Host Targeted Interventions as Therapeutics for Infectious Diseases (R21/R33) | Apply Online

Opportunity Summary:

The Host Targeted Interventions as Therapeutics for Infectious Diseases (R21/R33) funding opportunity (RFA-AI-11-032) was a National Institutes of Health initiative, administered through the National Institute of Allergy and Infectious Diseases (NIAID), aimed at accelerating new therapeutic concepts for serious infectious disease threats. Instead of focusing on drugs that directly attack a microbe or virus, this program emphasized the discovery and early development of countermeasures that work by targeting host-encoded functions, meaning normal human (or animal) biological pathways that pathogens rely on to infect cells, replicate, spread within the body, or cause disease. The underlying idea is that if a pathogen depends on certain host processes to complete its life cycle or to trigger damaging inflammation, then carefully designed interventions that modulate those host processes could reduce illness, improve outcomes, and potentially make it harder for pathogens to develop resistance compared with traditional pathogen-targeted drugs.

A key scientific focus of the announcement was the set of “NIAID Category A, B, or C priority pathogens,” which generally includes high-concern agents associated with biodefense and emerging infectious disease risk. By tying the research scope to these priority categories, the opportunity was positioned to support work that could have public health and national security relevance, including diseases where there is limited treatment availability, a high consequence of outbreaks, or meaningful concern about intentional release. The program’s goal language stressed innovation and stimulation of the pipeline, signaling interest in novel targets, mechanisms, and approaches rather than incremental variations of existing antimicrobial strategies.

The mechanism paired an R21 with an R33, which is typically used to support a two-phase project that starts with exploratory, high-impact feasibility work and, if predefined milestones are met, transitions into a second phase aimed at more advanced development. In practice, this structure is often used when the funder wants to encourage bold ideas while still requiring a clear development plan and measurable progress. The R21 phase is commonly used to establish proof-of-concept: identifying and validating a host target, demonstrating that modulating it can block infection or reduce pathogenesis, and generating early evidence of activity in relevant models. The subsequent R33 phase is designed for expansion and maturation of the effort, such as optimization of lead molecules or biologics, deeper mechanistic studies, improved efficacy testing, and other steps that move a concept closer to a credible therapeutic candidate. The combined structure also implies that applicants were expected to define milestones that would justify the transition between phases.

From an applicant standpoint, the opportunity was broadly open to many organizational types. Eligible applicants included public and private institutions of higher education, nonprofit organizations (including those with and without 501(c)(3) status), small businesses, for-profit organizations (including those other than small businesses), and multiple levels of government such as state, county, city, township, and special district governments. It also welcomed a wide range of mission-driven and community-centered institutions, including historically Black colleges and universities, Hispanic-serving institutions, tribally controlled colleges and universities, Alaska Native and Native Hawaiian serving institutions, and faith-based or community-based organizations. Importantly, foreign institutions were eligible, and non-U.S. components of U.S. organizations could apply, which broadened the pool to include international expertise and cross-border collaborations that can be especially valuable for infectious disease research.

Administratively, the program was categorized as a discretionary grant within the NIH health funding activity area, associated with CFDA numbers 93.855 (Allergy and Infectious Diseases Research) and 93.856 (Microbiology and Infectious Diseases Research). It did not require cost sharing or matching funds, which typically lowers barriers to participation and can make it easier for academic groups, nonprofits, and smaller entities to propose ambitious work. The opportunity was posted and created on July 19, 2011, with an original and current closing date of November 30, 2011, and it was archived on December 31, 2011, meaning it was time-limited and is no longer open under that specific announcement.

In terms of overall scale, the announcement listed an estimated total funding amount of $4,000,000. While that figure reflects program-level expectations rather than a guaranteed award level for any single project, it indicates the government’s intent to support a modest portfolio of projects capable of generating tangible movement toward host-directed therapeutics. Because host-targeted strategies can range from small-molecule inhibitors and biologics to pathway modulators and repurposed drugs, the solicitation was positioned to support diverse therapeutic modalities as long as the central premise remained host-function targeting for pathogens of high priority to NIAID.

For applicants seeking the official details at the time, NIH provided an additional information link to the full announcement on the NIH grants guide site. NIH also listed general support contacts through the NIH Office of Extramural Research webmaster for technical issues accessing or linking to the funding announcement, reflecting the standard administrative support structure for NIH FOAs.

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