Huang Y, Babiuk L A, van Drunen Littel-van den Hurk S
Vaccine and Infectious Disease Organization, University of Saskatchewan, 120 Veterinary Road, Saskatoon, Saskatchewan, Canada S7N 5E3.
J Gen Virol. 2005 Apr;86(Pt 4):887-898. doi: 10.1099/vir.0.80533-0.
Virus-specific cytotoxic T lymphocytes (CTLs) are considered to be important in protection against and recovery from viral infections. In this study, several approaches to induce cytotoxicity against bovine herpesvirus 1 (BHV-1) were evaluated. Vaccination of C57BL/6 mice with BHV-1 induced a strong humoral, but no CTL, response, which may be due to downregulation of major histocompatibility complex class I molecules. In contrast, vaccinia virus expressing glycoprotein B (gB) elicited a weaker antibody response, but strong cytotoxicity, in mice. As an approach to inducing both strong humoral and cellular immune responses, a plasmid vector was then used to express gB. Both antibody and CTL responses were induced by the plasmid encoding gB in C57BL/6 and C3H mice, regardless of the type of vector backbone. This demonstrated that DNA immunization induces a broad-based immune response to BHV-1 gB. Interestingly, removal of the membrane anchor, which resulted in secretion of gB from transfected cells, did not result in reduced cytotoxicity. Here, it is shown that, compared with the cell-associated counterpart, plasmid-encoded secreted protein may induce enhanced immune responses in cattle. Therefore, calves were immunized intradermally with pMASIAtgB, a plasmid encoding the secreted form of gB (tgB), using a needle-free injection system. This demonstrated that pMASIAtgB elicited both humoral responses and activated gamma interferon-secreting CD8+ CTLs, suggesting that a DNA vaccine expressing tgB induces a CTL response in the natural host of BHV-1.
病毒特异性细胞毒性T淋巴细胞(CTLs)被认为在预防病毒感染和从病毒感染中恢复方面发挥着重要作用。在本研究中,评估了几种诱导针对牛疱疹病毒1型(BHV-1)细胞毒性的方法。用BHV-1对C57BL/6小鼠进行疫苗接种可诱导强烈的体液免疫反应,但无CTL反应,这可能是由于主要组织相容性复合体I类分子的下调所致。相比之下,表达糖蛋白B(gB)的痘苗病毒在小鼠中引发较弱的抗体反应,但具有较强的细胞毒性。作为诱导强烈体液免疫和细胞免疫反应的一种方法,随后使用质粒载体来表达gB。无论载体骨架类型如何,编码gB的质粒在C57BL/6和C3H小鼠中均诱导了抗体和CTL反应。这表明DNA免疫诱导了对BHV-1 gB的广泛免疫反应。有趣的是,去除膜锚定序列(这导致gB从转染细胞中分泌)并没有导致细胞毒性降低。在此表明,与细胞相关的对应物相比,质粒编码的分泌蛋白可能在牛中诱导增强的免疫反应。因此,使用无针注射系统对犊牛进行皮内免疫接种pMASIAtgB,这是一种编码gB分泌形式(tgB)的质粒。这表明pMASIAtgB引发了体液免疫反应并激活了分泌γ干扰素的CD8 + CTL,表明表达tgB的DNA疫苗在BHV-1的天然宿主中诱导了CTL反应。