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

• Type of Material: Article
• Authors: 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
• Language: English
• Date: 2013-03-01
• Publisher: American Society for Microbiology
• Publication Version: Final Published Version
• Copyright Statement: © 2013, American Society for Microbiology. All Rights Reserved.
• Final Published Version (URL): http://dx.doi.org/10.1128/JVI.02863-12
• Title of Journal or Parent Work: Journal of Virology
• ISSN: 0022-538X
• Volume: 87
• Issue: 6
• Start Page: 3538
• End Page: 3548
• Grant/Funding Information: This work was supported with federal funds from the National Cancer Institute, National Institutes of Health, and in part with contract no. HHSN261200800001E.
• Keywords: RHESUS MACAQUES; CD8(+) T-CELLS; REPLICATION; AFRICAN-GREEN MONKEYS; VIROLOGY; DNA VACCINATION; Life Sciences & Biomedicine; Science & Technology; SIMIAN IMMUNODEFICIENCY VIRUS; SIVAGM INFECTION; ALVAC; IMMUNE-RESPONSES; AIDS; Virology
• Research Categories: Health Sciences, Immunology; Health Sciences, Public Health

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).