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Rewilding Immunology: Response profiles and side effects of immunization in natural vs. controlled genetic backgrounds

Award Number: R15AI203529
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/15/2026
PERIOD OF PERFORMANCE END DATE: 06/30/2029

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Rewilding Immunology: Response profiles and side effects of immunization in natural vs. controlled genetic backgrounds - PROJECT SUMMARY The lab mouse has been used almost exclusively as the model for developing and testing nanoparticle (NP) formulations for DNA/mRNA vaccine delivery. The problem: Only about 10% of NP treatments and vaccinations are successful in clinical trials. Nanomedicine, immunological, and vaccine development studies commonly rely on inbred mice kept in specific pathogen-free facilities. As a result, the magnitude and individual variation in the responses of lab mice to immune challenges is low. Humans display immune responses that are higher in magnitude and highly variable due to genetic variation among individuals and exposure to diverse microbial environments. This difference between lab mice and humans contributes to poor translation of mouse to human outcomes. The solution: The use of an immunologically robust and genetically variable model would allow researchers to evaluate how a diverse population responds to their product before clinical trials. Studies comparing the baseline and vaccine-induced immune responses of inbred lab and wild house mice have consistently shown that the immune responses of lab mice are substantially lower than those of wild mice. Further, the range and diversity of immune responses observed in wild house mice mimic humans more closely than inbred lab mice. While wild house mice can be challenging to collect, and they carry pathogens that can alter immunological responses and put animals in other studies at risk, wild-derived mice could serve as a valuable supplement to lab mice for NP vaccine research. Our approach: By comparing wild-derived house mice, and lab mice, we will determine if the baseline and stimulated immune responses of wild-derived house mice are similar to published data on wild mice and humans, and greater than lab mice. Further, we will evaluate the responses of the same populations of mice to an mRNA vaccine that includes a model mRNA carried by a well-characterize lipid nanoparticle and a novel nanoparticle to determine if the wild-derives mouse has an immunological memory that is greater than lab mice. Undergraduate student involvement: We estimate that 48 undergraduates will be involved in this project, 24 research assistants who will receive credit to monitor the live mice and help with vaccinations and tissue collection, and four undergraduates will be awarded full-time summer positions each year to participate in lab work. Finally, 20 undergraduates from T. Schwartz’s Functional Genomics class (20 U) will complete the transcriptomics analysis.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $439,335 )
2026	2026	AUBURN UNIVERSITY	321-A INGRAM HALL	AUBURN	AL	36849	LEE	USA	Allergy and Infectious Diseases Research	000	1	7/15/2026	NEW	$439,335
														Subtotal = $439,335

Grand Total All Awards = $439,335

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Rewilding Immunology: Response profiles and side effects of immunization in natural vs. controlled genetic backgrounds

Award Number: R15AI203529

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 07/15/2026

PERIOD OF PERFORMANCE END DATE: 06/30/2029

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