Combined live oral priming and intramuscular boosting regimen with Rotarix® and a nanoparticle-based trivalent rotavirus vaccine evaluated in gnotobiotic pig models of G4P[6] and G1P[8] human rotavirus infection
Human rotavirus (HRV) is the causative agent of severe dehydrating diarrhea in children under the age of five, resulting in up to 215,000 deaths each year. These deaths almost exclusively occur in low- and middle-income countries where vaccine efficacy is the lowest due to chronic malnutrition, gut...
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| Format: | info:ar-repo/semantics/artículo |
| Language: | Inglés |
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MDPI
2023
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| Online Access: | http://hdl.handle.net/20.500.12123/15201 https://www.mdpi.com/2076-393X/11/5/927 https://doi.org/10.3390/vaccines11050927 |
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| author | Hensley, Casey Nyblade, Charlotte Zhou, Peng Parreño, Gladys Viviana Ramesh, Ashwin Frazier, Annie Frazier, Maggie Garrison, Sarah Fantasia-Davis, Ariana Cai, Ruiqing Huang, Peng-Wei Xia, Ming Tan, Ming Yuan, Lijuan |
| author_browse | Cai, Ruiqing Fantasia-Davis, Ariana Frazier, Annie Frazier, Maggie Garrison, Sarah Hensley, Casey Huang, Peng-Wei Nyblade, Charlotte Parreño, Gladys Viviana Ramesh, Ashwin Tan, Ming Xia, Ming Yuan, Lijuan Zhou, Peng |
| author_facet | Hensley, Casey Nyblade, Charlotte Zhou, Peng Parreño, Gladys Viviana Ramesh, Ashwin Frazier, Annie Frazier, Maggie Garrison, Sarah Fantasia-Davis, Ariana Cai, Ruiqing Huang, Peng-Wei Xia, Ming Tan, Ming Yuan, Lijuan |
| author_sort | Hensley, Casey |
| collection | INTA Digital |
| description | Human rotavirus (HRV) is the causative agent of severe dehydrating diarrhea in children under the age of five, resulting in up to 215,000 deaths each year. These deaths almost exclusively occur in low- and middle-income countries where vaccine efficacy is the lowest due to chronic malnutrition, gut dysbiosis, and concurrent enteric viral infection. Parenteral vaccines for HRV are particularly attractive as they avoid many of the concerns associated with currently used live oral vaccines. In this study, a two-dose intramuscular (IM) regimen of the trivalent, nanoparticle-based, nonreplicating HRV vaccine (trivalent S60-VP8*), utilizing the shell (S) domain of the capsid of norovirus as an HRV VP8* antigen display platform, was evaluated for immunogenicity and protective efficacy against P[6] and P[8] HRV using gnotobiotic pig models. A prime–boost strategy using one dose of the oral Rotarix® vaccine, followed by one dose of the IM trivalent nanoparticle vaccine was also evaluated. Both regimens were highly immunogenic in inducing serum virus neutralizing, IgG, and IgA antibodies. The two vaccine regimens failed to confer significant protection against diarrhea; however, the prime–boost regimen significantly shortened the duration of virus shedding in pigs challenged orally with the virulent Wa (G1P[8]) HRV and significantly shortened the mean duration of virus shedding, mean peak titer, and area under the curve of virus shedding after challenge with Arg (G4P[6]) HRV. Prime–boost-vaccinated pigs challenged with P[8] HRV had significantly higher P[8]-specific IgG antibody-secreting cells (ASCs) in the spleen post-challenge. Prime–boost-vaccinated pigs challenged with P[6] HRV had significantly higher numbers of P[6]- and P[8]-specific IgG ASCs in the ileum, as well as significantly higher numbers of P[8]-specific IgA ASCs in the spleen post-challenge. These results suggest the promise of and warrant further investigation into the oral priming and parenteral boosting strategy for future HRV vaccines. |
| format | info:ar-repo/semantics/artículo |
| id | INTA15201 |
| institution | Instituto Nacional de Tecnología Agropecuaria (INTA -Argentina) |
| language | Inglés |
| publishDate | 2023 |
| publishDateRange | 2023 |
| publishDateSort | 2023 |
| publisher | MDPI |
| publisherStr | MDPI |
| record_format | dspace |
| spelling | INTA152012023-09-13T14:02:11Z Combined live oral priming and intramuscular boosting regimen with Rotarix® and a nanoparticle-based trivalent rotavirus vaccine evaluated in gnotobiotic pig models of G4P[6] and G1P[8] human rotavirus infection Hensley, Casey Nyblade, Charlotte Zhou, Peng Parreño, Gladys Viviana Ramesh, Ashwin Frazier, Annie Frazier, Maggie Garrison, Sarah Fantasia-Davis, Ariana Cai, Ruiqing Huang, Peng-Wei Xia, Ming Tan, Ming Yuan, Lijuan Rotavirus Nanoparticles Gnotobiotic Animals Swine Vaccines Nanopartículas Animales Notobióticos Cerdo Vacuna Human Rotavirus Infection Infección por Rotavirus Humano Human rotavirus (HRV) is the causative agent of severe dehydrating diarrhea in children under the age of five, resulting in up to 215,000 deaths each year. These deaths almost exclusively occur in low- and middle-income countries where vaccine efficacy is the lowest due to chronic malnutrition, gut dysbiosis, and concurrent enteric viral infection. Parenteral vaccines for HRV are particularly attractive as they avoid many of the concerns associated with currently used live oral vaccines. In this study, a two-dose intramuscular (IM) regimen of the trivalent, nanoparticle-based, nonreplicating HRV vaccine (trivalent S60-VP8*), utilizing the shell (S) domain of the capsid of norovirus as an HRV VP8* antigen display platform, was evaluated for immunogenicity and protective efficacy against P[6] and P[8] HRV using gnotobiotic pig models. A prime–boost strategy using one dose of the