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Published on: January 28, 2019
Lactobacillus acidophilus Expressing Murine Rotavirus VP8 and Mucosal Adjuvants Induce Virus-Specific Immune
Darby Gilfillan1, Allison C Vilander1, Meichen Pan2
1Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA.
Insights
A novel probiotic vaccine using Lactobacillus acidophilus expressing rotavirus antigens showed modest protection against rotavirus challenge in mice. This next-generation vaccine approach could improve efficacy in diverse global settings.
Area of Science:
- Microbiology
- Vaccinology
- Immunology
Background:
- Rotavirus diarrhea is a leading cause of death in children under five globally.
- Existing rotavirus vaccines exhibit variable performance in high- vs. low-middle-income countries.
- Next-generation probiotic vaccines offer a potential solution to bridge this efficacy gap.
Purpose of the Study:
- To develop and evaluate a novel recombinant Lactobacillus acidophilus (rLA) probiotic vaccine expressing rotavirus antigens.
- To assess the immunogenicity and protective efficacy of the rLA vaccine against rotavirus challenge in a murine model.
Main Methods:
- Constructed a novel rLA vaccine expressing rotavirus VP8* antigens and adjuvants (FimH, FliC) using a gene-replacement system and plasmid.
- Confirmed antigen and adjuvant expression via flow cytometry and Western blot.
- Orally immunized rotavirus-naïve mice, followed by challenge with murine rotavirus strain ECWT.
Main Results:
- rLA-vaccinated mice demonstrated detectable anti-rotavirus serum IgG and antibody-secreting cell responses.
- Significantly reduced fecal antigen shedding was observed in the rLA group one day post-challenge.
- The study successfully constructed novel rLA constructs expressing VP8 antigens.
Conclusions:
- Novel rLA constructs expressing VP8 can be successfully generated.
- These constructs induced modest homotypic protection against rotavirus challenge in an adult murine model.
- This indicates potential for a probiotic next-generation vaccine against human rotavirus.
Abstract:
Rotavirus diarrhea-associated illness remains a major cause of global death in children under five, attributable in part to discrepancies in vaccine performance between high- and low-middle-income countries. Next-generation probiotic vaccines could help bridge this efficacy gap. We developed a novel recombinant Lactobacillus acidophilus (rLA) vaccine expressing rotavirus antigens of the VP8* domain from the rotavirus EDIM VP4 capsid protein along with the adjuvants FimH and FliC. The upp-based counterselective gene-replacement system was used to chromosomally integrate FimH, VP8Pep (10 amino acid epitope), and VP8-1 (206 amino acid protein) into the L. acidophilus genome, with FliC expressed from a plasmid. VP8 antigen and adjuvant expression were confirmed by flow cytometry and Western blot. 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 indicate that novel rLA constructs expressing VP8 can be successfully constructed and used to generate modest homotypic protection from rotavirus challenge in an adult murine model, indicating the potential for a probiotic next-generation vaccine construct against human rotavirus.
