Gupta Soumi, Leutenegger Christian M, Dean Gregg A, Steckbeck Jonathan D, Cole Kelly Stefano, Sparger Ellen E
Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, CA 95616, USA.
J Virol. 2007 Jan;81(2):465-73. doi: 10.1128/JVI.00815-06. Epub 2006 Nov 1.
A feline immunodeficiency virus (FIV) provirus with a vif gene deletion (FIVDelta vifATGgamma) that coexpresses feline gamma interferon (IFN-gamma) was tested as a proviral DNA vaccine to extend previous studies showing efficacy with an FIV-pPPRDelta vif DNA vaccine. Cats were vaccinated with either FIVDelta vifATGgamma or FIV-pPPRDelta vif proviral plasmid DNA or with both FIV-pPPRDelta vif DNA and a feline IFN-gamma expression plasmid (pCDNA-IFNgamma). A higher frequency of FIV-specific T-cell proliferation responses was observed in cats immunized with either FIVDelta vifATGgamma or FIV-pPPRDelta vif plus pCDNA-IFNgamma, while virus-specific cytotoxic-T-lymphocyte responses were comparable between vaccine groups. Antiviral antibodies were not observed postvaccination. Virus-specific cellular and humoral responses were similar between vaccine groups after challenge with a biological FIV isolate (FIV-PPR) at 13 weeks postimmunization. All vaccinated and unvaccinated cats were infected after FIV-PPR challenge and exhibited similar plasma virus loads. Accordingly, inclusion of plasmids containing IFN-gamma did not enhance the efficacy of FIV-pPPRDelta vif DNA immunization. Interestingly, the lack of protection associated with FIV-pPPRDelta vif DNA immunization contrasted with findings from a previous study and suggested that multiple factors, including timing of FIV-pPPRDelta vif inoculations and challenge, as well as route of challenge virus delivery, may significantly impact vaccine efficacy.
一种携带vif基因缺失的猫免疫缺陷病毒(FIV)前病毒(FIVDelta vifATGgamma),其共表达猫γ干扰素(IFN-γ),作为一种前病毒DNA疫苗进行了测试,以扩展先前关于FIV-pPPRDelta vif DNA疫苗有效性的研究。给猫接种FIVDelta vifATGgamma或FIV-pPPRDelta vif前病毒质粒DNA,或同时接种FIV-pPPRDelta vif DNA和猫IFN-γ表达质粒(pCDNA-IFNgamma)。在用FIVDelta vifATGgamma或FIV-pPPRDelta vif加pCDNA-IFNgamma免疫的猫中,观察到更高频率的FIV特异性T细胞增殖反应,而疫苗组之间的病毒特异性细胞毒性T淋巴细胞反应相当。接种疫苗后未观察到抗病毒抗体。在免疫后13周用生物FIV分离株(FIV-PPR)攻击后,疫苗组之间的病毒特异性细胞和体液反应相似。所有接种疫苗和未接种疫苗的猫在FIV-PPR攻击后均被感染,且血浆病毒载量相似。因此,包含IFN-γ的质粒并未增强FIV-pPPRDelta vif DNA免疫的效果。有趣的是,FIV-pPPRDelta vif DNA免疫缺乏保护作用,这与先前一项研究的结果形成对比,表明包括FIV-pPPRDelta vif接种和攻击的时间以及攻击病毒的递送途径等多种因素可能会显著影响疫苗效果。