oral Rotarix® vaccine, followed by one dose of the IM trivalent nanoparticle vaccine was also evaluated. Both regimens were highly immunogenic in inducing serum virus neutralizing, IgG, and IgA antibodies. The two vaccine regimens failed to confer significant protection against diarrhea; however, the prime–boost regimen significantly shortened the duration of virus shedding in pigs challenged orally with the virulent Wa (G1P[8]) HRV and significantly shortened the mean duration of virus shedding, mean peak titer, and area under the curve of virus shedding after challenge with Arg (G4P[6]) HRV. Prime–boost-vaccinated pigs challenged with P[8] HRV had significantly higher P[8]-specific IgG antibody-secreting cells (ASCs) in the spleen post-challenge. Prime–boost-vaccinated pigs challenged with P[6] HRV had significantly higher numbers of P[6]- and P[8]-specific IgG ASCs in the ileum, as well as significantly higher numbers of P[8]-specific IgA ASCs in the spleen post-challenge. These results suggest the promise of and warrant further investigation into the oral priming and parenteral boosting strategy for future HRV vaccines. Instituto de Virología Fil: Hensley, Casey. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados Unidos Fil: Nyblade, Charlotte. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados Unidos Fil: Zhou, Peng. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados Unidos Fil: Parreño, Gladys Viviana. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados Unidos Fil: Parreño, Gladys Viviana. Instituto Nacional de Tecnología Agropecuaria (INTA). INCUINTA. Instituto de Virologia e Innovaciones Tecnologicas (IVIT); Argentina Fil: Parreño, Gladys Viviana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Ramesh, Ashwin. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados Unidos Fil: Frazier, Annie. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados Unidos Fil: Frazier, Maggie. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados Unidos Fil: Garrison, Sarah. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados Unidos Fil: Fantasia-Davis, Ariana. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados Unidos Fil: Cai, Ruiqing. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados Unidos Fil: Huang, Peng-Wei. Cincinnati Children’s Hospital Medical Center. Division of Infectious Diseases; Estados Unidos Fil: Xia, Ming. Cincinnati Children’s Hospital Medical Center. Division of Infectious Diseases; Estados Unidos Fil: Tan, Ming. Cincinnati Children’s Hospital Medical Center. Division of Infectious Diseases; Estados Unidos Fil: Tan, Ming. University of Cincinnati College of Medicine. Department of Pediatrics; Estados Unidos Fil: Yuan, Lijuan. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados Unidos 2023-09-13T13:57:21Z 2023-09-13T13:57:21Z 2023-05 info:ar-repo/semantics/artículo info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://hdl.handle.net/20.500.12123/15201 https://www.mdpi.com/2076-393X/11/5/927 2076-393X https://doi.org/10.3390/vaccines11050927 eng info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by-nc-sa/4.0/ Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) application/pdf MDPI Vaccines 11 (5) : 927 (Mayo 2023) |
| spellingShingle | Rotavirus Nanoparticles Gnotobiotic Animals Swine Vaccines Nanopartículas Animales Notobióticos Cerdo Vacuna Human Rotavirus Infection Infección por Rotavirus Humano Hensley, Casey Nyblade, Charlotte Zhou, Peng Parreño, Gladys Viviana Ramesh, Ashwin Frazier, Annie Frazier, Maggie Garrison, Sarah Fantasia-Davis, Ariana Cai, Ruiqing Huang, Peng-Wei Xia, Ming Tan, Ming Yuan, Lijuan Combined live oral priming and intramuscular boosting regimen with Rotarix® and a nanoparticle-based trivalent rotavirus vaccine evaluated in gnotobiotic pig models of G4P[6] and G1P[8] human rotavirus infection |
| title | Combined live oral priming and intramuscular boosting regimen with Rotarix® and a nanoparticle-based trivalent rotavirus vaccine evaluated in gnotobiotic pig models of G4P[6] and G1P[8] human rotavirus infection |
| title_full | Combined live oral priming and intramuscular boosting regimen with Rotarix® and a nanoparticle-based trivalent rotavirus vaccine evaluated in gnotobiotic pig models of G4P[6] and G1P[8] human rotavirus infection |
| title_fullStr | Combined live oral priming and intramuscular boosting regimen with Rotarix® and a nanoparticle-based trivalent rotavirus vaccine evaluated in gnotobiotic pig models of G4P[6] and G1P[8] human rotavirus infection |
| title_full_unstemmed | Combined live oral priming and intramuscular boosting regimen with Rotarix® and a nanoparticle-based trivalent rotavirus vaccine evaluated in gnotobiotic pig models of G4P[6] and G1P[8] human rotavirus infection |
| title_short | Combined live oral priming and intramuscular boosting regimen with Rotarix® and a nanoparticle-based trivalent rotavirus vaccine evaluated in gnotobiotic pig models of G4P[6] and G1P[8] human rotavirus infection |
| title_sort | combined live oral priming and intramuscular boosting regimen with rotarix r and a nanoparticle based trivalent rotavirus vaccine evaluated in gnotobiotic pig models of g4p 6 and g1p 8 human rotavirus infection |
| topic | Rotavirus Nanoparticles Gnotobiotic Animals Swine Vaccines Nanopartículas Animales Notobióticos Cerdo Vacuna Human Rotavirus Infection Infección por Rotavirus Humano |
| url | http://hdl.handle.net/20.500.12123/15201 https://www.mdpi.com/2076-393X/11/5/927 https://doi.org/10.3390/vaccines11050927 |
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