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The quest for a T cell-based immune correlate of protection against HIV: a story of trials and errors

Nature Reviews Immunology volume 11, pages 65–70 (2011)Cite this article

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Abstract

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.

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Figure 1: Conventional and adaptive trial design.

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Acknowledgements

We thank the many members of the Vaccine Research Center whose helpful discussions over the years have helped to frame the opinions expressed here.

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  1. 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.,

    Richard A. Koup, Barney S. Graham & Daniel C. Douek

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Correspondence to Daniel C. Douek.

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Koup, R., Graham, B. & Douek, D. The quest for a T cell-based immune correlate of protection against HIV: a story of trials and errors. Nat Rev Immunol 11, 65–70 (2011). https://doi.org/10.1038/nri2890

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