Human Vaccine Institute and Department of Medicine, Duke University Medical Center, Durham, NC 27710, United States.
Human Vaccine Institute and Department of Medicine, Duke University Medical Center, Durham, NC 27710, United States.
J Virol Methods. 2017 Nov;249:85-93. doi: 10.1016/j.jviromet.2017.08.012. Epub 2017 Aug 31.
Development of a HIV-1 vaccine is a major global priority. The yellow fever virus (YFV) attenuated vaccine 17D is among the most effective of currently used vaccines. However, the stability of the YFV17D vector when carrying non-flavivirus genes has been problematic. We have constructed and expressed HIV-1 Env in YFV17D with either single transmembrane (STM) or double transmembrane (DTM) YFV E protein domains for the development of anti-HIV antibodies. Here we describe modifications of the YFV17D vector such that HIV-1 Env gp120 is expressed in up to 5 passages in Vero cells. Immunization with recombinant YFV17D vector prime followed by HIV-1 CH505 TF gp120 protein boosts were able to induce neutralizing antibodies for a HIV-1 tier 1 isolate in mice. This modified YFV vector may be a starting point for constructing HIV-1 vaccine candidate priming vectors.
开发 HIV-1 疫苗是全球的主要重点。减毒黄热病毒(YFV)17D 疫苗是目前使用的最有效的疫苗之一。然而,当携带非黄病毒基因时,YFV17D 载体的稳定性一直存在问题。我们构建并在 YFV17D 中表达了 HIV-1Env,其中包含单跨膜(STM)或双跨膜(DTM)YFV E 蛋白结构域,用于开发抗 HIV 抗体。在这里,我们描述了对 YFV17D 载体的修饰,使得 HIV-1Env gp120 可以在 Vero 细胞中表达多达 5 代。用重组 YFV17D 载体进行免疫接种,然后用 HIV-1CH505TF gp120 蛋白进行加强免疫,能够在小鼠中诱导针对 HIV-1 一级分离株的中和抗体。这种改良的 YFV 载体可能是构建 HIV-1 疫苗候选物起始载体的起点。