Background: Increasing evidence suggest that HIV can be controlled by Natural Killer cells (NK cells), via multiple mechanisms including antibody dependent cellular cytotoxicity (ADCC). In the RV144 vaccine trial, that showed 31% protection from HIV acquisition, there was an inverse correlation between risk of infection and ADCC, suggesting the importance of NK cells. NKG2A+ NK cells express CD16 and mediate ADCC. Mucosal NKp44+ NK cells produce IL-17 and IL-22 are important for the homeostasis of mucosal compartments. Here we investigated whether the ALVAC/SIV gp120 vaccine regimen adjuvanted with ALUM or MF59 could affect vaccine efficacy and NK cell function in mucosa. Methodology: Two macaque cohorts were vaccinated with ALVAC-SIV gp120 vaccines. One group was boosted with the gp120 protein, adjuvanted with ALUM (n=27) while the other group was given the gp120 formulated with MF59 (n=27). All the animals were challenged with low repeated dose of SIVmac251 intra-rectally. Rectal biopsies were analyzed at one week after the last immunization for the frequency and function of NK cells by flow cytometry. Results: We observed a significant protection from SIVmac251 acquisition versus the 47 control animals in the ALUM but not in the MF59 group. Both vaccines recruited NKG2A+ and NKp44+ NK cells to the gut. However, the frequency of NKG2A+CD107a+ NK cells and NKG2A+TNFα+ NK cells were significantly higher in the MF59 group (p=0.015, P=0.0468) following stimulated with PMA/Ionomycin whereas the NKp44+IL17+ NK cells were significantly higher in the ALUM group when stimulated with SIV env peptides (p=0.0098). Conclusions: Our results indicate that vaccination with ALUM recruits regulatory NKp44+IL17+ NK cells whereas vaccination with MF59 was associated with a higher recruitment of cytotoxic NKG2A+CD107+ NK cell subsets to the gut. However, none of the differences correlated with protection from SIV mac251 acquisition.
CROI Conference
