Aggarwal Priya, Kumar Sanjeev, Vajpayee Madhu, Seth Pradeep
Department of Microbiology, All India Institute of Medical Sciences, New Delhi, India.
Viral Immunol. 2005;18(4):649-56. doi: 10.1089/vim.2005.18.649.
The human immunodeficiency virus (HIV) epidemic is probably the greatest scourge to affect mankind in the 20th century. Containment of the acquired immunodeficiency syndrome (AIDS) epidemic will require an effective vaccine. Of various vaccine approaches, immunization with DNA plasmids containing HIV-1 structural genes is the most popular approach. However, an important limitation of DNA immunization is that these responses are relatively weak and are often only transient in their nature. The use of immunologic adjuvants together with DNA vaccines is a promising way to enhance and to optimize DNA-derived immunity. Cytokines have been widely used to enhance the immune responses of DNA vaccines. In the present investigation, we studied the in vivo immunomodulation of HIV-1 Indian subtype C plasmid construct (pJWSK3, encoding envgp120 gene) by plasmid-based murine IL-2/Ig construct. Subcloning of mIL-2/Ig gene from pVRCmIL-2/Ig construct into pJW4304 vector was done followed by its in vitro expression study on the COS-7 cell line. Co-immunization of the recombinant HIV-1 env-gp120 construct with the IL-2/Ig construct in the female Balb/c mice by the intramuscular route resulted in induction of significantly higher levels of both HIV-1-specific antibody response and cell mediated immune response than by DNA plasmid construct alone (p < 0.001 and p < 0.05, respectively). The induced HIV-1-specific murine IFN-gamma response was robust, broad based, and seen even at the end of 6 months after immunization. Taken together these results indicate that the strategy of using IL-2/Ig plasmid can be highly effective when used along with recombinant DNA constructs and serve as the potential tool for the development of more rationally designed vaccines against HIV-1.
人类免疫缺陷病毒(HIV)流行可能是20世纪影响人类的最大灾难。控制获得性免疫缺陷综合征(AIDS)流行需要一种有效的疫苗。在各种疫苗方法中,用含有HIV-1结构基因的DNA质粒进行免疫是最受欢迎的方法。然而,DNA免疫的一个重要局限性是这些反应相对较弱,而且本质上往往只是短暂的。将免疫佐剂与DNA疫苗一起使用是增强和优化DNA衍生免疫的一种有前途的方法。细胞因子已被广泛用于增强DNA疫苗的免疫反应。在本研究中,我们研究了基于质粒的小鼠IL-2/Ig构建体对HIV-1印度C亚型质粒构建体(pJWSK3,编码envgp120基因)的体内免疫调节作用。将mIL-2/Ig基因从pVRCmIL-2/Ig构建体亚克隆到pJW4304载体中,随后在COS-7细胞系上进行体外表达研究。通过肌肉内途径将重组HIV-1 env-gp120构建体与IL-2/Ig构建体共同免疫雌性Balb/c小鼠,与单独使用DNA质粒构建体相比,导致诱导出显著更高水平的HIV-1特异性抗体反应和细胞介导的免疫反应(分别为p < 0.001和p < 0.05)。诱导的HIV-1特异性小鼠IFN-γ反应强烈、广泛,甚至在免疫后6个月结束时仍可见。综上所述,这些结果表明,IL-2/Ig质粒与重组DNA构建体一起使用时可能非常有效,并可作为开发更合理设计的抗HIV-1疫苗的潜在工具。