Adenovirus prime, Env protein boost vaccine protects against neutralization-resistant SIVsmE660 variants in rhesus monkeys

Brandon F. Keele, Wenjun Li, Erica N. Borducchi, Joseph P. Nkolola, Peter Abbink, Bing Chen, Michael S. Seaman and Dan H. Barouch ()
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Brandon F. Keele: AIDS and Cancer Virus Program, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research
Wenjun Li: University of Massachusetts Medical School
Erica N. Borducchi: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center
Joseph P. Nkolola: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center
Peter Abbink: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center
Bing Chen: Children’s Hospital
Michael S. Seaman: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center
Dan H. Barouch: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center

Nature Communications, 2017, vol. 8, issue 1, 1-9

Abstract: Abstract 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 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.

Date: 2017
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DOI: 10.1038/ncomms15740

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