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Control of SHIV-89.6P-infection of cynomolgus monkeys by HIV-1 Tat protein vaccine

Abstract

Vaccine strategies aimed at blocking virus entry have so far failed to induce protection against heterologous viruses. Thus, the control of viral infection and the block of disease onset may represent a more achievable goal of human immunodeficiency virus (HIV) vaccine strategies. Here we show that vaccination of cynomolgus monkeys with a biologically active HIV-1 Tat protein is safe, elicits a broad (humoral and cellular) specific immune response and reduces infection with the highly pathogenic simian-human immunodeficiency virus (SHIV)-89.6P to undetectable levels, preventing the CD4+ T-cell decrease. These results may provide new opportunities for the development of a vaccine against AIDS.

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Figure 1: Humoral responses to Tat.
Figure 2: Lymphoproliferative responses.
Figure 3: Detection of viral infection up to 28 weeks after challenge with SHIV-89.
Figure 4: Detection of viral infection after challenge with SHIV-89.6P.
Figure 5: Titers of antibody against HIV-2/SIV up to 28 weeks after challenge with SHIV-89.
Figure 6: CD4+ and CD8+ T-cell counts up to 28 weeks after challenge with SHIV-89.

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Acknowledgements

We thank all personnel responsible of the animal facility; C. Sgadari, D. Negri, I. Macchia, Z. Michelini, M. Barbisin, E. Salvi and C. Rovetto (Laboratory of Virology, Istituto Superiore di Sanità, Rome, Italy) for technical help; P. Markham and B.C. Nair (Advanced BioScience laboratories, Kensington, Maryland) for Tat protein production; A. Lippa and F. M. Regini for editorial assistance; and G. Benagiano (Director General, ISS, Rome, Italy) for his support to the study. This work was supported by Italian grants from the ISS, Rome, Italy, IX AIDS Project and from the Associazione Nazionale per la Lotta contro l'AIDS (ANLAIDS).

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Correspondence to Barbara Ensoli.

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Cafaro, A., Caputo, A., Fracasso, C. et al. Control of SHIV-89.6P-infection of cynomolgus monkeys by HIV-1 Tat protein vaccine. Nat Med 5, 643–650 (1999). https://doi.org/10.1038/9488

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