<i>Lactobacillus acidophilus</i> Expressing Murine Rotavirus VP8 and Mucosal Adjuvants Induce Virus-Specific Immune Responses
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...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-11-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/11/12/1774 |
| _version_ | 1827573350688358400 |
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| author | Darby Gilfillan Allison C. Vilander Meichen Pan Yong Jun Goh Sarah O’Flaherty Ningguo Feng Bridget E. Fox Callie Lang Harry B. Greenberg Zaid Abdo Rodolphe Barrangou Gregg A. Dean |
| author_facet | Darby Gilfillan Allison C. Vilander Meichen Pan Yong Jun Goh Sarah O’Flaherty Ningguo Feng Bridget E. Fox Callie Lang Harry B. Greenberg Zaid Abdo Rodolphe Barrangou Gregg A. Dean |
| author_sort | Darby Gilfillan |
| collection | DOAJ |
| description | 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 <i>Lactobacillus acidophilus</i> (rLA) vaccine expressing rotavirus antigens of the VP8* domain from the rotavirus EDIM VP4 capsid protein along with the adjuvants FimH and FliC. The <i>upp</i>-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 <i>L. acidophilus</i> 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 EC<sub>WT</sub> 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. |
| first_indexed | 2024-03-08T20:18:07Z |
| format | Article |
| id | doaj.art-6b1ecc51535b4485ab8817aaea4e76f4 |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-03-08T20:18:07Z |
| publishDate | 2023-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-6b1ecc51535b4485ab8817aaea4e76f42023-12-22T14:47:02ZengMDPI AGVaccines2076-393X2023-11-011112177410.3390/vaccines11121774<i>Lactobacillus acidophilus</i> Expressing Murine Rotavirus VP8 and Mucosal Adjuvants Induce Virus-Specific Immune ResponsesDarby Gilfillan0Allison C. Vilander1Meichen Pan2Yong Jun Goh3Sarah O’Flaherty4Ningguo Feng5Bridget E. Fox6Callie Lang7Harry B. Greenberg8Zaid Abdo9Rodolphe Barrangou10Gregg A. Dean11Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USADepartment of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USADepartment of Food, Bioprocessing and Nutrition Sciences, North Carolina State University, Raleigh, NC 27695, USADepartment of Food, Bioprocessing and Nutrition Sciences, North Carolina State University, Raleigh, NC 27695, USADepartment of Food, Bioprocessing and Nutrition Sciences, North Carolina State University, Raleigh, NC 27695, USADepartments of Medicine and Microbiology and Immunology, School of Medicine, Stanford University, Stanford, CA 94305, USADepartment of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USADepartment of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USADepartments of Medicine and Microbiology and Immunology, School of Medicine, Stanford University, Stanford, CA 94305, USADepartment of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USADepartment of Food, Bioprocessing and Nutrition Sciences, North Carolina State University, Raleigh, NC 27695, USADepartment of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USARotavirus 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 <i>Lactobacillus acidophilus</i> (rLA) vaccine expressing rotavirus antigens of the VP8* domain from the rotavirus EDIM VP4 capsid protein along with the adjuvants FimH and FliC. The <i>upp</i>-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 <i>L. acidophilus</i> 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 EC<sub>WT</sub> 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.https://www.mdpi.com/2076-393X/11/12/1774rotavirus<i>Lactobacillus acidophilus</i>next-generation vaccine |
| spellingShingle | Darby Gilfillan Allison C. Vilander Meichen Pan Yong Jun Goh Sarah O’Flaherty Ningguo Feng Bridget E. Fox Callie Lang Harry B. Greenberg Zaid Abdo Rodolphe Barrangou Gregg A. Dean <i>Lactobacillus acidophilus</i> Expressing Murine Rotavirus VP8 and Mucosal Adjuvants Induce Virus-Specific Immune Responses Vaccines rotavirus <i>Lactobacillus acidophilus</i> next-generation vaccine |
| title | <i>Lactobacillus acidophilus</i> Expressing Murine Rotavirus VP8 and Mucosal Adjuvants Induce Virus-Specific Immune Responses |
| title_full | <i>Lactobacillus acidophilus</i> Expressing Murine Rotavirus VP8 and Mucosal Adjuvants Induce Virus-Specific Immune Responses |
| title_fullStr | <i>Lactobacillus acidophilus</i> Expressing Murine Rotavirus VP8 and Mucosal Adjuvants Induce Virus-Specific Immune Responses |
| title_full_unstemmed | <i>Lactobacillus acidophilus</i> Expressing Murine Rotavirus VP8 and Mucosal Adjuvants Induce Virus-Specific Immune Responses |
| title_short | <i>Lactobacillus acidophilus</i> Expressing Murine Rotavirus VP8 and Mucosal Adjuvants Induce Virus-Specific Immune Responses |
| title_sort | i lactobacillus acidophilus i expressing murine rotavirus vp8 and mucosal adjuvants induce virus specific immune responses |
| topic | rotavirus <i>Lactobacillus acidophilus</i> next-generation vaccine |
| url | https://www.mdpi.com/2076-393X/11/12/1774 |
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