Funding Opportunity Number: RFA-AI-25-006
Deadline: June 10, 2025
Research Objectives
This program supports research to define the molecular and immunological mechanisms triggered by adjuvant combinations leading to long-term protective immunity against infectious diseases. Studies must explore the mechanism(s) of action (MOA) of combination adjuvants that have already been shown individually to be effective in enhancing or modulating immune responses when compared with antigen alone (*i.e.*, model antigens, pathogen-derived molecules, or vaccine components). At least one adjuvant combination must be proposed for examination, but additional combinations also are allowed. Applicants should include a strong rationale for combining adjuvants based on what is known about their individual immunostimulatory properties and/or effects in previously studied vaccines. Adjuvant combinations that include non-Toll-like receptor (TLR) agonists are of particular interest.
Other requirements of the program include: 1) examination of immune mechanisms in animal models; and 2) if standard inbred and germ-free mouse models are used, validation in more complex model systems (*e.g.*, Collaborative Cross mice, microbial experienced (“dirty”) mice, humanized mice, other relevant animal models*, in vitro* human models, etc.) to demonstrate translatability toward human use. The mechanisms explored may include, but are not limited to, stimulation of multiple immune receptors, or activation of multiple signaling pathways in animal models or in in vitro systems. Use of in vitro systems is allowed and inclusion of human samples (primary cells, tissue samples, and/or cell lines) is encouraged.
MOA studies may include, but are not limited to:
- Quantitative and qualitative assessments of antibody production, avidity, and function
- CD4 and CD8 T cell activation and function
- Induction and maintenance of innate and adaptive immune memory
- Tissue-specific immunity
- Studies of signaling pathways and cascades
- Characterization of innate immunity including, but not limited to, studies of dendritic cells, macrophages, NK cells, innate lymphoid cells, neutrophils, and complement
- Pathogen challenge studies showing protective efficacy or mitigation of disease
- Systems immunology analyses
- Safety studies, such as measurement of serum levels of proinflammatory cytokines or determination of weight loss, fever, or tissue damage to demonstrate improved immunogenicity without increased reactogenicity
- Determination of correlates of immunity
- Use of computational/mathematical modeling to examine MOA and synergistic effects (must include experimental validation)
For more information, please see the opportunity webpage.