Impact of Initial Influenza Exposure on Immunity in Infants (U01 Clinical Trial Not Allowed)

The National Institutes of Health (NIH), under the U.S. Department of Health and Human Services, has reissued its funding opportunity titled “Impact of Initial Influenza Exposure on Immunity in Infants” (RFA-AI-27-019). This initiative is spearheaded by the National Institute of Allergy and Infectious Diseases (NIAID) and aims to deepen scientific understanding of how initial influenza exposures—either through natural infection or vaccination—affect long-term immunity in infants and young children. By supporting longitudinal cohort studies, the program intends to advance knowledge essential for designing a universal influenza vaccine that confers robust, durable protection against seasonal and novel strains of the virus. The research seeks to answer pivotal questions surrounding immune imprinting, particularly how the earliest encounters with influenza antigens influence humoral, T-cell mediated, and innate immune responses to subsequent exposures. Infants will be enrolled from birth or prior to first influenza exposure and monitored over at least three flu seasons. Studies will compare immune responses triggered by natural infection versus vaccination and examine how maternal immunity—transferred during pregnancy and breastfeeding—affects the child’s responses. Domestic and international cohorts are eligible, particularly those whose exposure patterns complement those in the United States. Inclusion of pregnant and postpartum mothers is strongly encouraged to better contextualize maternal-infant immunological interactions. Applications are required to propose well-structured, multi-disciplinary cohort studies with detailed data collection and immune profiling. Funded projects must involve dedicated teams: an Administrative and Leadership Team for oversight and communication; a Data Stewardship and Analysis Team for rigorous data and biospecimen management; and a Clinical Research Support Team to ensure regulatory compliance and enrollment success. Data must be shared via public portals such as ImmPort and GenBank, and biospecimens must be accessible for continued research in accordance with NIH policies. Successful applicants may receive up to $3 million annually in direct costs for up to five years. NIAID expects to fund 2–4 awards, with a total FY2027 program budget of $9.6 million. Projects must exclude clinical trials, animal studies, GWAS, behavioral research, and any studies focused on HIV/AIDS. A mandatory Opportunity Fund, starting in the second year, must allocate a minimum of $100,000 annually to support collaborative pilot projects, early-career researchers, or emergent topics consistent with program goals. Applications open on May 4, 2026, and are due by June 4, 2026, at 5:00 PM local time. Applicants are strongly advised to submit early to allow time for error correction. The earliest anticipated start date is March 2027. This program does not require a pre-application such as a letter of intent. While cost-sharing is not mandatory, applicants must adhere strictly to NIH submission and formatting guidelines. Applications must be submitted via NIH’s ASSIST system, Grants.gov Workspace, or through an institutional system-to-system solution. Evaluation will follow NIH’s peer review process, assessing significance, innovation, approach, investigator expertise, and research environment. Particular weight is given to the scientific rigor, feasibility, and the potential to yield findings relevant for developing broadly protective influenza vaccines. An External Advisory Committee will be convened post-award to review progress and advise awardees. Additionally, annual programmatic meetings will serve as forums for collaboration and strategic planning. NIH reserves the right to modify award parameters based on compliance, scientific progress, or agency priorities.

Ensure rigorous cohort design and power analysis; Provide detailed benchmarks; Demonstrate experience with longitudinal cohorts and immunologic studies; Use standardized data collection procedures; Plan for data sharing via ImmPort and GenBank.