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Immune Mechanisms for Disease Prevention
When beginning your next investigator-initiated application, consider the following NIH highlighted topic. The area of science described below is of interest to the listed NIH Institutes, Centers, and Offices (ICOs). This is not a notice of funding opportunity (NOFO).
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Topic Description
Post Date: August 17, 2026
Expiration Date: August 17, 2028
Purpose
This topic encourages applicants to accelerate research on immune-based mechanisms for disease prevention.
Background
Immune-based approaches that leverage the body’s immune system may help in preventing various infectious diseases, chronic illnesses such as cancer, autoimmune disorders, and allergic conditions. It does this through physical barriers, innate and adaptive immune responses, and regulatory mechanisms that maintain immune balance. Immune-based prevention strategies (immunoprevention) work by strengthening, directing, or modulating these mechanism-based defenses before disease develops. Major approaches include active immunization through vaccines, passive immunity through monoclonal antibodies, disease prevention using immune-modulating agents, and lifestyle measures that support immune health. Immunoprevention focuses on maintaining or improving immune health in healthy people or those at high risk of disease, with the goal of preventing disease onset. The terms immunoprevention and immunoprophylaxis are largely interchangeable, both referring to immunological methods used to stop disease before it occurs.
Immunoprevention can involve both broad immune-enhancing interventions and specific tools such as immunomodulator agents, vaccines, and adjuvants. A major challenge in immunoprevention is that preventive agents must be safe, minimally toxic, and capable of providing long-term protection, since they are often given to relatively healthy individuals at elevated risk. Recent proof-of-principle preclinical studies show that preventive vaccines and related immune interventions can successfully stimulate host immune responses, supporting the promise of immunoprevention in populations with defined disease risks.
High priority research topics to advance immune-based mechanistic approaches for disease prevention include but are not limited to:
- Study early immune changes in disease development. Investigate novel immune pathways, early disease pathogenesis, microenvironment changes, and immune alterations that drive disease initiation.
- Develop and test immunopreventive strategies. Advance preclinical research on preventive agents, vaccines, vaccine platforms, formulations, and adjuvants for disease prevention.
- Understand mechanisms of immune-based prevention. Explore how vaccines and immunomodulatory agents work, including immune surveillance, immunoediting, inflammatory modulation, innate signaling, and epigenetic changes.
- Build better models and evaluate drug effects. Develop and optimize relevant preclinical, computational, mathematical, and/or human relevant models, while characterizing the immune effects of drugs in early-stage disease settings.
- Design prevention vaccines for high-risk groups. Support (neo)antigen discovery, vaccine development for precancerous and progressive disease stages, and evaluation of vaccine efficacy, toxicity, and autoimmunity in high-risk populations.
Lillian Kuo, Ph.D. (Division of Cancer Biology)
[email protected]
Altaf Mohammed, Ph.D. (Division of Cancer Prevention)
[email protected]
Participating ICOs
Immune-based approaches for cancer prevention and interception use the immune system to detect and destroy precancerous cells/lesions before they progress into invasive cancers. The overarching scientific research objectives are to encourage immunoprevention and/or immuno-interception cancer research. Research may include:
- Studies focused on understanding basic immune mechanisms and pathways of immunoprevention and the discovery and development of translational immunoprevention strategies.
- Studies investigating immune cells from early neoplastic lesion development to initial progression into a clinically detectable tumor.
- Research on immunoprevention approaches that interrogate mechanisms of action, evaluate efficacy, and investigate neoantigens and/or targets in the highest risk populations (e.g., inherited cancer predisposition, individuals with precancers or exposed to environmental carcinogens, cancer survivorship cohorts, etc.) for the development of immune interventions.
Altaf Mohammed, Ph.D. (Division of Cancer Prevention)
[email protected]
Lillian Kuo, Ph.D. (Division of Cancer Biology)
[email protected]
NCCIH supports research that elucidates how complementary and integrative health (CIH) approaches prevent disease through immune-based mechanisms within a whole person health research framework. CIH approaches include natural products (e.g., dietary supplements, botanicals, probiotics) and mind-body interventions (e.g., meditation, hypnosis, acupuncture). Whole Person Health research examines the impact of multicomponent interventions on multiple organs or systems at the individual, behavioral, social, and environmental levels to promote health, well-being, resilience, chronic pain, chronic disease prevention, and health restoration,
Priorities include:
• Mechanisms on how CIH interventions modulate immuno-preventive outcomes across multiple, interconnected organ systems.
• Identifying optimal dosing and timing of CIH interventions to reduce disease risk.
Hye-Sook Kim, PhD
[email protected]
NIA supports the development of immune-based approaches to rejuvenate the aged immune system; prevent development of aging-related diseases; or enhance healthspan and lifespan. Examples of research areas relevant to NIA may include, but are not limited to:
- Elucidation of the mechanisms of immune aging and its impact on immunoprevention in aging.
- Characterization of the mechanism, biomarkers, and potential therapeutic targets responsible for aging-related susceptibility to infections.
