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The adventures of Lactobacillus acidophilus: evaluating a recombinant probiotic rotavirus vaccine from host and microbial perspectives

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dc.contributor.authorGilfillan, Darby L., author
dc.contributor.authorVilander, Allison, advisor
dc.contributor.authorDean, Gregg, advisor
dc.contributor.authorAbdo, Zaid, committee member
dc.contributor.authorWilkins, Mike, committee member
dc.date.accessioned2024-09-09T20:52:02Z
dc.date.available2026-08-16
dc.date.issued2024
dc.description.abstractRotavirus is an enteric infection of global importance causing diarrheal-associated illness that can be fatal in young children and the elderly. There is a gap in vaccine efficacy between high- and lower-middle-income countries (LMIC) with LMIC often experiencing diminished vaccine-conferred protection. Rotaviruses, whether attenuated vaccine strains or primary pathogens, do not exist in isolation within the host's gastrointestinal tract. Other actors present within the microbiome can inhibit or augment vaccine efficacy by influencing the vaccine itself or the mucosal immune response. Understanding and exploiting interactions between host and microbe is a promising frontier for mucosal vaccinology. This dissertation will explore the probiotic Lactobacillus acidophilus (LA) as a vaccine platform for a microbiome-minded, next-generation approach to rotavirus immunization. We developed and confirmed a novel recombinant LA (rLA) vaccine expressing rotavirus antigens of the VP8* domain from the rotavirus EDIM VP4 capsid protein along with the adjuvants FimH and FliC. Rotavirus naïve adult BALB/cJ mice were orally immunized followed by murine rotavirus strain ECWT viral challenge. Antirotavirus serum IgG and antigen-specific antibody-secreting cell responses were detected in rLA-vaccinated mice. A day after the oral rotavirus challenge, fecal antigen shedding was significantly decreased in the rLA group. These results demonstrate the potential of rLA platforms to generate protective mucosal immunity. Additionally, metagenomic and metatranscriptomic analyses of exogenous probiotic administration within the murine small intestine revealed differences between LA genome expression and the whole metatranscriptome in recombinant- versus wild-type LA-vaccinated mice. LA genome expression in rLA-vaccinated mice had decreased carbohydrate metabolism and increased stress responses. We also detected antigen and adjuvant transcript expression only in mice exposed to the rLA platform. There was relative enrichment of probiotic species in the wild-type group with overall increased α- and β-diversity in the buffer compared to probiotic groups. These results highlight the interactions between an exogenous probiotic and the host microbiome at an immune inductive site. Finally, we used an in vitro model to evaluate modulation of polyunsaturated fatty acid (PUFA) metabolism on host cell and (r)LA interactions. Both (r)LA and PUFA treatments significantly changed pathogen recognition receptor expression. (r)LA treatment mainly altered inflammatory cytokine expression while PUFA supplementation primarily influenced mucin expression. rLA strains adhered more to host cells than wild-type LA while the rLA strain expressing both antigens and adjuvants may better prevent E. coli adhesion. These results and methodologies provide a starting point for further investigation into PUFA metabolism as a mechanism for improving rLA immunogenicity and competition against other enteric pathogens.
dc.format.mediumborn digital
dc.format.mediumdoctoral dissertations
dc.identifierGilfillan_colostate_0053A_18394.pdf
dc.identifier.urihttps://hdl.handle.net/10217/239206
dc.languageEnglish
dc.language.isoeng
dc.publisherColorado State University. Libraries
dc.relation.ispartof2020-
dc.rightsCopyright and other restrictions may apply. User is responsible for compliance with all applicable laws. For information about copyright law, please see https://libguides.colostate.edu/copyright.
dc.rights.accessEmbargo expires: 08/16/2026.
dc.titleThe adventures of Lactobacillus acidophilus: evaluating a recombinant probiotic rotavirus vaccine from host and microbial perspectives
dc.typeText
dcterms.embargo.expires2026-08-16
dcterms.embargo.terms2026-08-16
dcterms.rights.dplaThis Item is protected by copyright and/or related rights (https://rightsstatements.org/vocab/InC/1.0/). You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s).
thesis.degree.disciplineMicrobiology, Immunology, and Pathology
thesis.degree.grantorColorado State University
thesis.degree.levelDoctoral
thesis.degree.nameDoctor of Philosophy (Ph.D.)

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