Innate protection against intrarectal SIV acquisition by a live SHIV vaccine

Author:

Sui, Yongjun

Meyer, Thomas J

Fennessey,Christine

Keele,Brandon

Dadkhah,Kimia

Ma, Chi

LaBranche, Celia C

Breed, Matthew W

Kramer,Josh

Li, Jianping

Howe, Savannah E

Ferrari, Guido

Williams, LaTonya D

Cam, Maggie

Kelly,Michael

Shen, Xiaoying

Tomaras, Georgia D

Montefiori, David

Greten, Tim F

Miller, Christopher J

Berzofsky, Jay A
Author Address

Vaccine Branch and., CCR Collaborative Bioinformatics Resource, National Cancer Institute, NIH, Bethesda, Maryland, USA., AIDS and Cancer Virus Program and., Single Cell Analysis Facility, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA., Thoracic and GI Malignancies Branch, National Cancer Institute, NIH, Bethesda, Maryland, USA., Duke Human Vaccine Institute and., Department of Surgery, Duke University School of Medicine, Durham, North Carolina, USA., Laboratory Animal Sciences Program, Frederick National Laboratory for Cancer Research, Bethesda, Maryland, USA., Duke Center for Human Systems Immunology, Duke University School of Medicine, Durham, North Carolina, USA., Center for Comparative Medicine, University of California, Davis, Davis, California, USA.,

Abstract:

Identifying immune correlates of protection is a major challenge in AIDS vaccine development. Anti-Envelope antibodies have been considered critical for protection against SIV/HIV (SHIV) acquisition. Here, we evaluated the efficacy of an SHIV vaccine against SIVmac251 challenge, where the role of antibody was excluded, as there was no cross-reactivity between SIV and SHIV envelope antibodies. After 8 low-dose intrarectal challenges with SIVmac251, 12 SHIV-vaccinated animals demonstrated efficacy, compared with 6 naive controls, suggesting protection was achieved in the absence of anti-envelope antibodies. Interestingly, CD8+ T cells (and some NK cells) were not essential for preventing viral acquisition, as none of the CD8-depleted macaques were infected by SIVmac251 challenges. Initial investigation of protective innate immunity revealed that protected animals had elevated pathways related to platelet aggregation/activation and reduced pathways related to interferon and responses to virus. Moreover, higher expression of platelet factor 4 on circulating platelet-leukocyte aggregates was associated with reduced viral acquisition. Our data highlighted the importance of innate immunity, identified mechanisms, and may provide opportunities for novel HIV vaccines or therapeutic strategy development.

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Author Address