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Progress and obstacles in the development of an AIDS vaccine

Nature Reviews Immunology volume 6, pages 930–939 (2006)Cite this article

Key Points

  • With five million new infections with HIV-1 occurring each year, the development of an effective vaccine against HIV-1 remains an absolute priority.

  • Because of the rapid generation of mutant viruses, HIV-1 exists as a swarm or viral quasi-species, even in a single infected individual.

  • Immune containment of HIV-1 is mediated predominantly by cellular rather than humoral immune responses. It is probable that both mucosal and systemic immune responses will be required for a vaccine to be effective.

  • Vaccine strategies can only be evaluated in non-human primate models.

  • Before an effective vaccine can be generated, there are various problems that must be overcome. For example, a means of generating broadly neutralizing antibodies, and of inducing mucosal immune responses, is needed. A way to deal with the extraordinary genetic diversity of the virus must also be found, as must some means of eliciting durable, potent immune responses.

Abstract

Recent experimental observations suggest approaches to immunization that might finally result in at least a partially effective vaccine against infection with HIV-1. In particular, advances in our understanding of the contribution of vaccine-elicited cellular immunity to protecting memory CD4+ T cells from virus-mediated destruction provide rational strategies for the development of this vaccine. This is therefore an ideal time to review our current understanding of HIV-1 and its control by the immune system, as well as the remaining problems that must be solved to facilitate the development of an effective vaccine against AIDS.

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Figure 1: Prevalence of HIV-1 infections in different geographical regions worldwide.
Figure 2: Immune responses following HIV-1 infection.
Figure 3: Molecular mechanisms of HIV-1 genetic variation.
Figure 4: Genetic diversity of HIV-1 isolates.

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Acknowledgements

The author thanks J. Mascola and B. Hahn for their careful review of this manuscript and B. Korber for providing Figure 4. This work was supported by the US National Institutes of Health.

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  1. Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, 02215, Massachusetts, USA

    Norman L. Letvin

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FURTHER INFORMATION

Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center

HIV Databases

Ongoing trials of preventative AIDS vaccines

Glossary

Lentiviruses

A genus of slow viruses, which are characterized by long incubation periods, of the Retroviridae family that includes HIV-1 and SIV.

Neutralizing antibody

An antibody that reacts with an infectious agent, usually a virus, and destroys or inhibits its infectiveness.

Prime–boost vaccination

When a single application of a vaccine is insufficient, repeated immunizations are performed using either the same vaccine preparation (homologous prime–boost) or different vaccine preparations (heterologous prime–boost) to stimulate a better immune response. Prior exposure to one strain diverts the antibody response to shared epitopes of a second strain after exposure.

Immunogenicity

The ability to provoke overt immune responses.

Liposomes

A lipid vesicle that encapsulates vaccines in a lipid bilayer membrane and facilitates their delivery.

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Letvin, N. Progress and obstacles in the development of an AIDS vaccine. Nat Rev Immunol 6, 930–939 (2006). https://doi.org/10.1038/nri1959

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