Wang Lai-Xi
Institute of Human Virology, University of Maryland Biotechnology Institute, University of Maryland, 725 W. Lombard Street, Baltimore, MD 21201, USA.
Curr Pharm Des. 2003;9(22):1771-87. doi: 10.2174/1381612033454432.
The worldwide epidemic of HIV/AIDS urges the development of an effective vaccine. With the identification of HIV as the cause of AIDS about two decades ago, it was once expected that a preventive vaccine would follow closely behind. But the early promise of HIV envelope gp120 as a preventive vaccine was not fulfilled. Broadly neutralizing antibodies and HIV-specific cytotoxic T lymphocytes (CTL) are two immune effectors that an effective HIV vaccine may have to elicit. Experiments in animal models have proved that sufficient levels of neutralizing antibodies can clean up the virus and protect the animals from viral challenge. Therefore, the induction of a broadly neutralizing antibody response remains a principal goal in HIV vaccine development. To achieve persistent infection, HIV has evolved elegant strategies to evade host immune surveillance. These include envelope oligomerization, rapid mutation, heavy glycosylation, and conformational changes. Each level of the HIV's defenses provides an additional dimension of complexity that has to be taken into account in order to come up with a vaccine conferring strong and long lasting immunity. Important progresses have been made in recent years in understanding the structure of HIV envelopes and the molecular mechanism of HIV evasion to the immune system. This in turn has greatly facilitated a rational design of immunogens capable of eliciting broadly neutralizing antibodies against HIV. The present review provides an overview of the major scientific obstacles we are facing in the development of an effective HIV vaccine, and discusses recent progresses in the field with a focus on current approaches toward a neutralizing antibody-based HIV vaccine. The bioorganic aspects of the approaches are emphasized.
全球范围内的艾滋病毒/艾滋病流行促使人们研发一种有效的疫苗。大约二十年前，随着艾滋病毒被确认为艾滋病的病因，人们曾一度期望预防性疫苗能很快问世。但艾滋病毒包膜糖蛋白gp120作为预防性疫苗的早期前景并未实现。广泛中和抗体和艾滋病毒特异性细胞毒性T淋巴细胞（CTL）是有效艾滋病毒疫苗可能必须引发的两种免疫效应物。动物模型实验证明，足够水平的中和抗体可以清除病毒并保护动物免受病毒攻击。因此，诱导广泛中和抗体反应仍然是艾滋病毒疫苗研发的主要目标。为了实现持续感染，艾滋病毒已经进化出巧妙的策略来逃避宿主免疫监视。这些策略包括包膜寡聚化、快速突变、高度糖基化和构象变化。艾滋病毒防御的每一个层面都增加了复杂性，为了研发出一种能提供强大而持久免疫力的疫苗，必须考虑到这些复杂性。近年来，在了解艾滋病毒包膜结构和艾滋病毒逃避免疫系统的分子机制方面取得了重要进展。这反过来极大地促进了能够引发针对艾滋病毒的广泛中和抗体的免疫原的合理设计。本综述概述了我们在研发有效艾滋病毒疫苗过程中面临的主要科学障碍，并讨论了该领域的最新进展，重点是基于中和抗体的艾滋病毒疫苗的当前方法。文中强调了这些方法的生物有机方面。
