mRNA-Based Vaccines Are Highly Immunogenic and Confer Protection in the Gnotobiotic Pig Model of Human Rotavirus Diarrhea

Human rotavirus (HRV) is still a leading cause of severe dehydrating gastroenteritis globally, particularly in infants and children. Previously, we demonstrated the immunogenicity of mRNA-based HRV vaccine candidates expressing the viral spike protein VP8* in rodent models. In the present study, we assessed the immunogenicity and protective efficacy of two mRNA-based HRV trivalent vaccine candidates, encoding VP8* of the genotypes P[8], P[6], or P[4], in the gnotobiotic (Gn) pig model of Wa (G1P[8]) HRV infection and diarrhea. Vaccines either encoded VP8* alone fused to the universal T-cell epitope P2 (P2-VP8*) or expressed P2-VP8* as a fusion protein with lumazine synthase (LS-P2-VP8*) to allow the formation and secretion of protein particles that present VP8* on their surface. Gn pigs were randomly assigned into groups and immunized three times with either P2-VP8* (30 µg) or LS-P2-VP8* (30 µg or 12 µg). A trivalent alum-adjuvanted P2-VP8* protein vaccine or an LNP-formulated irrelevant mRNA vaccine served as the positive and negative control, respectively. Upon challenge with virulent Wa HRV, a significantly shortened duration and decreased severity of diarrhea and significant protection from virus shedding was induced by both mRNA vaccine candidates compared to the negative control. Both LS-P2-VP8* doses induced significantly higher VP8*-specific IgG antibody titers in the serum after immunizations than the negative as well as the protein control. The P[8] VP8*-specific IgG antibody-secreting cells in the ileum, spleen, and blood seven days post-challenge, as well as VP8*-specific IFN-γ-producing T-cell numbers increased in all three mRNA-vaccinated pig groups compared to the negative control. Overall, there was a clear tendency towards improved responses in LS-P2-VP8* compared to the P2-VP8*mRNA vaccine. The demonstrated strong humoral immune responses, priming for effector T cells, and the significant reduction of viral shedding and duration of diarrhea in Gn pigs provide a promising proof of concept and may provide guidance for the further development of mRNA-based rotavirus vaccines. Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Casey Hensley [verfasserIn] Sandro Roier [verfasserIn] Peng Zhou [verfasserIn] Sofia Schnur [verfasserIn] Charlotte Nyblade [verfasserIn] Viviana Parreno [verfasserIn] Annie Frazier [verfasserIn] Maggie Frazier [verfasserIn] Kelsey Kiley [verfasserIn] Samantha O’Brien [verfasserIn] Yu Liang [verfasserIn] Bryan T. Mayer [verfasserIn] Ruizhe Wu [verfasserIn] Celia Mahoney [verfasserIn] Monica M. McNeal [verfasserIn] Benjamin Petsch [verfasserIn] Susanne Rauch [verfasserIn] Lijuan Yuan [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2024

Schlagwörter:	rotavirus mRNA vaccine gnotobiotic pigs P2-VP8* diarrhea

Übergeordnetes Werk:	In: Vaccines - MDPI AG, 2013, 12(2024), 3, p 260
Übergeordnetes Werk:	volume:12 ; year:2024 ; number:3, p 260

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3390/vaccines12030260

Katalog-ID:	DOAJ099806223

