{Reference Type}: Journal Article
{Title}: Innate protection against intrarectal SIV acquisition by a live SHIV vaccine.
{Author}: Sui Y;Meyer TJ;Fennessey CM;Keele BF;Dadkhah K;Ma C;LaBranche CC;Breed MW;Kramer JA;Li J;Howe SE;Ferrari G;Williams LD;Cam M;Kelly MC;Shen X;Tomaras GD;Montefiori D;Greten TF;Miller CJ;Berzofsky JA;
{Journal}: JCI Insight
{Volume}: 9
{Issue}: 12
{Year}: 2024 May 21
{Factor}: 9.484
{DOI}: 10.1172/jci.insight.175800
{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.