Instituto de Virología-IVIT (INTA-CONICET), Buenos Aires, Argentina.
Universidad Nacional de Rio Negro, Sede Atlántica, Viedma, Río Negro, Argentina.
Viral Immunol. 2021 Mar;34(2):68-78. doi: 10.1089/vim.2020.0082. Epub 2020 Nov 3.
Bovine herpesvirus-1 (BoHV-1) uses many mechanisms to elude the immune system; one of them is spreading intracellularly, even in the presence of specific antiviral antibodies. Cytotoxic T lymphocytes (CTLs) are necessary to eliminate the virus. The main preventive strategy is vaccination based on inactivated virus. These vaccines are poor inducers of cellular immune responses, and complicate serological diagnosis and determination of the real prevalence of infection. DNA vaccines are a good option because of the capacity of Differentiating Infected from Vaccinated Animals-(DIVA vaccine)-and may be the best way to induce cytotoxic responses. Although this type of vaccines leads to only weak "" expression and poor immune responses, incorporation of molecular and/or chemical adjuvants can improve the latter, both in magnitude and in direction. In this study, we have investigated the specific immune responses elicited in mice by DNA vaccines based on the BoHV-1 glycoprotein D (pCIgD) with and without two different adjuvants: a plasmid encoding for murine (pCD40L) or Montanide™ 1113101PR (101). Mice vaccinated with pCIgDCD40L, pCIgD101, and pCIgDCD40L101 developed significantly higher specific antibody titers against BoHV-1 than the pCIgD group ( < 0.01). The animals vaccinated with pCgDpCD40L101 raised significantly higher levels of IgG2a and IgG2b ( < 0.01 and < 0.001, respectively) than mice vaccinated with pCIgD alone. On the contrary, when the activity of CTL against cells infected with BoHV-1 was measured, the vaccine pCgDpCD40L101 induced significantly higher levels of cytotoxicity activity ( < 0.001) than pCIgD alone. A significant increase in the CD4 populations in the group receiving pCIgDCD40L101 in comparison with the pCIgD group was observed and, also, interferon gamma, interleukin (IL)-6, and IL-17A levels were higher. Considering the results obtained from this study for humoral and cellular responses in mice, the inclusion of pCD40L and 101 as adjuvants in a BoHV-1 DNA vaccine for cattle is highly recommendable.
牛疱疹病毒 1（BoHV-1）利用多种机制逃避免疫系统；其中之一是在存在特异性抗病毒抗体的情况下进行细胞内传播。细胞毒性 T 淋巴细胞（CTL）是消除病毒所必需的。主要的预防策略是基于灭活病毒的疫苗接种。这些疫苗对细胞免疫反应的诱导作用较差，并且使血清学诊断和感染的实际流行率的确定复杂化。DNA 疫苗是一个很好的选择，因为它具有区分感染动物和接种疫苗动物的能力（DIVA 疫苗），并且可能是诱导细胞毒性反应的最佳方法。尽管这种类型的疫苗仅导致较弱的“表达”和较差的免疫反应，但掺入分子和/或化学佐剂可以改善其反应，无论是在幅度还是在方向上。在这项研究中，我们研究了基于 BoHV-1 糖蛋白 D（pCIgD）的 DNA 疫苗在有和没有两种不同佐剂的情况下在小鼠中引起的特异性免疫应答：一种编码小鼠 （pCD40L）的质粒或 Montanide™1113101PR（101）。与 pCIgD 组相比，接种 pCIgDCD40L、pCIgD101 和 pCIgDCD40L101 的小鼠对 BoHV-1 的特异性抗体滴度显著升高（<0.01）。与单独接种 pCgD 相比，接种 pCgDpCD40L101 的小鼠 IgG2a 和 IgG2b 的水平显著升高（<0.01 和 <0.001）。相反，当测量针对 BoHV-1 感染细胞的 CTL 活性时，与单独接种 pCIgD 相比，pCgDpCD40L101 诱导的细胞毒性活性显著升高（<0.001）。与 pCIgD 组相比，接受 pCIgDCD40L101 的小鼠 CD4 群体显著增加，并且干扰素γ、白细胞介素（IL）-6 和 IL-17A 水平也更高。考虑到本研究中在小鼠中获得的体液和细胞反应的结果，强烈建议在 BoHV-1 DNA 疫苗中加入 pCD40L 和 101 作为佐剂用于牛。
