You can manage bookmarks using lists, please log in to your user account for this.
Media type:
E-Article
Title:
Adenovirus prime, Env protein boost vaccine protects against neutralization-resistant SIVsmE660 variants in rhesus monkeys
Contributor:
Keele, Brandon F.;
Li, Wenjun;
Borducchi, Erica N.;
Nkolola, Joseph P.;
Abbink, Peter;
Chen, Bing;
Seaman, Michael S.;
Barouch, Dan H.
Published:
Springer Science and Business Media LLC, 2017
Published in:
Nature Communications, 8 (2017) 1
Language:
English
DOI:
10.1038/ncomms15740
ISSN:
2041-1723
Origination:
Footnote:
Description:
AbstractPrevious studies have shown that DNA prime, Ad5 boost vaccines protect against neutralization-sensitive but not neutralization-resistant virus variants within the SIVsmE660 swarm. Here we show that Ad prime, Env protein boost vaccines protect against neutralization-resistant SIVsmE660 variants. We perform two studies in rhesus monkeys with Ad35/Ad26 vectors expressing SIVmac239 Gag/Pol/Env with or without an AS01B-adjuvanted SIVmac32H gp140 protein boost. In a repetitive, low-dose challenge study, we observe robust protection against acquisition of infection by both Ad Alone and Ad/Env vaccines. In a single, high-dose challenge study, only the Ad/Env vaccine affords significant protection against acquisition of infection. Analysis of transmitted/founder (T/F) viruses from this study demonstrates that the Ad/Env vaccine blocks both neutralization-sensitive and neutralization-resistant SIVsmE660 variants in rhesus monkeys with restrictive TRIM5α alleles. These data demonstrate that the adjuvanted Env protein boost is critical for protecting against high-dose SIVsmE660 challenge and for blocking neutralization-resistant viruses within the SIVsmE660 swarm.