AEGiS-14IAC: Comparison of protective efficacies between Gag- and Tat-boosters in a DNA-prime/ Sendai viral vector-boost vaccine system against AIDS.

14th International AIDS Conference

Barcelona, Spain - July 7-12, 2002

Comparison of protective efficacies between Gag- and Tat-boosters in a DNA-prime/ Sendai viral vector-boost vaccine system against AIDS.

Int Conf AIDS 2002 Jul 7-12; 14:(abstract no. TuOrA1221)

Matano T, Kano M, Lun WH, Nakamura H, Takeda A, Ami Y, Nagai Y
Department of Microbiology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan

Backgrounds: Cellular immune responses play a critical role in the control of immunodeficiency virus infections. We previously developed a proviral DNA vaccine system using an env- and nef-deleted simian-human immunodeficiency virus (SHIV) proviral DNA. Further, we established an efficient antigen-expression system using Sendai virus vector (SeV). Then, we combined these two systems to develop a DNA-prime/Gag-expressing SeV (SeV-Gag)-boost vaccine and showed its excellent protective efficacy against acute AIDS in a macaque model. Recently, the potential of viral early regulatory proteins such as Tat for inducing effective immune responses has been stressed. In this study, we compared the protective efficacies between Gag- and Tat-boosters in our DNA-prime/SeV-boost system.

METHODS: Rhesus macaques (14 in total) were divided into four groups; they were naïve (group I), or vaccinated with DNA alone (group II), with DNA-prime/SeV-Gag-boost (group III), or with DNA-prime/Tat-expressing SeV (SeV-Tat)-boost (group IV), and challenged intravenously with a pathogenic SHIV89.6PD.

RESULTS: The DNA-prime/SeV-Gag-boost efficiently induced SHIV-specific CD4+ T and CD8+ T cells, while the SeV-Tat-booster resulted in significant expansion of specific CD4+ T cells but not of CD8+ T cells. All the group III macaques showed greatly reduced viral loads compared with controls and were protected from acute CD4+ T-cell depletion and progression to acute AIDS. In contrast, some of the group IV macaques showed transient acute CD4 depletion, although all of them were protected from disease progression. Thus, they showed similar levels of protection as compared with the group II.

CONCLUSION: The DNA-prime/SeV-Gag-boost regimen lead to rapid control of immunodeficiency virus infections in a macaque AIDS model. Thus, it would be a promising AIDS vaccine candidate. In contrast, boost by Tat alone was not so effective in our strategy.

Keywords: AEGIS, Acquired Immunodeficiency Syndrome, Viral Vaccines, AIDS Vaccines, Simian Acquired Immunodeficiency Syndrome, Vaccines, DNA, Viral Load, Macaca mulatta, Sendai virus, Macaca, Lymphocyte Depletion, T-Lymphocytes, Genetic Vectors, Animal, Human, virology, immunology, genetics

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TuOrA1221