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 Abs reactive with viral envelope glycoprotein gp41 trimers, and these Abs are concentrated on the path of virus entry by the neonatal FcR in cervical reserve epithelium and in vaginal epithelium. This local Ab 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 Abs at mucosal frontlines could aid in the development of an effective vaccine to protect women against HIV-1.
Bibliographical noteFunding Information:
This work was supported by a grant from the International AIDS Vaccine Initiative (to A.T.H.); National Institutes of Health Grants AI 086922 (to A.T.H.), AI 071306 and RR00168 (to R.P.J.), AI095985 (to R.P.J. and A.T.H.), and AI 055332 and 1UM1AI100663 (to D.R.B.); a Center for HIV/AIDS Vaccine Immunology/HIV Vaccine Trials Network Early Stage Investigator award and Grant U19 AI 067854 (to R.K.R.); a Ragon Fellowship (to J.E.V.); and by federal funds from the National Cancer Institute, National Institutes of Health under Contract HHSN261200800001E and the National Institutes of Health/National Institute of Allergy and Infectious Diseases Reagent Resource Support Program for AIDS Vaccine Development, Quality Biological, Inc., Gaithersburg, MD (National Institute of Allergy and Infectious Diseases Division of AIDS Contract HHSN272201100023C).