Enhance HIV Vaccine Efficacy by Mucosal Adjuvant: Unraveling Aryl Hydrocarbon Receptor Agonists in Boosting Antiviral NK Cell Responses in Prophylactic HIV Vaccines
Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B199
Abstract ID: 5950
Presenting Author:
Namal Liyanage , Assistant Professor at Ohio State Univ. Col. of Med.
Abstract:
The RV144 vaccine trial is the sole HIV vaccine regimen to demonstrate protection, with an efficacy of 31.2%. Antibody-dependent cell-mediated cytotoxicity (ADCC) correlated with its protection. NK cells and antibodies are the primary mediators of ADCC. Enhancing ADCC may be crucial for optimizing vaccine efficacy. We previously showed that aryl hydrocarbon receptor (AHR) agonists enhance NK cell effector functions. Here, we investigate the potential of the AHR agonist indol-3-carbinol (I3C) to enhance the effector functions of NK cells, thereby amplifying ADCC capability. C57BL/6 mice were categorized into two groups and administered either the RV144 vaccine regimen alone (n=6) or the vaccine with daily oral administration of I3C (n=6). Through flow cytometric analysis of immune signatures and bulk RNA-sequencing, we found significantly elevated KLRG1+ NK cells in the I3C group in multiple tissues. KLRG1+ NK cells are considered potent mediators of robust ADCC. We also found elevated Ly6C (enabling effective and robust responses to infection) and CD11b (indicating mature cytolytic activity) in KLRG1+ NK cells. IL1β and TNFα, critical for lysis during ADCC, were increased in this subset. Transcriptomics revealed upregulated fcgr3, encoding for FCγRIII in NK cells and critical for ADCC in the I3C group (p<0.05 for all). Our results show that I3C modulates NK cell functions to promote ADCC, suggesting its potential as an adjuvant in HIV vaccines to improve efficacy.
Enhance HIV Vaccine Efficacy by Mucosal Adjuvant: Unraveling Aryl Hydrocarbon Receptor Agonists in Boosting Antiviral NK Cell Responses in Prophylactic HIV Vaccines.
Category
Poster and Podium (Block Symposium)