Kumar Sanjeev, Aggarwal Priya, Vajpayee Madhu, Pandey R M, Seth Pradeep
Department of Microbiology, All India Institute of Medical Sciences, New Delhi 110029, India.
Vaccine. 2006 Mar 24;24(14):2585-93. doi: 10.1016/j.vaccine.2005.12.032. Epub 2006 Jan 4.
Development of a vaccine against human immunodeficiency virus type-1 (HIV-1) is the mainstay for controlling the AIDS pandemic. An ideal HIV vaccine should induce neutralizing antibodies, CD4+ helper T cells, and CD8+ cytotoxic T cells. While the induction of broadly neutralizing antibodies remains a highly challenging goal, there are a number of technologies capable of inducing potent cell-mediated responses in animal models, which are now starting to be tested in humans. Naked DNA immunization is one of them. The present study focuses on the stimulation cell-mediated and humoral immune responses by recombinant DNA-MVA vaccines, the areas where this technology might assist either alone or as a part of more complex vaccine formulations in the HIV vaccine development. Candidate recombinant DNA-MVA vaccine formulations expressing the human immunodeficiency virus-1 env and gagprotease genes from HIV-1 Indian subtype C were constructed and characterized. A high level of expression of the respective recombinant MVA (rMVA) constructs was demonstrated in BHK-21 cells followed by the robust humoral as well as cell mediated immune (CMI) responses in terms of magnitude and breadth. The response to a single inoculation of the rDNA vaccine was boosted efficiently by rMVA in BALB/c mice. This is the first reported candidate HIV-1 DNA/MVA vaccine employing the Indian subtype C sequences and constitutes a part of a vaccine scheduled to enter a preclinical non-human primate evaluation in India.
开发针对人类免疫缺陷病毒1型(HIV-1)的疫苗是控制艾滋病大流行的主要手段。理想的HIV疫苗应诱导中和抗体、CD4+辅助性T细胞和CD8+细胞毒性T细胞。虽然诱导广泛中和抗体仍然是一个极具挑战性的目标,但有多种技术能够在动物模型中诱导强大的细胞介导反应,目前这些技术已开始在人体中进行测试。裸DNA免疫就是其中之一。本研究聚焦于重组DNA-MVA疫苗对细胞介导免疫和体液免疫反应的刺激作用,以及该技术在HIV疫苗开发中单独或作为更复杂疫苗配方的一部分可能发挥作用的领域。构建并表征了表达来自HIV-1印度C亚型的人类免疫缺陷病毒-1 env和gag蛋白酶基因的候选重组DNA-MVA疫苗配方。在BHK-21细胞中证实了各自重组MVA(rMVA)构建体的高水平表达,随后在强度和广度方面引发了强大的体液免疫以及细胞介导免疫(CMI)反应。在BALB/c小鼠中,rMVA有效地增强了对单次接种rDNA疫苗的反应。这是首次报道的采用印度C亚型序列的候选HIV-1 DNA/MVA疫苗,并且是计划在印度进入临床前非人灵长类动物评估的疫苗的一部分。