Liu Shiliang A, Stanfield Brent A, Chouljenko Vladimir N, Naidu Shan, Langohr Ingeborg, Del Piero Fabio, Ferracone Jacqueline, Roy Alma A, Kousoulas Konstantin G
Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana, USA.
Department of Clinical Studies and Pathology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, Pennsylvania, USA.
J Virol. 2017 May 26;91(12). doi: 10.1128/JVI.02445-16. Print 2017 Jun 15.
Vaccination remains the best option to combat equine herpesvirus 1 (EHV-1) infection, and several different strategies of vaccination have been investigated and developed over the past few decades. Herein, we report that the live-attenuated herpes simplex virus 1 (HSV-1) VC2 vaccine strain, which has been shown to be unable to enter into neurons and establish latency in mice, can be utilized as a vector for the heterologous expression of EHV-1 glycoprotein D (gD) and that the intramuscular immunization of mice results in strong antiviral humoral and cellular immune responses. The VC2-EHV-1-gD recombinant virus was constructed by inserting an EHV-1 gD expression cassette under the control of the cytomegalovirus immediate early promoter into the VC2 vector in place of the HSV-1 thymidine kinase (UL23) gene. The vaccines were introduced into mice through intramuscular injection. Vaccination with both the VC2-EHV-1-gD vaccine and the commercially available vaccine Vetera EHV 1/4 (Vetera; Boehringer Ingelheim Vetmedica) resulted in the production of neutralizing antibodies, the levels of which were significantly higher in comparison to those in VC2- and mock-vaccinated animals ( < 0.01 or < 0.001). Analysis of EHV-1-reactive IgG subtypes demonstrated that vaccination with the VC2-EHV-1-gD vaccine stimulated robust IgG1 and IgG2a antibodies after three vaccinations ( < 0.001). Interestingly, Vetera-vaccinated mice produced significantly higher levels of IgM than mice in the other groups before and after challenge ( < 0.01 or < 0.05). Vaccination with VC2-EHV-1-gD stimulated strong cellular immune responses, characterized by the upregulation of both interferon- and tumor necrosis factor-positive CD4 T cells and CD8 T cells. Overall, the data suggest that the HSV-1 VC2 vaccine strain may be used as a viral vector for the vaccination of horses as well as, potentially, for the vaccination of other economically important animals. A novel virus-vectored VC2-EHV-1-gD vaccine was constructed using the live-attenuated HSV-1 VC2 vaccine strain. This vaccine stimulated strong humoral and cellular immune responses in mice, suggesting that it could protect horses against EHV-1 infection.
接种疫苗仍然是对抗马疱疹病毒1型（EHV-1）感染的最佳选择，在过去几十年中，人们研究并开发了几种不同的疫苗接种策略。在此，我们报告称，减毒活单纯疱疹病毒1型（HSV-1）VC2疫苗株已被证明无法进入小鼠神经元并建立潜伏感染，可作为EHV-1糖蛋白D（gD）异源表达的载体，对小鼠进行肌肉注射免疫可引发强烈的抗病毒体液免疫和细胞免疫反应。通过将巨细胞病毒立即早期启动子控制下的EHV-1 gD表达盒插入VC2载体中取代HSV-1胸苷激酶（UL23）基因，构建了VC2-EHV-1-gD重组病毒。通过肌肉注射将疫苗接种到小鼠体内。接种VC2-EHV-1-gD疫苗和市售疫苗Vetera EHV 1/4（Vetera；勃林格殷格翰动物保健公司）均产生了中和抗体，与接种VC2疫苗和未接种疫苗的动物相比，中和抗体水平显著更高（<0.01或<0.001）。对EHV-1反应性IgG亚型的分析表明，接种VC2-EHV-1-gD疫苗三次后可刺激产生强大的IgG1和IgG2a抗体（<0.001）。有趣的是，在攻毒前后，接种Vetera疫苗的小鼠产生的IgM水平明显高于其他组的小鼠（<0.01或<0.
