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Author Notes:

Address correspondence to Genoveffa Franchini, franchinq@mail.nih.gov

We thank N. Letvin, J. Mascola, and M. Roederer for providing the SIVmac251 virus stock, J. Treece, D. Weiss, and P. Markham for animal husbandry and care, V. Kalyanaraman and L. Ajayi for antibody binding assays, H. K. Chung and E. Lee for the quantitative analysis of viral RNA and DNA, and Teresa Habina for manuscript editing.

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Research Funding:

This work was supported with federal funds from the National Cancer Institute, National Institutes of Health, and in part with contract no. HHSN261200800001E.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Virology
  • VIROLOGY
  • SIMIAN IMMUNODEFICIENCY VIRUS
  • AFRICAN-GREEN MONKEYS
  • CD8(+) T-CELLS
  • RHESUS MACAQUES
  • IMMUNE-RESPONSES
  • SIVAGM INFECTION
  • DNA VACCINATION
  • ALVAC
  • AIDS
  • REPLICATION

Protection Afforded by an HIV Vaccine Candidate in Macaques Depends on the Dose of SIVmac251 at Challenge Exposure

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Journal Title:

Journal of Virology

Volume:

Volume 87, Number 6

Publisher:

, Pages 3538-3548

Type of Work:

Article | Final Publisher PDF

Abstract:

We used the simian immunodeficiency virus mac251 (SIVmac251) macaque model to study the effect of the dose of mucosal exposure on vaccine efficacy. We immunized macaques with a DNA prime followed by SIV gp120 protein immunization with ALVAC-SIV and gp120 in alum, and we challenged them with SIVmac251 at either a single high dose or at two repeated low-dose exposures to a 10-fold-lower dose. Infection was neither prevented nor modified following a single high-dose challenge of the immunized macaques. However, two exposures to a 10-fold-lower dose resulted in protection from SIVmac251 acquisition in 3 out of 12 macaques. The remaining animals that were infected had a modulated pathogenesis, significant downregulation of interferon responsive genes, and upregulation of genes involved in B- and T-cell responses. Thus, the choice of the experimental model greatly influences the vaccine efficacy of vaccines for human immunodeficiency virus (HIV).

Copyright information:

© 2013, American Society for Microbiology. All Rights Reserved.

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