Instituto de Virología e Innovaciones Tecnológicas (IVIT, INTA-CONICET), Hurlingham, Argentina.
Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina.
Transbound Emerg Dis. 2021 Mar;68(2):587-597. doi: 10.1111/tbed.13718. Epub 2020 Jul 22.
New technologies in the field of vaccinology arise as a necessity for the treatment and control of many diseases. Whole virus inactivated vaccines and modified live virus ones used against Bovine Herpesvirus-1 (BoHV-1) infection have several disadvantages. Previous works on DNA vaccines against BoHV-1 have demonstrated the capability to induce humoral and cellular immune responses. Nevertheless, 'naked' DNA induces low immunogenic response. Thus, loading of antigen encoding DNA sequences in liposomal formulations targeting dendritic cell receptors could be a promising strategy to better activate these antigen-presenting cells (APC). In this work, a DNA-based vaccine encoding the truncated version of BoHV-1 glycoprotein D (pCIgD) was evaluated alone and encapsulated in a liposomal formulation containing LPS and decorated with MANα1-2MAN-PEG-DOPE (pCIgD-Man-L). The vaccinations were performed in mice and bovines. The results showed that the use of pCIgD-Man-L enhanced the immune response in both animal models. For humoral immunity, significant differences were achieved when total antibody titres and isotypes were assayed in sera. Regarding cellular immunity, a significant increase in the proliferative response against BoHV-1 was detected in animals vaccinated with pCIgD-Man-L when compared to the response induced in animals vaccinated with pCIgD. In addition, upregulation of CD40 molecules on the surface of bovine dendritic cells (DCs) was observed when cells were stimulated and activated with the vaccine formulations. When viral challenge was performed, bovines vaccinated with MANα1-2MAN-PEG-DOPE elicited better protection which was evidenced by a lower viral excretion. These results demonstrate that the dendritic cell targeting using MANα1-2MAN decorated liposomes can boost the immunogenicity resulting in a long-lasting immunity. Liposomes decorated with MANα1-2MAN-PEG-DOPE were tested for the first time as a DNA vaccine nanovehicle in cattle as a preventive treatment against BoHV-1. These results open new perspectives for the design of vaccines for the control of bovine rhinotracheitis.
新型疫苗技术是治疗和控制多种疾病的必然需求。针对牛疱疹病毒 1 型（BoHV-1）感染而使用的全病毒灭活疫苗和减毒活疫苗存在一些缺点。针对 BoHV-1 的 DNA 疫苗的前期研究已经证明了其诱导体液和细胞免疫应答的能力。然而，“裸”DNA 会引起低免疫原性反应。因此，将编码抗原的 DNA 序列加载到针对树突状细胞受体的脂质体制剂中可能是一种很有前途的策略，可以更好地激活这些抗原呈递细胞（APC）。在这项工作中，我们评估了编码 BoHV-1 糖蛋白 D 截断版本的 DNA 疫苗（pCIgD）单独使用和封装在含有 LPS 的脂质体制剂中并修饰有 MANα1-2MAN-PEG-DOPE（pCIgD-Man-L）的效果。在小鼠和牛中进行了疫苗接种。结果表明，在两种动物模型中，使用 pCIgD-Man-L 增强了免疫反应。就体液免疫而言，当在血清中检测总抗体滴度和同种型时，差异具有统计学意义。关于细胞免疫，与接种 pCIgD 的动物相比，接种 pCIgD-Man-L 的动物的针对 BoHV-1 的增殖反应显著增加。此外，当用疫苗制剂刺激和激活牛树突状细胞（DC）时，观察到细胞表面 CD40 分子的上调。当进行病毒攻击时，用 MANα1-2MAN 修饰的脂质体进行靶向树突状细胞的免疫接种可以产生更好的保护作用，这体现在病毒排出量较低。这些结果表明，使用 MANα1-2MAN 修饰的脂质体靶向树突状细胞可以增强免疫原性，从而产生持久的免疫力。MANα1-2MAN-PEG-DOPE 修饰的脂质体首次作为 DNA 疫苗纳米载体在牛中进行了测试，作为预防 BoHV-1 的治疗方法。这些结果为设计控制牛鼻气管炎的疫苗开辟了新的前景。
