Strategies for Controlled Release of HIV Vaccines (SCORE-H) (R01 Clinical Trial Not Allowed)

Notice of Funding Opportunity Description Background Although vaccines are among the most effective approaches to control viral diseases, developing a prophylactic or therapeutic HIV vaccine has proven elusive. There are no licensed vaccines for HIV. Strategies for induction of HIV broadly neutralizing antibodies will likely require repeated exposures over long periods, including immunization with distinct antigens in sequential order. Such immunization strategies will require development of technologies for controlled vaccine release. Recent advances in materials-based science, controlled release technologies, delivery systems, and immunology provide opportunities to enhance the quality, potency and durability of vaccine-induced T cell and antibody responses to HIV-1. Materials-based approaches can be engineered to improve the stability, spatiotemporal release, and presentation of multiple vaccine components; for example, by controlling the time frame and dose of vaccine delivery over days to weeks. Recent studies have shown that a slow-release vaccine is superior to bolus administration at inducing breadth, potency, and durability of antibody responses to HIV antigens by prolonging antigen exposure in the germinal centers, thereby enhancing the maturation of B cells and generating stronger humoral immune responses. Further research is needed to elucidate the mechanisms underlying the immunological improvements observed with slow-release vaccine delivery and to translate such concepts into clinical application. It will be crucial to determine how the duration of exposure to vaccine components impacts immune cell biology, and how to calibrate vaccine release to improve responses while avoiding immune exhaustion and over-activation. Advancing safe, effective, and well-tolerated controlled release vaccines is an unmet need that may enhance vaccine effectiveness and practicality, leading to better adherence to complex regimens, fewer adverse reactions, and cost savings. Finally, iterative behavioral studies during product development to determine vaccine/provider product expectation/preferences are critical to facilitate product uptake and use.