Gönczöl E, Berensci K, Pincus S, Endresz V, Méric C, Paoletti E, Plotkin S A
Wistar Institute of Anatomy and Biology, Philadelphia, PA 19104, USA.
Vaccine. 1995 Aug;13(12):1080-5. doi: 10.1016/0264-410x(95)00048-6.
Successful vaccination against the human cytomegalovirus (HCMV) requires induction of both neutralizing antibody and cytotoxic T lymphocyte (CTL) responses. The HCMV glycoprotein B (gB, UL55) would be one of the most important immunogens to induce neutralizing antibodies. We tested the immunogenicity of an ALVAC (canarypox)-HCMV-gB (ALVAC-gB) recombinant in mice and guinea pigs in order to provide preclinical data for a phase I clinical trial of a HCMV vaccine candidate. ALVAC is an attenuated vaccine strain of canarypox virus which replicates productively in avian species but abortively in mammalian cells. The ALVAC-gB recombinant inoculated subcutaneously in mice and intramuscularly in guinea pigs induced HCMV-specific neutralizing antibodies and gB-specific CTL responses. Ultraviolet irradiation of the ALVAC-gB recombinant before immunization diminished CTL responses, indicating that intracellular expression and processing of gB-protein were necessary for CTL induction. Prior immunity to vaccinia virus did not decrease immunogenicity of the ALVAC-gB recombinant in mice. Thus, despite its host range restriction, ALVAC-gB is potentially capable of inducing both humoral and cell-mediated immune responses to HCMV in both vaccinia-immune and non-immune individuals.
成功接种人巨细胞病毒（HCMV）疫苗需要诱导中和抗体和细胞毒性T淋巴细胞（CTL）反应。HCMV糖蛋白B（gB，UL55）可能是诱导中和抗体的最重要免疫原之一。我们在小鼠和豚鼠中测试了一种ALVAC（金丝雀痘病毒）-HCMV-gB（ALVAC-gB）重组体的免疫原性，以便为一种HCMV候选疫苗的I期临床试验提供临床前数据。ALVAC是一种金丝雀痘病毒的减毒疫苗株，它能在禽类中有效复制，但在哺乳动物细胞中则不能。在小鼠中皮下接种以及在豚鼠中肌肉接种ALVAC-gB重组体可诱导HCMV特异性中和抗体和gB特异性CTL反应。免疫前对ALVAC-gB重组体进行紫外线照射会减弱CTL反应，这表明gB蛋白的细胞内表达和加工对于CTL诱导是必要的。先前对痘苗病毒的免疫并不会降低ALVAC-gB重组体在小鼠中的免疫原性。因此，尽管其宿主范围有限，但ALVAC-gB在对痘苗病毒免疫和未免疫的个体中都有可能诱导针对HCMV的体液免疫和细胞介导免疫反应。