- Research on prophylactic treatment (vaccines, therapeutics) that would target brain proteinopathies, modulate neuroinflammation, or explore emerging evidence that suggests that certain vaccines (influenza, herpes zoster) may be associated with dementia risk.
- Development of immunological and pharmacological agents to slow or reverse age-related decline in immune function (immunosenescence) that drive incidence and severity of age-related diseases.
Mulualem Tilahun, Ph.D., D.V.M.
[email protected]
Maja Maric, Ph.D.
[email protected]
Examples of research areas relevant to NIAID:
- Studies into the basic immune mechanisms associated with susceptibility (risk factors) versus/or resistance to infection, persistence of infectious agents, or immune-mediated diseases, including the impact of intrinsic (e.g., age, genetics, microbiome) or extrinsic (e.g., prior infections, vaccines, environmental exposures) factors on immune health status
- Development and testing of novel vaccine strategies to prevent infectious or immune-mediated diseases (e.g., allergy, asthma, autoimmunity)
- Discovery and development of novel classes of vaccine adjuvants that selectively promote immune profiles associated with protective immunity against infectious diseases
- Development of prophylactic antibodies or other biologics/drugs to prevent infectious or immune-mediated diseases (e.g., autoimmunity, allergy, asthma)
Wolfgang Leitner, MSC Ph.D.
[email protected]
Immune-based approaches for prevention and interception of NIAMS-relevant diseases use the immune system to maintain tissue homeostasis, prevent loss of tolerance, and block early inflammatory or autoimmune processes before they progress into clinically manifest rheumatic, skin, or musculoskeletal diseases and conditions. NIAMS encourages mechanistic, translational and clinical research in immunoprevention and/or immune-based interception across NIAMS mission areas.
Research may include:
• Mechanistic studies of early immune dysregulation in autoimmune rheumatic diseases, inflammatory skin diseases, or musculoskeletal conditions with an immune component.
• Preclinical development of tolerogenic vaccines or immune-modulating agents aimed at preventing transition from preclinical autoimmunity or subclinical inflammation to overt disease.
• Development of joint, skin, bone, or muscle organoid systems incorporating immune cells to test immunopreventive interventions.
Marie Mancini, PhD
[email protected]
Research is needed to define immune mechanisms of prevention at the central nervous system (CNS)–peripheral interface during the earliest stages of acute and repeated exposure to substances of misuse. This work can advance immune-based approaches to prevent substance-related CNS injury and dysfunction.
Related topics include:
• Studies of CNS–peripheral immune signaling and crosstalk during exposure and early pathogenesis;
• Early immune and microenvironmental changes, including immune surveillance, inflammatory modulation, and immune signaling, that precede maladaptive responses or CNS injury;
• Substance-induced bidirectional communication and feedback loops among CNS-resident, CNS border-associated, and recruited peripheral immune cells across brain, barrier, vascular, and peripheral compartments;
• Mechanisms by which immunomodulators alter CNS–peripheral crosstalk, including innate signaling and epigenetic changes, to limit injury and persistent dysfunction and promote repair.
Kiran Vemuri, Ph.D.
[email protected]
NIDCR encourages the development of immune-based approaches to prevent periodontitis, oral cavity infections including HIV and HPV, oral complications arising from chronic inflammation and autoimmune diseases, and oral pathogen–driven precancerous and cancerous lesions in the oral cavity and oropharynx. Research may include:
- Elucidating mechanisms of oral mucosal immunity, innate and adaptive immune responses, and regulatory mechanisms that maintain immune homeostasis.
- Developing immunoprevention strategies utilizing dental and oral tissue specific mechanisms, towards translational immunoprevention treatment strategies.
- Preventing early disease onset, including approaches to block the transition from acute to chronic inflammation.
- Developing novel platforms and methodologies to advance immunoprevention strategies. Elucidating the role of the immune system in maintaining oral microbiome homeostasis and preventing a shift to dysbiosis.
Preethi Chander, PhD
[email protected]
The Office of Research on Women’s Health (ORWH) is interested in projects that:
- Examine sex-specific biology and women-relevant outcomes, including study designs and analyses in disease prevention studies.
- Harness computational models to investigate sex differences.
The Office of Autoimmune Disease Research in ORWH (OADR-ORWH) is interested in:
- Research focused on early immune changes in the prodromal phase of autoimmunity.
- Immunopreventative strategies for autoimmune diseases.
- Utilizing federated data platforms to enhance pattern recognition in complex multiomic datasets, enabling deeper insights into, autoimmune disease pathogenesis, co‑occurring autoimmune diseases and shared pathogenic pathways.
- Harnessing computational models to optimize clinical trial design, including use of digital twins and synthetic control arms and leveraging existing and new clinical trial and registry data to advance immune mechanisms for disease prevention in autoimmunity.
Rajeev Agarwal, Ph.D.
[email protected]
Victoria Shanmugam, MBBS, MRCP, FACR, CCD
[email protected]
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