Chege Gerald K, Thomas Robin, Shephard Enid G, Meyers Ann, Bourn William, Williamson Carolyn, Maclean James, Gray Clive M, Rybicki Edward P, Williamson Anna-Lise
Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory, Cape Town, South Africa.
Vaccine. 2009 Jul 30;27(35):4857-66. doi: 10.1016/j.vaccine.2009.05.064. Epub 2009 Jun 9.
Mycobacterium bovis BCG is considered an attractive live bacterial vaccine vector. In this study, we investigated the immune response of baboons to a primary vaccination with recombinant BCG (rBCG) constructs expressing the gag gene from a South African HIV-1 subtype C isolate, and a boost with HIV-1 subtype C Pr55(gag) virus-like particles (Gag VLPs). Using an interferon enzyme-linked immunospot assay, we show that although these rBCG induced only a weak or an undetectable HIV-1 Gag-specific response on their own, they efficiently primed for a Gag VLP boost, which strengthened and broadened the immune responses. These responses were predominantly CD8+ T cell-mediated and recognised similar epitopes as those targeted by humans with early HIV-1 subtype C infection. In addition, a Gag-specific humoral response was elicited. These data support the development of HIV-1 vaccines based on rBCG and Pr55(gag) VLPs.
牛分枝杆菌卡介苗(Mycobacterium bovis BCG)被认为是一种有吸引力的活细菌疫苗载体。在本研究中,我们调查了狒狒对表达来自南非HIV-1 C亚型分离株gag基因的重组卡介苗(rBCG)构建体初次接种以及用HIV-1 C亚型Pr55(gag)病毒样颗粒(Gag VLPs)加强免疫后的免疫反应。使用干扰素酶联免疫斑点试验,我们发现尽管这些rBCG单独诱导的HIV-1 Gag特异性反应微弱或无法检测到,但它们能有效地启动对Gag VLPs的加强免疫,从而增强并拓宽了免疫反应。这些反应主要由CD8 + T细胞介导,并且识别的表位与早期HIV-1 C亚型感染的人类所靶向的表位相似。此外,还引发了Gag特异性体液反应。这些数据支持基于rBCG和Pr55(gag)VLPs的HIV-1疫苗的开发。