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

Author

Listed:
  • 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
    Ragon Institute of MGH, MIT and Harvard)

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.

Suggested Citation

  • Brandon F. Keele & Wenjun Li & Erica N. Borducchi & Joseph P. Nkolola & Peter Abbink & Bing Chen & Michael S. Seaman & Dan H. Barouch, 2017. "Adenovirus prime, Env protein boost vaccine protects against neutralization-resistant SIVsmE660 variants in rhesus monkeys," Nature Communications, Nature, vol. 8(1), pages 1-9, August.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15740
    DOI: 10.1038/ncomms15740
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