van Gils Marit J, Schuitemaker Hanneke
Department Experimental Immunology, Academic Medical Center, Meibergdreef 9, Room M01-120, 1105 AZ Amsterdam, The Netherlands.
Curr HIV Res. 2010 Dec;8(8):579-86. doi: 10.2174/157016210794088254.
The correlates of protection against HIV-1 infection or disease progression are still unknown which causes an immense challenge for HIV-1 vaccine design. Existing effective vaccines against other viruses generate antibodies that either block the initial infection or contribute to the eradication of the virus before it can cause disease. For HIV-1, a protective vaccine capable of eliciting protective neutralizing antibodies does not exist and the difficulties for the generation of such a vaccine are multiple. Conserved elements on the viral envelope glycoprotein, the target of HIV-specific neutralizing antibodies, seem to be poorly immunogenic and attempts to generate an immunogen that can elicit broadly reactive neutralizing antibodies have remained largely without success. In addition, the envelope of HIV-1 is highly variable with respect to amino acid sequence, length of the variable loops, and glycosylation pattern. To cope with the high sequence variation, vaccine-elicited clade-specific neutralizing antibodies have been suggested as an attractive alternative and recent studies have revealed some evidence for the existence of HIV-1 clade-specific humoral immune responses. Here, we will review these recent findings and hypothesize on the nature of clade-specific humoral immunity also in light of their relevance for HIV-1 vaccine development.
针对HIV-1感染或疾病进展的保护性相关因素仍不清楚，这给HIV-1疫苗设计带来了巨大挑战。现有的针对其他病毒的有效疫苗会产生抗体，这些抗体要么阻止初始感染，要么在病毒引发疾病之前协助清除病毒。对于HIV-1而言，不存在能够引发保护性中和抗体的保护性疫苗，并且研发此类疫苗存在诸多困难。HIV特异性中和抗体的靶标——病毒包膜糖蛋白上的保守元件，似乎免疫原性很差，试图生成能引发广泛反应性中和抗体的免疫原在很大程度上仍未成功。此外，HIV-1的包膜在氨基酸序列、可变环长度和糖基化模式方面高度可变。为应对高度的序列变异，有人提出疫苗引发的特定分支中和抗体是一种有吸引力的替代方案，最近的研究揭示了一些证据，表明存在HIV-1特定分支的体液免疫反应。在此，我们将回顾这些最新发现，并根据它们与HIV-1疫苗开发的相关性，对特定分支体液免疫的性质进行推测。
