The National Institutes of Allergy and Infectious Diseases has announced a new funding opportunity to support the development of computational models and immunologic studies that will advance our understanding of the requirements for improving anti-influenza immunity, including inducing broad immune protection, and enhancing immune durability that will inform design of universal or improved seasonal flu vaccines.
Seasonal influenza epidemics, caused by influenza A and B viruses, result in 3–5 million severe cases and 300,000–500,000 deaths globally each year. The burden of influenza can vary widely between seasons, in part due to characteristics of the circulating viruses, the existing immunity in the population, and the effectiveness of seasonal influenza vaccines against the circulating virus strains.
The generation of broad protective immunity to natural influenza infection or vaccination requires a coordinated, carefully regulated series of events involving a variety of cell types. Computational modeling methods can deepen our understanding of this dynamic system, as they have already provided novel insights into various aspects of immune system function, including: antibody production and maturation/somatic mutation, T cell activation, T cell development and differentiation, generation and maintenance of immunological memory, and host-pathogen interactions.
Projects funded under the initiative are expected to lead to a better understanding of how pre-existing immunity and repeat exposures (natural infection or vaccination) shape an individual’s immune “landscape.” Predictive modeling of adjuvants and vaccine formulations and experimental validation supported through this program also can enhance host immune responses and provide foundational information for further development of universal and improved seasonal influenza vaccines.
Projects must focus on human studies. Immunologic analyses using appropriate animal models are also permitted, where the animal studies will complement the human immunology studies and enhance computational model refinement.
This initiative will support iterative computational and immunologic research on topics such as, but not limited to:
- Identification of the host immune parameters of response/non-response to existing or novel seasonal influenza vaccine formulations and/or candidate universal influenza vaccines.
- Elucidation of required immunologic parameters, beyond neutralization antibodies to viral hemagglutinin, that lead to protective immunity and can serve as correlates of protection to foster development of effective seasonal or universal influenza vaccines.
- Determination of how pre-existing immunity and repeat exposures (natural infection and/or vaccines) shape an individual’s immune “landscape” and affect vaccine efficacy.
- Examination of the role of adjuvants/vaccine formulations in improving host responses and long-lived immunity, including in healthy individuals across the lifespan (infants, children, adults, and older adults), and immunocompromised populations.
In addition to computational models, applicants may propose the development and/or refinement of bioinformatic (data analysis) tools, but only as necessary for completion of the proposed studies, not as the focus of the application. Data-mining software that retrieves data from databases may be incorporated into proposals but should not be the focus of the application.
This funding opportunity supports the NIAID Universal Influenza Vaccine Strategic Plan. This initiative combines computational approaches and experimental techniques, with a wealth of existing data and clinical samples to create an opportunity for significant progress in developing and validating computational models of immunity to both influenza infection and vaccination. Such models and biologic insights will support further development of universal or improved seasonal influenza vaccines.
Computational Models of Influenza Immunity (U01 Clinical Trial Not Allowed). National Institutes of Allergy and Infectious Diseases (NIAID). Notice of Funding Opportunity Number (NOFO): RFA-AI-23-056. Expiration Date: 27 Jan 2024.