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Innate protection against intrarectal SIV acquisition by a live Simian-Human immunodeficiency virus vaccine

ABSTRACT: Identifying immune correlates of protection is a major challenge in AIDS vaccine development. Anti-Envelope antibodies have been considered critical against SIV/HIV acquisition. Here, we evaluated the efficacy of a 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 eight low-dose rectal challenges with SIVmac251, 12 SHIV-vaccinated animals demonstrated 83% efficacy, compared to six naïve controls, suggesting protection could be achieved in the absence of anti-Envelope antibodies. Interestingly, CD8+ T cells (and some NK cells) were not essential for the 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 (PF4) on circulating platelet-leukocyte aggregates was associated with reduced viral acquisition. Our data highlighted the importance of innate immunity and may provide new opportunities for novel HIV vaccines or therapeutic strategy development.

ORGANISM(S): Macaca mulatta

PROVIDER: GSE242726 | GEO | 2024/09/30

REPOSITORIES: GEO

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Innate protection against intrarectal SIV acquisition by a live Simian HIV vaccine

Project description:Identifying immune correlates of protection is a major challenge in AIDS vaccine development. Anti-Envelope antibodies have been considered critical against SIV/HIV acquisition. Here, we evaluated the efficacy of a 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 eight low-dose rectal challenges with SIVmac251, 12 SHIV-vaccinated animals demonstrated 83% efficacy, compared to six naïve controls, suggesting protection could be achieved in the absence of anti-Envelope antibodies. Interestingly, CD8+ T cells (and some NK cells) were not essential for the preventing viral acquisition, as none of the CD8-depleted macaques was 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 (PF4) on circulating platelet-leukocyte aggregates was associated with reduced viral acquisition. Our data highlighted the importance of innate immunity and may provide new opportunities for novel HIV vaccines or therapeutic strategy development.

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