Live SIV vaccine correlate of protection: local antibody production and concentration on the path of virus entry

We sought design principles for a vaccine to prevent HIV transmission to women by identifying correlates of protection conferred by a highly effective live attenuated SIV vaccine in the rhesus macaque animal model. We show that SIVmac239Δnef vaccination recruits plasma cells and induces ectopic lymphoid follicle formation beneath the mucosal epithelium in the rhesus macaque female reproductive tract. The plasma cells and ectopic follicles produce IgG antibodies reactive with viral envelope glycoprotein gp41 trimers, and these antibodies are concentrated on the path of virus entry by the neonatal Fc receptor (FcRn) in cervical reserve epithelium and in vaginal epithelium. This local antibody production and delivery system correlated spatially and temporally with the maturation of local protection against high dose pathogenic SIV vaginal challenge. Thus, designing vaccines to elicit production and concentration of antibodies at mucosal frontlines could aid development of an effective vaccine to protect women against HIV-1.