Lu Shan
Laboratory of Nucleic Acid Vaccines, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Springer Semin Immunopathol. 2006 Nov;28(3):255-65. doi: 10.1007/s00281-006-0028-1. Epub 2006 Sep 21.
A major challenge in developing an HIV vaccine is to identify immunogens and delivery methods that will elicit balanced humoral and cell mediate immunities against primary isolates of HIV with diverse sequence variations. Since the discovery of using protein coding nucleic acids (mainly DNA but also possible RNA) as a means of immunization in the early 1990s, there has been rapid progress in the creative use of this novel approach for the development of HIV vaccines. Although the initial impetus of using DNA immunization was for the induction of strong cell-mediated immunity, recent studies have greatly expanded our understanding on the potential role of DNA immunization to elicit improved quality of antibody responses. This function is particularly important to the development of HIV vaccines due to the inability of almost every previous attempt to develop broadly reactive neutralizing antibodies against primary HIV-1 isolates. Similar to the efforts of developing cell mediated immunity by using a DNA prime plus viral vector boost approach, the best antibody responses with DNA immunization were achieved when a protein boost component was included as part of the immunization schedule. Current experience has suggested that a combination DNA plus protein vaccination strategy is able to utilize the benefits of DNA and protein vaccines to effectively induce both cell-mediated immunity and antibody responses against invading organisms.
开发HIV疫苗面临的一个主要挑战是确定免疫原和递送方法,以引发针对具有不同序列变异的HIV原始分离株的平衡的体液免疫和细胞介导免疫。自20世纪90年代初发现使用蛋白质编码核酸(主要是DNA,但也可能是RNA)作为免疫手段以来,在创造性地利用这种新方法开发HIV疫苗方面取得了迅速进展。尽管使用DNA免疫的最初动力是诱导强大的细胞介导免疫,但最近的研究极大地扩展了我们对DNA免疫在引发更高质量抗体反应方面潜在作用的理解。由于几乎以前每次尝试开发针对HIV-1原始分离株的广泛反应性中和抗体均未成功,因此该功能对HIV疫苗的开发尤为重要。与使用DNA初免加病毒载体加强方法开发细胞介导免疫的努力类似,当将蛋白质加强成分作为免疫方案的一部分时,DNA免疫可实现最佳抗体反应。目前的经验表明,DNA与蛋白质联合疫苗接种策略能够利用DNA和蛋白质疫苗的优势,有效诱导针对入侵生物体的细胞介导免疫和抗体反应。