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Science 19 June 1998:
Vol. 280. no. 5371, pp. 1875 - 1880
DOI: 10.1126/science.280.5371.1875
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Articles

Progress in the Development of an HIV-1 Vaccine

Norman L. Letvin

Containment of the acquired immunodeficiency syndrome (AIDS) epidemic will require an effective human immunodeficiency virus type 1 (HIV-1) vaccine. Accumulating evidence suggests that such a vaccine must efficiently elicit an HIV-1-specific cytotoxic T lymphocyte (CTL) response. Nonhuman primate models will continue to provide an important tool for assessing the extent of protective immunity induced by various immunization strategies. Although replication-competent AIDS viruses attenuated for pathogenicity by selective gene deletions have provided protective immunity in nonhuman primate models, the long-term safety of such vaccines in human populations is suspect. Inactivated virus and subunit vaccines have elicited neither CTLs nor antibodies capable of neutralizing a wide array of patient HIV-1 isolates. Considerable effort is now being focused on evaluating live vector-based vaccine and plasmid DNA vaccine approaches for preventing HIV-1 infection both in animal model and human studies. Our growing understanding of the biology of HIV-1 and immune responses to this virus will continue to suggest improved vaccination approaches for exploration.

The author is at Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA. E-mail: nletvin{at}bidmc.harvard.edu

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Linear Differentiation of Cytotoxic Effectors into Memory T Lymphocytes.
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D. H. Barouch, A. Craiu, M. J. Kuroda, J. E. Schmitz, X. X. Zheng, S. Santra, J. D. Frost, G. R. Krivulka, M. A. Lifton, C. L. Crabbs, et al. (2000)
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Science. ISSN 0036-8075 (print), 1095-9203 (online)