Atomic layer deposition for core-shell microparticle vaccines enabling programmable antigen delivery to lymph nodes enhance humoral immune responses

Technologies that simplify complex dosing regimens as single-shot immunizations may be important for vaccines against difficult to neutralize pathogens. Here we characterized delivery mechanism of clinically-relevant HIV vaccine immunogens using core-shell microparticles comprising immunogen formulations spray-dried to form solid spherical microparticles and subsequently coated with a nanoscopic alumina shell using atomic layer deposition (ALD). ALD particles exhibited a time delay in antigen release programmed by the alumina shell followed by prolonged antigen release, which steadily accumulated in antigen-presenting cells at the injection site and draining lymph nodes and accumulated on follicular dendritic cells in B cell follicles. ALD vaccines elicited continuous expansion of antigen-specific germinal center B cells over 8 weeks, serum antibody responses with >10-fold slower antigen-binding off-rates, and 2-fold more long-lived plasma cells compared to traditional bolus vaccination with potent adjuvants. Single administration ALD technology thus promotes key events in the primary immune response important for vaccines against HIV and other challenging pathogens.