Richard A. Koup, Barney S. Graham and Daniel C. Douek are at the Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-3017, USA.
Nat Rev Immunol. 2011 Jan;11(1):65-70. doi: 10.1038/nri2890. Epub 2010 Dec 17.
Even before the partial success of a preventive HIV vaccine in a recent Phase III clinical trial, there had been an active research effort to determine one or more immune correlates of protection for HIV infection. This effort has been hampered by the lack of natural protective immunity against HIV. As a result, most of the studies have focused on long-term non-progressive infection or other clinical situations, none of which fully recapitulates protective immunity against HIV. Although this effort has been successful in defining characteristics of T cells in acute and non-progressive HIV infection, and has therefore greatly expanded our knowledge of the immunopathogenesis of AIDS, its success in defining immune correlates of protection is less clear. In this Opinion article we offer a perspective on how successful this effort has been in defining immune correlates of protection that have been, or will be, of use in the development of an HIV vaccine. Our view is that investing in an iterative approach to human vaccine efficacy trials of sufficient size and sampling frequency will improve the likelihood that an immune correlate of vaccine protection will be defined.
即使在最近的 III 期临床试验中一种预防性 HIV 疫苗取得部分成功之前，人们已经积极努力确定一个或多个 HIV 感染的免疫保护相关因素。由于缺乏针对 HIV 的自然保护性免疫，这项工作受到了阻碍。因此，大多数研究都集中在长期非进展性感染或其他临床情况上，这些都没有完全再现对 HIV 的保护性免疫。尽管这项工作成功地定义了急性和非进展性 HIV 感染中 T 细胞的特征，从而极大地扩展了我们对艾滋病发病机制的认识，但它在定义保护性免疫相关因素方面的成功并不那么明显。在这篇观点文章中，我们提供了一个视角，说明这项工作在定义已经或将要用于开发 HIV 疫苗的保护性免疫相关因素方面取得了多大的成功。我们的观点是，投资于足够规模和采样频率的人类疫苗功效试验的迭代方法将提高定义疫苗保护免疫相关因素的可能性。