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allfields	10.3390/vaccines12030260 doi (DE-627)DOAJ099806223 (DE-599)DOAJcb5a7873ad0641e491f027758ab5b5e0 DE-627 ger DE-627 rakwb eng Casey Hensley verfasserin aut mRNA-Based Vaccines Are Highly Immunogenic and Confer Protection in the Gnotobiotic Pig Model of Human Rotavirus Diarrhea 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Human rotavirus (HRV) is still a leading cause of severe dehydrating gastroenteritis globally, particularly in infants and children. Previously, we demonstrated the immunogenicity of mRNA-based HRV vaccine candidates expressing the viral spike protein VP8* in rodent models. In the present study, we assessed the immunogenicity and protective efficacy of two mRNA-based HRV trivalent vaccine candidates, encoding VP8* of the genotypes P[8], P[6], or P[4], in the gnotobiotic (Gn) pig model of Wa (G1P[8]) HRV infection and diarrhea. Vaccines either encoded VP8* alone fused to the universal T-cell epitope P2 (P2-VP8) or expressed P2-VP8 as a fusion protein with lumazine synthase (LS-P2-VP8) to allow the formation and secretion of protein particles that present VP8 on their surface. Gn pigs were randomly assigned into groups and immunized three times with either P2-VP8* (30 µg) or LS-P2-VP8* (30 µg or 12 µg). A trivalent alum-adjuvanted P2-VP8* protein vaccine or an LNP-formulated irrelevant mRNA vaccine served as the positive and negative control, respectively. Upon challenge with virulent Wa HRV, a significantly shortened duration and decreased severity of diarrhea and significant protection from virus shedding was induced by both mRNA vaccine candidates compared to the negative control. Both LS-P2-VP8* doses induced significantly higher VP8-specific IgG antibody titers in the serum after immunizations than the negative as well as the protein control. The P[8] VP8-specific IgG antibody-secreting cells in the ileum, spleen, and blood seven days post-challenge, as well as VP8-specific IFN-γ-producing T-cell numbers increased in all three mRNA-vaccinated pig groups compared to the negative control. Overall, there was a clear tendency towards improved responses in LS-P2-VP8 compared to the P2-VP8mRNA vaccine. The demonstrated strong humoral immune responses, priming for effector T cells, and the significant reduction of viral shedding and duration of diarrhea in Gn pigs provide a promising proof of concept and may provide guidance for the further development of mRNA-based rotavirus vaccines. rotavirus mRNA vaccine gnotobiotic pigs P2-VP8 diarrhea Medicine R Sandro Roier verfasserin aut Peng Zhou verfasserin aut Sofia Schnur verfasserin aut Charlotte Nyblade verfasserin aut Viviana Parreno verfasserin aut Annie Frazier verfasserin aut Maggie Frazier verfasserin aut Kelsey Kiley verfasserin aut Samantha O’Brien verfasserin aut Yu Liang verfasserin aut Bryan T. Mayer verfasserin aut Ruizhe Wu verfasserin aut Celia Mahoney verfasserin aut Monica M. McNeal verfasserin aut Benjamin Petsch verfasserin aut Susanne Rauch verfasserin aut Lijuan Yuan verfasserin aut In Vaccines MDPI AG, 2013 12(2024), 3, p 260 (DE-627)736559205 (DE-600)2703319-3 2076393X nnns volume:12 year:2024 number:3, p 260 https://doi.org/10.3390/vaccines12030260 kostenfrei https://doaj.org/article/cb5a7873ad0641e491f027758ab5b5e0 kostenfrei https://www.mdpi.com/2076-393X/12/3/260 kostenfrei https://doaj.org/toc/2076-393X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2024 3, p 260
spelling	10.3390/vaccines12030260 doi (DE-627)DOAJ099806223 (DE-599)DOAJcb5a7873ad0641e491f027758ab5b5e0 DE-627 ger DE-627 rakwb eng Casey Hensley verfasserin aut mRNA-Based Vaccines Are Highly Immunogenic and Confer Protection in the Gnotobiotic Pig Model of Human Rotavirus Diarrhea 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Human rotavirus (HRV) is still a leading cause of severe dehydrating gastroenteritis globally, particularly in infants and children. Previously, we demonstrated the immunogenicity of mRNA-based HRV vaccine candidates expressing the viral spike protein VP8* in rodent models. In the present study, we assessed