Paula Grasberger

This session featured talks on immune correlates of vaccine efficacy from the Imbokodo HIV-1 vaccine trial, the use of a Flt3 agonist to enhance immunogenicity of arenavirus-vector vaccines, and identifying metabolomic and lipidomic correlates of time to HIV rebound following ART interruption.

Avi Kenny (University of Washington) presented an analysis of immune correlates from the Imbokodo HIV-1 vaccine trial (HTVN705/HPX2008), which tested a regimen of a vector-based vaccine (Ad26.Mo4.HIV) in combination with clade C gp140 protein. While the vaccine was not effective and six primary immune markers (mainly analyzing antibody responses) did not yield any statistically significant correlates of risk/protection, there is a trend for IgG3 V1V2 breadth as an inverse correlate of risk. Dr. Brie Falkard (Gilead) presented data demonstrating that dosing rhesus macaques with a Flt3 receptor agonist (GS-3583) 7 days prior to alternating arenavirus vectors encoding SIV immunogens, increased the number of blood dendritic cells and monocytes, as compared to treating with alternating arenavirus vectors alone. T cell response magnitude/breadth and polyfunctionality were significantly increased. An increase in Env-binding antibodies was also observed. Dr. Yanhui Cai (Gilead) showed several metabolic pathways are upregulated following treatment with the TLR7 agonist, vesatolimod, including pro-inflammatory tryptophan synthesis and aminoacyl-tRNA biosynthesis. Levels of glycousodeoxycholic acid, ceramide lipid group, and cholesterol ester were associated with longer time to HIV rebound (following ART interruption) and a greater decrease in intact proviral DNA. L-phenylalanine, phosphatidylcholine, and phosphatidylethanolamine were associated with shorter time to HIV rebound.

IgG3 V1V2 breadth as a potential inverse correlate of risk warrants further investigation; perhaps in a study with greater vaccine efficacy, significance could be achieved. Other trials have shown evidence of IgG3 or V1V2 epitope correlation with efficacy. Using a Flt3 receptor agonist in combination with alternating arenavirus vectors encoding SIV immunogens shows promise in generating a robust, polyfunctional T cell response, which may work in conjunction with antibodies to prevent infection. There is potential to use lipid/metabolite signatures as markers to predict time to HIV rebound following ART interruption in clinical trials.