Systems Approach to Understand Mechanisms of Heterogeneous Response to Influenza (R01 Clinical Trial Not Allowed) | RFA AI 21 017

Opportunity Information: Apply for RFA AI 21 017

Systems Approach to Understand Mechanisms of Heterogeneous Response to Influenza (R01 Clinical Trial Not Allowed), Funding Opportunity Number RFA-AI-21-017, is a discretionary NIH grant program in the health funding category (CFDA 93.855). The announcement is designed to fund research that explains why people do not respond to influenza infection or influenza vaccination in the same way, with a specific emphasis on using a systems-level perspective and modern computational approaches. In practical terms, the goal is to move beyond one-size-fits-all explanations of immunity and instead identify the biological and mechanistic reasons that some individuals develop strong protective immunity, others have weaker or short-lived responses, and some may experience different clinical or immunological outcomes after exposure to influenza viruses or after receiving influenza vaccines.

A central feature of this opportunity is the expectation that applicants will develop and/or apply computational tools to uncover mechanisms that drive heterogeneity across individuals or groups. This typically implies work that integrates complex, multi-dimensional data (for example, immune profiling data, transcriptomic or other “omics” data, host genetic or epigenetic information, clinical metadata, prior exposure histories, age-related factors, or vaccine formulation differences) and uses computational modeling, systems immunology, network analyses, machine learning, or other advanced analytic frameworks to identify patterns and causal pathways. The emphasis on “mechanisms” signals that the program is not only looking for descriptive correlations (for example, “this biomarker associates with outcome”) but also for analyses and study designs that can reasonably support mechanistic interpretations, such as identifying pathways, cellular programs, or host factors that plausibly explain divergent responses to infection or vaccination.

The mechanism of support is an R01 research project grant, and the FOA explicitly states “Clinical Trial Not Allowed,” meaning the funded projects should not include a prospective clinical trial in which participants are assigned to an intervention to evaluate health-related outcomes. Research can still involve human data, existing cohorts, secondary analyses, observational studies, and use of previously collected clinical or immunological datasets, as long as the work does not cross the NIH definition of a clinical trial under this FOA. Applicants would generally be expected to align their approach with NIH policies on human subjects research, data sharing, and rigor and reproducibility, particularly because computational work often depends on careful handling of confounders, batch effects, missingness, and generalizability across populations and settings.

Eligibility is broad and includes many types of U.S. and non-U.S. organizations. Eligible applicants listed include state, county, and local governments; special district governments; independent school districts; public and state-controlled institutions of higher education; private institutions of higher education; federally recognized Native American tribal governments; Native American tribal organizations other than federally recognized tribal governments; public housing authorities/Indian housing authorities; nonprofits with or without 501(c)(3) status (other than institutions of higher education); for-profit organizations other than small businesses; small businesses; and other entities. The FOA also highlights additional eligible applicant categories such as Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISIs), Hispanic-serving Institutions, Historically Black Colleges and Universities (HBCUs), Tribally Controlled Colleges and Universities (TCCUs), faith-based or community-based organizations, eligible federal agencies, regional organizations, U.S. territories or possessions, and non-domestic (non-U.S.) entities (foreign organizations). This broad eligibility reflects an interest in drawing on diverse research teams, data resources, and population perspectives that can strengthen understanding of heterogeneous influenza responses across different communities.

Key administrative details from the source record include an original closing date of 2021-09-08 and a creation date of 2021-04-27. The listing does not provide an award ceiling or expected number of awards in the provided fields, so those specifics would typically need to be confirmed in the full FOA text on NIH/Grants.gov or the NIH Guide. Overall, the opportunity is best viewed as supporting systems immunology and computationally driven influenza research that can explain variability in immune protection and disease outcomes, with the longer-term public health aim of improving influenza vaccine strategies, predicting who is most at risk, and guiding more targeted or effective interventions without funding new clinical trials under this particular announcement.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Systems Approach to Understand Mechanisms of Heterogeneous Response to Influenza (R01 Clinical Trial Not Allowed)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.855.
• This funding opportunity was created on 2021-04-27.
• Applicants must submit their applications by 2021-09-08. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• Eligible applicants include: State governments, County governments, City or township governments, Special district governments, Independent school districts, Public and State controlled institutions of higher education, Native American tribal governments (Federally recognized), Public housing authorities/Indian housing authorities, Native American tribal organizations (other than Federally recognized tribal governments), Nonprofits having a 501 (c) (3) status with the IRS, other than institutions of higher education, Nonprofits that do not have a 501 (c) (3) status with the IRS, other than institutions of higher education, Private institutions of higher education, For-profit organizations other than small businesses, Small businesses, Others.

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