the immunogenicity and protective efficacy of two mRNA-based HRV trivalent vaccine candidates, encoding VP8* of the genotypes P[8], P[6], or P[4], in the gnotobiotic (Gn) pig model of Wa (G1P[8]) HRV infection and diarrhea. Vaccines either encoded VP8* alone fused to the universal T-cell epitope P2 (P2-VP8) or expressed P2-VP8 as a fusion protein with lumazine synthase (LS-P2-VP8) to allow the formation and secretion of protein particles that present VP8 on their surface. Gn pigs were randomly assigned into groups and immunized three times with either P2-VP8* (30 µg) or LS-P2-VP8* (30 µg or 12 µg). A trivalent alum-adjuvanted P2-VP8* protein vaccine or an LNP-formulated irrelevant mRNA vaccine served as the positive and negative control, respectively. Upon challenge with virulent Wa HRV, a significantly shortened duration and decreased severity of diarrhea and significant protection from virus shedding was induced by both mRNA vaccine candidates compared to the negative control. Both LS-P2-VP8* doses induced significantly higher VP8-specific IgG antibody titers in the serum after immunizations than the negative as well as the protein control. The P[8] VP8-specific IgG antibody-secreting cells in the ileum, spleen, and blood seven days post-challenge, as well as VP8-specific IFN-γ-producing T-cell numbers increased in all three mRNA-vaccinated pig groups compared to the negative control. Overall, there was a clear tendency towards improved responses in LS-P2-VP8 compared to the P2-VP8mRNA vaccine. The demonstrated strong humoral immune responses, priming for effector T cells, and the significant reduction of viral shedding and duration of diarrhea in Gn pigs provide a promising proof of concept and may provide guidance for the further development of mRNA-based rotavirus vaccines. rotavirus mRNA vaccine gnotobiotic pigs P2-VP8 diarrhea Medicine R Sandro Roier verfasserin aut Peng Zhou verfasserin aut Sofia Schnur verfasserin aut Charlotte Nyblade verfasserin aut Viviana Parreno verfasserin aut Annie Frazier verfasserin aut Maggie Frazier verfasserin aut Kelsey Kiley verfasserin aut Samantha O’Brien verfasserin aut Yu Liang verfasserin aut Bryan T. Mayer verfasserin aut Ruizhe Wu verfasserin aut Celia Mahoney verfasserin aut Monica M. McNeal verfasserin aut Benjamin Petsch verfasserin aut Susanne Rauch verfasserin aut Lijuan Yuan verfasserin aut In Vaccines MDPI AG, 2013 12(2024), 3, p 260 (DE-627)736559205 (DE-600)2703319-3 2076393X nnns volume:12 year:2024 number:3, p 260 https://doi.org/10.3390/vaccines12030260 kostenfrei https://doaj.org/article/cb5a7873ad0641e491f027758ab5b5e0 kostenfrei https://www.mdpi.com/2076-393X/12/3/260 kostenfrei https://doaj.org/toc/2076-393X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2024 3, p 260
allfields_unstemmed	10.3390/vaccines12030260 doi (DE-627)DOAJ099806223 (DE-599)DOAJcb5a7873ad0641e491f027758ab5b5e0 DE-627 ger DE-627 rakwb eng Casey Hensley verfasserin aut mRNA-Based Vaccines Are Highly Immunogenic and Confer Protection in the Gnotobiotic Pig Model of Human Rotavirus Diarrhea 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Human rotavirus (HRV) is still a leading cause of severe dehydrating gastroenteritis globally, particularly in infants and children. Previously, we demonstrated the immunogenicity of mRNA-based HRV vaccine candidates expressing the viral spike protein VP8* in rodent models. In the present study, we assessed the immunogenicity and protective efficacy of two mRNA-based HRV trivalent vaccine candidates, encoding VP8* of the genotypes P[8], P[6], or P[4], in the gnotobiotic (Gn) pig model of Wa (G1P[8]) HRV