Thermostable, Dissolvable Buccal Film Rotavirus Vaccine Is Highly Effective in Neonatal Gnotobiotic Pig Challenge Model
Difficulties related to storage and transport of currently available live oral rotavirus vaccines can have detrimental consequences on the efficacy of the vaccines. Thus, there is a great need for thermostable vaccines that can eliminate the necessity for cold chain storage or reconstitution before...
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MDPI AG
2021-04-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/9/5/437 |
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| author | Casey Hensley Peng Zhou Sofia Schnur Hassan M. Mahsoub Yu Liang Min-Xuan Wang Caroline Page Lijuan Yuan Victor Bronshtein |
| author_facet | Casey Hensley Peng Zhou Sofia Schnur Hassan M. Mahsoub Yu Liang Min-Xuan Wang Caroline Page Lijuan Yuan Victor Bronshtein |
| author_sort | Casey Hensley |
| collection | DOAJ |
| description | Difficulties related to storage and transport of currently available live oral rotavirus vaccines can have detrimental consequences on the efficacy of the vaccines. Thus, there is a great need for thermostable vaccines that can eliminate the necessity for cold chain storage or reconstitution before administration. In this study, we developed a dissolvable oral polymeric film comprised of a live attenuated thermostable tetravalent rhesus-human reassortant rotavirus vaccine (RRV-TV) powder and antacid (CaCO<sub>3</sub>). Immunogenicity and protective efficacy of the vaccine after buccal delivery was evaluated in the gnotobiotic pig model of human rotavirus (HRV) infection and diarrhea. Two doses of the vaccine were highly immunogenic and conferred strong protection against virus shedding and diarrhea upon challenge with a high dose of a virulent G1 HRV in gnotobiotic pigs. Those pigs vaccinated with the preserved film vaccine had significantly delayed onset of diarrhea; reduced duration and area under the curve of diarrhea; delayed onset of fecal virus shedding; and reduced duration and peak of fecal virus shedding titers compared to pigs in both the placebo and the reconstituted liquid oral RRV-TV vaccine groups. Associated with the strong protection, high titers of serum virus neutralization antibodies against each of the four RRV-TV mono-reassortants and G1 HRV-specific serum IgA and IgG antibodies, as well as intestinal IgA antibodies, were induced by the preserved film vaccine. These results demonstrated the effectiveness of our thermostable buccal film rotavirus vaccine and warrant further investigation into the promise of the novel technology in addressing drawbacks of the current live oral HRV vaccines. |
| first_indexed | 2024-03-10T11:46:27Z |
| format | Article |
| id | doaj.art-a311cd83406b412a9dc9b6e389dff695 |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-03-10T11:46:27Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-a311cd83406b412a9dc9b6e389dff6952023-11-21T18:01:55ZengMDPI AGVaccines2076-393X2021-04-019543710.3390/vaccines9050437Thermostable, Dissolvable Buccal Film Rotavirus Vaccine Is Highly Effective in Neonatal Gnotobiotic Pig Challenge ModelCasey Hensley0Peng Zhou1Sofia Schnur2Hassan M. Mahsoub3Yu Liang4Min-Xuan Wang5Caroline Page6Lijuan Yuan7Victor Bronshtein8Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA 24061, USADepartment of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA 24061, USADepartment of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA 24061, USADepartment of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA 24061, USADepartment of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA 24061, USAUniversal Stabilization Technologies, Inc., San Diego, CA 92121, USAUniversal Stabilization Technologies, Inc., San Diego, CA 92121, USADepartment of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA 24061, USAUniversal Stabilization Technologies, Inc., San Diego, CA 92121, USADifficulties related to storage and transport of currently available live oral rotavirus vaccines can have detrimental consequences on the efficacy of the vaccines. Thus, there is a great need for thermostable vaccines that can eliminate the necessity for cold chain storage or reconstitution before administration. In this study, we developed a dissolvable oral polymeric film comprised of a live attenuated thermostable tetravalent rhesus-human reassortant rotavirus vaccine (RRV-TV) powder and antacid (CaCO<sub>3</sub>). Immunogenicity and protective efficacy of the vaccine after buccal delivery was evaluated in the gnotobiotic pig model of human rotavirus (HRV) infection and diarrhea. Two doses of the vaccine were highly immunogenic and conferred strong protection against virus shedding and diarrhea upon challenge with a high dose of a virulent G1 HRV in gnotobiotic pigs. Those pigs vaccinated with the preserved film vaccine had significantly delayed onset of diarrhea; reduced duration and area under the curve of diarrhea; delayed onset of fecal virus shedding; and reduced duration and peak of fecal virus shedding titers compared to pigs in both the placebo and the reconstituted liquid oral RRV-TV vaccine groups. Associated with the strong protection, high titers of serum virus neutralization antibodies against each of the four RRV-TV mono-reassortants and G1 HRV-specific serum IgA and IgG antibodies, as well as intestinal IgA antibodies, were induced by the preserved film vaccine. These results demonstrated the effectiveness of our thermostable buccal film rotavirus vaccine and warrant further investigation into the promise of the novel technology in addressing drawbacks of the current live oral HRV vaccines.https://www.mdpi.com/2076-393X/9/5/437thermostableoral film vaccinerotavirusdiarrheagnotobiotic pigs |
| spellingShingle | Casey Hensley Peng Zhou Sofia Schnur Hassan M. Mahsoub Yu Liang Min-Xuan Wang Caroline Page Lijuan Yuan Victor Bronshtein Thermostable, Dissolvable Buccal Film Rotavirus Vaccine Is Highly Effective in Neonatal Gnotobiotic Pig Challenge Model Vaccines thermostable oral film vaccine rotavirus diarrhea gnotobiotic pigs |
| title | Thermostable, Dissolvable Buccal Film Rotavirus Vaccine Is Highly Effective in Neonatal Gnotobiotic Pig Challenge Model |
| title_full | Thermostable, Dissolvable Buccal Film Rotavirus Vaccine Is Highly Effective in Neonatal Gnotobiotic Pig Challenge Model |
| title_fullStr | Thermostable, Dissolvable Buccal Film Rotavirus Vaccine Is Highly Effective in Neonatal Gnotobiotic Pig Challenge Model |
| title_full_unstemmed | Thermostable, Dissolvable Buccal Film Rotavirus Vaccine Is Highly Effective in Neonatal Gnotobiotic Pig Challenge Model |
| title_short | Thermostable, Dissolvable Buccal Film Rotavirus Vaccine Is Highly Effective in Neonatal Gnotobiotic Pig Challenge Model |
| title_sort | thermostable dissolvable buccal film rotavirus vaccine is highly effective in neonatal gnotobiotic pig challenge model |
| topic | thermostable oral film vaccine rotavirus diarrhea gnotobiotic pigs |
| url | https://www.mdpi.com/2076-393X/9/5/437 |
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