Abstract
PROBLEM: The capacity of antigen-carrying vaccine nanoparticles (NPs) administered vaginally to stimulate local immune responses may be limited by the relatively low numbers of antigen-presenting cells (APCs) in the genital mucosa. Because inflammation is associated with increased susceptibility to sexually transmitted infections, we sought to increase APC numbers without causing inflammation. METHOD OF STUDY: In this study, we evaluated intravaginal delivery of chemokines, growth factors, or synthetic adjuvants to expand APCs in reproductive tissues. RESULTS: We found that granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulated expansion of CD11b+ dendritic cells (DCs) within 24 hr of intravaginal administration, with no effect on Langerhans cells or macrophages. Expansion of the CD11b+ DC population was not associated with increased inflammatory cytokine production, and these cells retained phagocytic function. CONCLUSION: Our data suggest that non-inflammatory expansion of mucosal APCs by intravaginal GM-CSF could be used as an adjuvanting strategy to potentiate the genital immune response to nanoparticulate mucosal vaccines.