Department of Medicine, Division of Preventive and Behavioral Medicine
Immunity | Immunoprophylaxis and Therapy | Virology | Virus Diseases | Viruses
Previous 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 TRIM5alpha 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.
Adaptive immunity, HIV infections, Vaccines
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Copyright © 2017, The Author(s)
DOI of Published Version
Nat Commun. 2017 Jun 5;8:15740. doi: 10.1038/ncomms15740. Link to article on publisher's site
Keele, Brandon F.; Li, Wenjun; Borducchi, Erica N.; Nkolola, Joseph P.; Abbink, Peter; Chen, Bing; Seaman, Michael S.; and Barouch, Dan H., "Adenovirus prime, Env protein boost vaccine protects against neutralization-resistant SIVsmE660 variants in rhesus monkeys" (2017). Open Access Articles. 3188.
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