infection and diarrhea. Vaccines either encoded VP8* alone fused to the universal T-cell epitope P2 (P2-VP8) or expressed P2-VP8 as a fusion protein with lumazine synthase (LS-P2-VP8) to allow the formation and secretion of protein particles that present VP8 on their surface. Gn pigs were randomly assigned into groups and immunized three times with either P2-VP8* (30 µg) or LS-P2-VP8* (30 µg or 12 µg). A trivalent alum-adjuvanted P2-VP8* protein vaccine or an LNP-formulated irrelevant mRNA vaccine served as the positive and negative control, respectively. Upon challenge with virulent Wa HRV, a significantly shortened duration and decreased severity of diarrhea and significant protection from virus shedding was induced by both mRNA vaccine candidates compared to the negative control. Both LS-P2-VP8* doses induced significantly higher VP8-specific IgG antibody titers in the serum after immunizations than the negative as well as the protein control. The P[8] VP8-specific IgG antibody-secreting cells in the ileum, spleen, and blood seven days post-challenge, as well as VP8-specific IFN-γ-producing T-cell numbers increased in all three mRNA-vaccinated pig groups compared to the negative control. Overall, there was a clear tendency towards improved responses in LS-P2-VP8 compared to the P2-VP8mRNA vaccine. The demonstrated strong humoral immune responses, priming for effector T cells, and the significant reduction of viral shedding and duration of diarrhea in Gn pigs provide a promising proof of concept and may provide guidance for the further development of mRNA-based rotavirus vaccines. rotavirus mRNA vaccine gnotobiotic pigs P2-VP8 diarrhea Medicine R Sandro Roier verfasserin aut Peng Zhou verfasserin aut Sofia Schnur verfasserin aut Charlotte Nyblade verfasserin aut Viviana Parreno verfasserin aut Annie Frazier verfasserin aut Maggie Frazier verfasserin aut Kelsey Kiley verfasserin aut Samantha O’Brien verfasserin aut Yu Liang verfasserin aut Bryan T. Mayer verfasserin aut Ruizhe Wu verfasserin aut Celia Mahoney verfasserin aut Monica M. McNeal verfasserin aut Benjamin Petsch verfasserin aut Susanne Rauch verfasserin aut Lijuan Yuan verfasserin aut In Vaccines MDPI AG, 2013 12(2024), 3, p 260 (DE-627)736559205 (DE-600)2703319-3 2076393X nnns volume:12 year:2024 number:3, p 260 https://doi.org/10.3390/vaccines12030260 kostenfrei https://doaj.org/article/cb5a7873ad0641e491f027758ab5b5e0 kostenfrei https://www.mdpi.com/2076-393X/12/3/260 kostenfrei https://doaj.org/toc/2076-393X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2024 3, p 260
allfieldsGer	10.3390/vaccines12030260 doi (DE-627)DOAJ099806223 (DE-599)DOAJcb5a7873ad0641e491f027758ab5b5e0 DE-627 ger DE-627 rakwb eng Casey Hensley verfasserin aut mRNA-Based Vaccines Are Highly Immunogenic and Confer Protection in the Gnotobiotic Pig Model of Human Rotavirus Diarrhea 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Human rotavirus (HRV) is still a leading cause of severe dehydrating gastroenteritis globally, particularly in infants and children. Previously, we demonstrated the immunogenicity of mRNA-based HRV vaccine candidates expressing the viral spike protein VP8* in rodent models. In the present study, we assessed the immunogenicity and protective efficacy of two mRNA-based HRV trivalent vaccine candidates, encoding VP8* of the genotypes P[8], P[6], or P[4], in the gnotobiotic (Gn) pig model of Wa (G1P[8]) HRV infection and diarrhea. Vaccines either encoded VP8* alone fused to the universal T-cell epitope P2 (P2-VP8) or expressed P2-VP8 as a fusion protein with lumazine synthase (LS-P2-VP8) to allow the formation and