Plasmablast Phenotype and Mucosal Antibodies to V2 in Vaccine-induced Protection Against SIVmac251

OA06.03 Background: We have recently recapitulated the RV144 vaccine efficacy in a SIVmac251 model. In our study, rectal anti-cyclic V2 IgG antibodies correlated with a decrease risk of SIVmac251 acquisition (p=0.0063). Analysis of the homing markers on plasmablast (PB) resulted in a higher frequency of alpha4beta7+ PBs in animals with higher levels of IgG and IgA to cyclic V2 in rectal mucosal. Methods: We investigated the homing potential in 5 different vaccine strategies by measuring alpha4beta7 and CXCR3 as markers for gut mucosa and inflammatory sites, respectively in a total of 118 macaques. The immunoglobulin (Ig) expression on PB and the mucosal antibody responses were assessed in all groups. We studied a cohort of macaques immunized 4 times with ALVAC-SIV and twice with gp120/alum or gp120/MF59. A second cohort was immunized twice with DNA-SIV/gp120/alum or once Ad26-SIV, and boosted with ALVAC-SIV/gp120/alum twice. Finally, an additional group was immunized 4 times with NYVAC-SIV boosted twice with gp120/alum. Results: Both ALVAC-SIV/gp120/alum and DNA-SIV/gp120/alum immunized animals were protected from SIVmac251 mucosal acquisition (p=0.029 and p=0.014, respectively). However, no protection was observed with ALVAC-SIV/gp120/MF59, NYVAC-SIV/gp120/alum and Ad26 primed regimens. DNA-SIV/gp120/alum and ALVAC-SIV/gp120/alum immunizations increased the frequency of alpha4beta7 plasmablasts (p = <0.0001 and p=0.015) while ALVAC-SIV/gp120/MF59, NYVAC-SIV/gp120/alum increased the frequency of CXCR3+plasmablasts (p=0.0001 and p=0.004 respectively). We are completing Ad26-SIV/gp120 and DNA-SIV/gp120/alum studies as well as the analysis of Ig expression and correlations with mucosal antibody responses. Conclusions: Preliminary results suggest that different vaccine modalities are able to alter the plasmablast homing and the effector functions of the antibody response at mucosal sites that may correlate with protection.