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 language | English (US) |
|---|---|
| Pages (from-to) | 3538-3548 |
| Number of pages | 11 |
| Journal | Journal of Virology |
| Volume | 87 |
| Issue number | 6 |
| DOIs | |
| State | Published - Mar 2013 |
Fingerprint
ASJC Scopus subject areas
- Immunology
- Virology
Cite this
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 journal › Article
}
TY - JOUR
T1 - Protection afforded by an HIV vaccine candidate in macaques depends on the dose of SIVmac251 at challenge exposure
AU - Vaccari, Monica
AU - Keele, Brandon F.
AU - Bosinger, Steven E.
AU - Doster, Melvin N.
AU - Ma, Zhong Min
AU - Pollara, Justin
AU - Hryniewicz, Anna
AU - Ferrari, Guido
AU - Guan, Yongjun
AU - Forthal, Donald N.
AU - Venzon, David
AU - Fenizia, Claudio
AU - Morgan, Tia
AU - Montefiori, David
AU - Lifson, Jeffrey D.
AU - Miller, Chris J
AU - Silvestri, Guido
AU - Rosati, Margherita
AU - Felber, Barbara K.
AU - Pavlakis, George N.
AU - Tartaglia, James
AU - Franchini, Genoveffa
PY - 2013/3
Y1 - 2013/3
N2 - 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).
AB - 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).
UR - http://www.scopus.com/inward/record.url?scp=84874670092&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84874670092&partnerID=8YFLogxK
U2 - 10.1128/JVI.02863-12
DO - 10.1128/JVI.02863-12
M3 - Article
VL - 87
SP - 3538
EP - 3548
JO - Journal of Virology
JF - Journal of Virology
SN - 0022-538X
IS - 6
ER -