secretion of protein particles that present VP8 on their surface. Gn pigs were randomly assigned into groups and immunized three times with either P2-VP8* (30 µg) or LS-P2-VP8* (30 µg or 12 µg). A trivalent alum-adjuvanted P2-VP8* protein vaccine or an LNP-formulated irrelevant mRNA vaccine served as the positive and negative control, respectively. Upon challenge with virulent Wa HRV, a significantly shortened duration and decreased severity of diarrhea and significant protection from virus shedding was induced by both mRNA vaccine candidates compared to the negative control. Both LS-P2-VP8* doses induced significantly higher VP8-specific IgG antibody titers in the serum after immunizations than the negative as well as the protein control. The P[8] VP8-specific IgG antibody-secreting cells in the ileum, spleen, and blood seven days post-challenge, as well as VP8-specific IFN-γ-producing T-cell numbers increased in all three mRNA-vaccinated pig groups compared to the negative control. Overall, there was a clear tendency towards improved responses in LS-P2-VP8 compared to the P2-VP8mRNA vaccine. The demonstrated strong humoral immune responses, priming for effector T cells, and the significant reduction of viral shedding and duration of diarrhea in Gn pigs provide a promising proof of concept and may provide guidance for the further development of mRNA-based rotavirus vaccines. rotavirus mRNA vaccine gnotobiotic pigs P2-VP8 diarrhea Medicine R Sandro Roier verfasserin aut Peng Zhou verfasserin aut Sofia Schnur verfasserin aut Charlotte Nyblade verfasserin aut Viviana Parreno verfasserin aut Annie Frazier verfasserin aut Maggie Frazier verfasserin aut Kelsey Kiley verfasserin aut Samantha O’Brien verfasserin aut Yu Liang verfasserin aut Bryan T. Mayer verfasserin aut Ruizhe Wu verfasserin aut Celia Mahoney verfasserin aut Monica M. McNeal verfasserin aut Benjamin Petsch verfasserin aut Susanne Rauch verfasserin aut Lijuan Yuan verfasserin aut In Vaccines MDPI AG, 2013 12(2024), 3, p 260 (DE-627)736559205 (DE-600)2703319-3 2076393X nnns volume:12 year:2024 number:3, p 260 https://doi.org/10.3390/vaccines12030260 kostenfrei https://doaj.org/article/cb5a7873ad0641e491f027758ab5b5e0 kostenfrei https://www.mdpi.com/2076-393X/12/3/260 kostenfrei https://doaj.org/toc/2076-393X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2024 3, p 260
allfieldsSound	10.3390/vaccines12030260 doi (DE-627)DOAJ099806223 (DE-599)DOAJcb5a7873ad0641e491f027758ab5b5e0 DE-627 ger DE-627 rakwb eng Casey Hensley verfasserin aut mRNA-Based Vaccines Are Highly Immunogenic and Confer Protection in the Gnotobiotic Pig Model of Human Rotavirus Diarrhea 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Human rotavirus (HRV) is still a leading cause of severe dehydrating gastroenteritis globally, particularly in infants and children. Previously, we demonstrated the immunogenicity of mRNA-based HRV vaccine candidates expressing the viral spike protein VP8* in rodent models. In the present study, we assessed the immunogenicity and protective efficacy of two mRNA-based HRV trivalent vaccine candidates, encoding VP8* of the genotypes P[8], P[6], or P[4], in the gnotobiotic (Gn) pig model of Wa (G1P[8]) HRV infection and diarrhea. Vaccines either encoded VP8* alone fused to the universal T-cell epitope P2 (P2-VP8) or expressed P2-VP8 as a fusion protein with lumazine synthase (LS-P2-VP8) to allow the formation and secretion of protein particles that present VP8 on their surface. Gn pigs were randomly assigned into groups and immunized three times with either P2-VP8* (30 µg) or LS-P2-VP8* (30 µg or 12 µg). A trivalent