Adenovirus prime, Env protein boost vaccine protects against neutralization-resistant SIVsmE660 variants in rhesus monkeys
AuthorsKeele, Brandon F.
Borducchi, Erica N.
Nkolola, Joseph P.
Seaman, Michael S.
Barouch, Dan H.
UMass Chan AffiliationsDepartment of Medicine, Division of Preventive and Behavioral Medicine
Immunoprophylaxis and Therapy
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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 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.
SourceNat Commun. 2017 Jun 5;8:15740. doi: 10.1038/ncomms15740. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/40383
RightsCopyright © 2017, The Author(s)