HIV vaccine R&D shifts from development to discovery

Aug. 27, 2008

Events of the past year in HIV vaccine research have led some to question whether an effective HIV vaccine will ever be developed. In the August 28 edition of the New England Journal of Medicine, officials from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, examine the extraordinarily challenging properties of the virus that have made a vaccine elusive and outline the scientific questions that, if answered, could lead to an effective HIV vaccine.

In recent years, the most extensively studied HIV vaccines have aimed to mobilize immune cells called T cells, write Anthony S. Fauci, M.D., NIAID director, and Margaret I. Johnston, Ph.D., director of the Vaccine Research Program in NIAID's Division of AIDS. T-cell vaccines are not expected to prevent HIV infection. Rather, they could potentially reduce the level of virus (but not eliminate it) following infection, limit the number of immune cells that HIV destroys, and thus delay the progression to AIDS. There is no evidence yet that T-cell HIV vaccines work in humans, however. If the vaccines ultimately do, their effectiveness may vary greatly depending on the genetic make-up of each individual, given that T-cell immunity is dependent on genetic factors. Furthermore, because the virus would persist in the blood of vaccinated individuals, T-cell vaccines would likely generate only transient "herd immunity"—that is, population-wide protection from disease conferred by vaccination of a percentage of the community.

In response to the failure last September of a T-cell vaccine for which many people had high hopes, the HIV vaccine field has undergone a self-reexamination and has determined that the balance between fundamental discovery research and product development should shift toward discovery. In particular, future research must intensify the study of broadly neutralizing antibodies to HIV, why most HIV-infected people do not make them, and the design of novel strategies to induce them with a vaccine. Also, studying the earliest stages of HIV infection may shed light on ways to manipulate innate and mucosal immune responses to widen the window of opportunity for viral eradication, to prevent the virus from advancing to gut-associated lymphoid tissue, or both.

The authors conclude with cautious optimism that an effective HIV vaccine will be developed, but will depend on the significant growth of scientific understanding of HIV disease and human responses to the virus.

ARTICLE: MI Johnston and AS Fauci. An HIV vaccine--challenges and prospects. New England Journal of Medicine DOI: 10.1056/NEJMp0806162 (2008).

WHO: Anthony S. Fauci, M.D., director of NIAID, and Margaret I. Johnston, Ph.D., the director of the Vaccine Research Program in NIAID's Division of AIDS, are available to comment on this article.

NIH/National Institute of Allergy and Infectious Diseases, http://www.niaid.nih.gov.

SOURCE: NIH

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