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

Monica Vaccari; Brandon F. Keele; Steven Bosinger; Melvin N. Doster; Zhong-Min Ma; Justin  Pollara; Anna Hryniewicz; Guido Ferrari; Yongjun Guan; Donald N.  Forthal; David Venzon; Claudio  Fenizia; Tia  Morgan; David  Montefiori; Jeffrey D. Lifson; Chris J. Miller; Guido Silvestri; Margherita Rosati; Barbara K. Felber; George N. Pavlakis; James Tartaglia; Genoveffa Franchini

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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

Monica Vaccari, National Cancer Institute

Brandon F. Keele, Frederick National Laboratory for Cancer Research

Steven Bosinger, Emory University

Melvin N. Doster, National Cancer Institute

Zhong-Min Ma, University of California Davis

Justin Pollara, Duke University

Anna Hryniewicz, National Cancer Institute

Guido Ferrari, Duke University

Yongjun Guan, Univ Maryland

Donald N. Forthal, University of California Irvine

David Venzon, National Cancer Institute

Claudio Fenizia, National Cancer Institute

Tia Morgan, National Cancer Institute

David Montefiori, Duke University

Jeffrey D. Lifson, Frederick National Laboratory for Cancer Research

Chris J. Miller, University of California Davis

Guido Silvestri, Emory University

Margherita Rosati, Frederick National Laboratory for Cancer Research,

Barbara K. Felber, Frederick National Laboratory for Cancer Research,

George N. Pavlakis, Frederick National Laboratory for Cancer Research

James Tartaglia, Sanofi Pasteur Inc

Genoveffa Franchini, National Cancer Institute

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Journal Title:

Journal of Virology

Volume:

Volume 87, Number 6

Publisher:

American Society for Microbiology | 2013-03-01, Pages 3538-3548

Type of Work:

Article | Final Publisher PDF

Permanent URL:

https://pid.emory.edu/ark:/25593/s26w4

Publisher DOI:

http://doi.org/10.1128/JVI.02863-12

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).

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

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