infected animals. CD40L could be utilized as a non-toxic, alternative adjuvant to boost the immunogenicity of subunit vaccines in horses.
西尼罗河病毒（WNV）在美国呈地方性流行，自1999年传入以来，可导致马匹发生严重的神经系统疾病。目前尚无针对WNV感染的有效药物治疗方法，因此疫苗接种是预防和控制该疾病的唯一途径。本研究的目的是评估一种含有WNV包膜糖蛋白结构域III（DIII）的重组疫苗，该疫苗添加或不添加天然佐剂马CD40L，在马匹中产生病毒中和抗体的效果。与其他组相比，接种DIII-CD40L+TiterMax和DIII-CD40L蛋白的马匹组在第二次加强免疫后血清IgG1浓度显著升高（p<0.05）。所有组中血清IgG4和IgG7、IgG3和IgG5浓度均未显著升高。蛋白质印迹结果显示，接种DIII-CD40L蛋白（添加或不添加TiterMax）的动物在接种疫苗后表现出最高的特异性抗DIII抗体活性。此外，从第8周开始，与其他组相比，接种DIII-CD40L蛋白（添加或不添加TiterMax）的动物表现出显著更强的中和活性（p<0.05）。DIII-CD40L蛋白（添加或不添加TiterMax）刺激马外周血单核细胞中的CD8T细胞增多，但不刺激CD4T细胞。结果表明，接种重组WNV E DIII-CD40L蛋白可在健康马匹中诱导出卓越的体液免疫和细胞免疫反应，可能对感染动物的WNV相关疾病具有保护作用。CD40L可作为一种无毒的替代佐剂，增强马匹亚单位疫苗的免疫原性。
