Through Notice of Special Interest (NOSI): Leveraging Microbial Exposure for Improving Mouse Models of Human Immunity, NIAID is interested in research to characterize immune system development, regulation, and function in mouse models to advance understanding of human immune status and function during homeostasis or in infectious or immune-mediated diseases (e.g., allergy, autoimmunity, transplant rejection).
Mouse models are critical in the study of immune system development and function, microbial pathogenesis, and allergic and autoimmune diseases. They have provided mechanistic insights that have been foundational for the development of therapeutics and vaccines. Despite these advances, multiple discrepancies in immune responses between laboratory mice and humans have limited the models’ utility for predicting human responses to candidate vaccines and immunotherapies. The use of “dirty mice,” that is, mice with diverse microbial experience that can more closely model the human immunological system than laboratory mice living in controlled specific pathogen free (SPF) facilities, could recapitulate immune responses to vaccines and immunotherapy seen in human clinical trials.
Currently, mice with diverse microbial experience are underused by the immunology community due to increased animal husbandry and housing costs. This NOSI aims to advance our understanding of the impact of a host’s microbial experience on the development and function of host immunity and provide the data necessary to encourage broader use of the mouse models in immunologic and microbiologic research.
NIAID Research Areas of Interest
A comparison of microbially diverse dirty mice with those maintained under standard SPF conditions shows that SPF mice poorly recapitulate mature human immune responses and exhibit immune responses similar to a human newborn. In contrast, mice with diverse microbial experiences react to stimuli more like human adults and recapitulate immune responses to vaccines and immunotherapeutic seen in human clinical trials.
NIAID is interested in applications that propose studies in the following research approaches:
- Comparing SPF mice to animals with a diverse microbial exposure to assess immune homeostasis or in response to various infectious or immune-mediated diseases.
- In vitro and ex vivo comparative assessment between human primary cells/samples and mice with diverse microbiome exposures, immune profiles, disease status, and/or response to an adjuvant, vaccine, or immune-based therapeutic.
- Evaluating the influence of diverse microbial experiences on immune responses to a pathogen, antigen, adjuvant, vaccine, or therapeutic.
- Assessing the impact of diverse microbiome exposure in early life on immune system maturation and disease development.
- Comparing head-to-head the immune profile and response of microbial experienced mouse colonies established using different approaches.
- Identifying the factors that may affect the mouse’s response to microbial exposure, such as the duration of exposure, sequence of exposure to infectious agents, prior infections, and mouse age, sex, or genetic background.
To further encourage broader use of the mouse models in immunologic and microbiologic research, your project might also include:
- Fundamental immunology: Define the properties, interactions, development, and function of innate and adaptive components (cells, molecules pathways) of the immune system during homeostasis, or in response to pathogenic infections or vaccination.
- Allergic diseases, with a focus on asthma, rhinitis and rhinosinusitis, food allergy, and atopic dermatitis: Determine elements associated with disease, including development and persistence, genetics, identification of targets of new preventive and therapeutic approaches.
- Autoimmunity: Define the immunologic basis of disease, e.g.,
- Develop a greater understanding of the fundamental immunologic principles underlying disease onset and progression.
- Develop improved animal models of disease and diagnostic tools.
- Identify and evaluate more effective immune-based treatment and prevention strategies.
- Transplant immunology: Elucidate immunological mechanisms and pathways that contribute to
- Allograft rejection or tolerance in models of pancreatic islet, solid organ, or vascularized composite allograft transplantation.
- Graft-versus-host disease in models of bone marrow/hematopoietic stem cell transplantation.
- Vaccinology: Develop an understanding of how broad microbial exposure impacts safety, immunogenicity, and efficacy of adjuvants and vaccines.
Application and Submission Information
This notice applies to due dates on or after February 5, 2025, and subsequent receipt dates through November 16, 2027.
To apply to this initiative, use one of the following notices of funding opportunity (NOFOs) or any reissues of these announcements through the expiration date of this notice.
- NIH Research Project Grant (Parent R01, Clinical Trial Not Allowed)
- NIH Exploratory/Developmental Research Project Grant (Parent R21, Clinical Trial Not Allowed)
You should follow all instructions in the SF 424 (R&R) Application Guide and the NOFO you used for submission, with the following addition: Write “NOT-AI-24-078” (without quotation marks) in the Agency Routing Identifier field (box 4B) of the SF 424 R&R form.
For budget and project period limits, refer to the NOFO through which you apply.
Inquiries
Direct all inquiries to NIAID’s scientific/research contact, Dr. Qian Joy Liu, at liujoy@niaid.nih.gov or 301-761-6621.