Nanoparticle vaccines enhance humoral responses to a malaria antigen by expanding Tfh cells and inducing germinal center formation (166.10)

Abstract

Abstract Nanoparticles (NP) are promising delivery vehicles for vaccines that promote humoral and cellular immunity in concert. We recently developed a novel lipid-based NP vaccine system, termed interbilayer-crosslinked multilamellar vesicles (ICMVs). ICMVs efficiently entrap and co-deliver antigens and molecular adjuvants to lymphoid tissues, initiating potent cellular and humoral immune responses. ICMVs were synthesized by fusing liposomes containing antigen into multilamellar vesicles, followed by bilayer-to-bilayer crosslinking of lipid bilayers within the vesicle walls to stabilize the particles. ICMVs carrying ovalbumin and the TLR agonist MPLA induced robust cytotoxic T lymphocyte responses in mice, achieving a peak ~30% tetramer+ cells in the CD8+ T-cell population after 3 immunizations. Mice vaccinated with ICMVs containing a candidate Plasmodium vivax antigen raised high-titer, high-avidity antibody responses against the antigen lasting > 1 yr, at 10-fold lower dose of antigen than conventional adjuvants such as alum or Montanide. Compared to vaccination with alum, immunization with ICMVs prolonged antigen accumulation at the draining lymph nodes, enhanced germinal center formation, and increased the expansion of antigen-specific follicular helper T-cells, partially explaining the enhanced antibody response. These results suggest that antigen/adjuvant-carrying ICMVs may serve as a platform to elicit potent cellular and humoral immune responses against infectious pathogens.