Protection afforded by an HIV vaccine candidate in macaques depends on the dose of SIVmac251 at challenge exposure

Monica Vaccari, Brandon F. Keele, Steven E. 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 & 2 others James Tartaglia, Genoveffa Franchini

Research output: Contribution to journalArticle

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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).

Original languageEnglish (US)
Pages (from-to)3538-3548
Number of pages11
JournalJournal of Virology
Volume87
Issue number6
DOIs
StatePublished - Mar 2013

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Simian immunodeficiency virus
Simian Immunodeficiency Virus
Human immunodeficiency virus
Macaca
Vaccines
HIV
vaccines
dosage
Interferons
Genes
Immunization
alum
Theoretical Models
Up-Regulation
Down-Regulation
interferons
T-Lymphocytes
B-lymphocytes
DNA
immunization

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Vaccari, M., Keele, B. F., Bosinger, S. E., Doster, M. N., Ma, Z. M., Pollara, J., ... Franchini, G. (2013). Protection afforded by an HIV vaccine candidate in macaques depends on the dose of SIVmac251 at challenge exposure. Journal of Virology, 87(6), 3538-3548. https://doi.org/10.1128/JVI.02863-12

Protection afforded by an HIV vaccine candidate in macaques depends on the dose of SIVmac251 at challenge exposure. / Vaccari, Monica; Keele, Brandon F.; Bosinger, Steven E.; Doster, Melvin N.; Ma, Zhong Min; Pollara, Justin; Hryniewicz, Anna; Ferrari, Guido; Guan, Yongjun; Forthal, Donald N.; Venzon, David; Fenizia, Claudio; Morgan, Tia; Montefiori, David; Lifson, Jeffrey D.; Miller, Chris J; Silvestri, Guido; Rosati, Margherita; Felber, Barbara K.; Pavlakis, George N.; Tartaglia, James; Franchini, Genoveffa.

In: Journal of Virology, Vol. 87, No. 6, 03.2013, p. 3538-3548.

Research output: Contribution to journalArticle

Vaccari, M, Keele, BF, Bosinger, SE, Doster, MN, Ma, ZM, Pollara, J, Hryniewicz, A, Ferrari, G, Guan, Y, Forthal, DN, Venzon, D, Fenizia, C, Morgan, T, Montefiori, D, Lifson, JD, Miller, CJ, Silvestri, G, Rosati, M, Felber, BK, Pavlakis, GN, Tartaglia, J & Franchini, G 2013, 'Protection afforded by an HIV vaccine candidate in macaques depends on the dose of SIVmac251 at challenge exposure', Journal of Virology, vol. 87, no. 6, pp. 3538-3548. https://doi.org/10.1128/JVI.02863-12
Vaccari, Monica ; Keele, Brandon F. ; Bosinger, Steven E. ; Doster, Melvin N. ; Ma, Zhong Min ; Pollara, Justin ; Hryniewicz, Anna ; Ferrari, Guido ; Guan, Yongjun ; Forthal, Donald N. ; Venzon, David ; Fenizia, Claudio ; Morgan, Tia ; Montefiori, David ; Lifson, Jeffrey D. ; Miller, Chris J ; Silvestri, Guido ; Rosati, Margherita ; Felber, Barbara K. ; Pavlakis, George N. ; Tartaglia, James ; Franchini, Genoveffa. / Protection afforded by an HIV vaccine candidate in macaques depends on the dose of SIVmac251 at challenge exposure. In: Journal of Virology. 2013 ; Vol. 87, No. 6. pp. 3538-3548.
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