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A novel oral vaccine targeting T cell responses to overcome oral vaccine failure

Award Number: F30AI191651
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 10/05/2026
PERIOD OF PERFORMANCE END DATE: 10/04/2027

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A novel oral vaccine targeting T cell responses to overcome oral vaccine failure - PROJECT SUMMARY This proposal aims to train a DVM-PhD student for a career as a clinician-scientist uniquely prepared to advance the fields of immunology and vaccine development. This project will develop the applicant’s skills in computational biology, in vivo modeling, T cell immunity, vaccine design, grant writing, mentorship, and clinical skills. Rotavirus remains a major cause of morbidity and mortality despite the availability of four attenuated live vaccines. These vaccines exhibit high efficacy in some populations but is much lower in others. Additionally, the safety of attenuated vaccines remains a concern. One cause of oral vaccine failure is environmental enteric dysfunction (EED), a subclinical condition defined by intestinal inflammation, increased mucosal permeability, and aberrant T cell signaling. To address the gap in vaccine efficacy and safety, next generation subunit vaccines and mucosal immune stimulating adjuvants are needed. We have developed a novel probiotic-based vaccine platform using the bacterium Lactobacillus acidophilus. Recombinant Lactobacillus acidophilus (rLA) represents a desirable vaccine delivery platform because it can be engineered to express viral antigens and adjuvants, engages with the mucosal immune system, survives the harsh intestinal tract, can be lyophilized, and delivered orally. T cells play key roles in antiviral immunity through direct cytotoxic killing of infected cells, orchestrating antibody-mediated immunity, and modulating the local immune system through the production of potent cytokines. However, little is known about T cell induction by rLA vaccines despite T cells being the most abundant immune cell in the human small intestine. These studies will determine how T cell immunity is induced by rLA-delivered model peptides and the effects of three novel adjuvant strategies on immune induction. T cells also play a role in the development of vaccine failure in EED, with a regulatory T cell population likely being the primary cause of oral vaccine failure. I hypothesize that rLA vaccines represent a potential tool to overcome EED-related vaccine failure because it induces antigen-specific Th1 immunity to LA- delivered antigens. These studies will utilize a murine model of EED wherein mice will be vaccinated with a novel rLA-based rotavirus vaccine expressing a protective rotavirus epitope and two immune-stimulating adjuvants to test the novel rLA vaccine in a relevant clinical state of vaccine failure. Immunity to the candidate rLA rotavirus vaccine will be compared to the gold standard attenuated rotavirus vaccine which exhibits limited efficacy in many neonates and infants. Antibody-mediated immunity, antigen-specific T cell immunity, and immune cell immunophenotyping will be performed to determine immunologic consequences of the candidate rLA rotavirus vaccine. Overall, these studies aim to improve the efficacy of an rLA-based vaccine platform through mechanistic studies of T cell immunity and in vivo studies using a relevant model of EED.


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 = $43,523 )
2026	2026	COLORADO STATE UNIVERSITY	601 S HOWES ST	FORT COLLINS	CO	80521	LARIMER	USA	Allergy and Infectious Diseases Research	000	1	4/3/2026	NEW	$43,523
														Subtotal = $43,523

Grand Total All Awards = $43,523

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A novel oral vaccine targeting T cell responses to overcome oral vaccine failure

Award Number: F30AI191651

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 10/05/2026

PERIOD OF PERFORMANCE END DATE: 10/04/2027

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