Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Annu Rev Immunol. 2010;28:413-44. doi: 10.1146/annurev-immunol-030409-101256.
Licensed vaccines against viral diseases generate antibodies that neutralize the infecting virus and protect against infection or disease. Similarly, an effective vaccine against HIV-1 will likely need to induce antibodies that prevent initial infection of host cells or that limit early events of viral dissemination. Such antibodies must target the surface envelope glycoproteins of HIV-1, which are highly variable in sequence and structure. The first subunit vaccines to enter clinical trails were safe and immunogenic but unable to elicit antibodies that neutralized most circulating strains of HIV-1. However, potent virus neutralizing antibodies (NAbs) can develop during the course of HIV-1 infection, and this is the type of antibody response that researchers seek to generate with a vaccine. Thus, current vaccine design efforts have focused on a more detailed understanding of these broadly neutralizing antibodies and their epitopes to inform the design of improved vaccines.
针对病毒性疾病的许可疫苗会产生能够中和感染病毒的抗体,从而预防感染或疾病。同样,针对 HIV-1 的有效疫苗可能需要诱导出能够预防宿主细胞初始感染或限制病毒传播早期事件的抗体。此类抗体必须针对 HIV-1 的表面包膜糖蛋白,该蛋白在序列和结构上高度可变。首先进入临床试验的亚单位疫苗是安全且具有免疫原性的,但无法诱发出能够中和大多数循环 HIV-1 毒株的抗体。然而,在 HIV-1 感染过程中可以产生有效的病毒中和抗体(NAb),这是研究人员试图通过疫苗产生的抗体反应类型。因此,目前的疫苗设计工作侧重于更详细地了解这些广泛中和抗体及其表位,以指导改进疫苗的设计。