alum-adjuvanted P2-VP8* protein vaccine or an LNP-formulated irrelevant mRNA vaccine served as the positive and negative control, respectively. Upon challenge with virulent Wa HRV, a significantly shortened duration and decreased severity of diarrhea and significant protection from virus shedding was induced by both mRNA vaccine candidates compared to the negative control. Both LS-P2-VP8* doses induced significantly higher VP8-specific IgG antibody titers in the serum after immunizations than the negative as well as the protein control. The P[8] VP8-specific IgG antibody-secreting cells in the ileum, spleen, and blood seven days post-challenge, as well as VP8-specific IFN-γ-producing T-cell numbers increased in all three mRNA-vaccinated pig groups compared to the negative control. Overall, there was a clear tendency towards improved responses in LS-P2-VP8 compared to the P2-VP8mRNA vaccine. The demonstrated strong humoral immune responses, priming for effector T cells, and the significant reduction of viral shedding and duration of diarrhea in Gn pigs provide a promising proof of concept and may provide guidance for the further development of mRNA-based rotavirus vaccines. rotavirus mRNA vaccine gnotobiotic pigs P2-VP8 diarrhea Medicine R Sandro Roier verfasserin aut Peng Zhou verfasserin aut Sofia Schnur verfasserin aut Charlotte Nyblade verfasserin aut Viviana Parreno verfasserin aut Annie Frazier verfasserin aut Maggie Frazier verfasserin aut Kelsey Kiley verfasserin aut Samantha O’Brien verfasserin aut Yu Liang verfasserin aut Bryan T. Mayer verfasserin aut Ruizhe Wu verfasserin aut Celia Mahoney verfasserin aut Monica M. McNeal verfasserin aut Benjamin Petsch verfasserin aut Susanne Rauch verfasserin aut Lijuan Yuan verfasserin aut In Vaccines MDPI AG, 2013 12(2024), 3, p 260 (DE-627)736559205 (DE-600)2703319-3 2076393X nnns volume:12 year:2024 number:3, p 260 https://doi.org/10.3390/vaccines12030260 kostenfrei https://doaj.org/article/cb5a7873ad0641e491f027758ab5b5e0 kostenfrei https://www.mdpi.com/2076-393X/12/3/260 kostenfrei https://doaj.org/toc/2076-393X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2024 3, p 260
language	English
source	In Vaccines 12(2024), 3, p 260 volume:12 year:2024 number:3, p 260
sourceStr	In Vaccines 12(2024), 3, p 260 volume:12 year:2024 number:3, p 260
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	rotavirus mRNA vaccine gnotobiotic pigs P2-VP8* diarrhea Medicine R
isfreeaccess_bool	true
container_title	Vaccines
authorswithroles_txt_mv	Casey Hensley @@aut@@ Sandro Roier @@aut@@ Peng Zhou @@aut@@ Sofia Schnur @@aut@@ Charlotte Nyblade @@aut@@ Viviana Parreno @@aut@@ Annie Frazier @@aut@@ Maggie Frazier @@aut@@ Kelsey Kiley @@aut@@ Samantha O’Brien @@aut@@ Yu Liang @@aut@@ Bryan T. Mayer @@aut@@ Ruizhe Wu @@aut@@ Celia Mahoney @@aut@@ Monica M. McNeal @@aut@@ Benjamin Petsch @@aut@@ Susanne Rauch @@aut@@ Lijuan Yuan @@aut@@
publishDateDaySort_date	2024-01-01T00:00:00Z
hierarchy_top_id	736559205
id	DOAJ099806223
language_de	englisch
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Previously, we demonstrated the immunogenicity of mRNA-based HRV vaccine candidates expressing the viral spike protein VP8* in rodent models. In the present study, we assessed the immunogenicity and protective efficacy of two mRNA-based HRV trivalent vaccine candidates, encoding VP8* of the genotypes P[8], P[6], or P[4], in the gnotobiotic (Gn) pig model of Wa (G1P[8]) HRV infection and diarrhea. Vaccines either encoded VP8* alone fused to the universal T-cell epitope P2 (P2-VP8) or expressed P2-VP8 as a fusion protein with lumazine synthase (LS-P2-VP8) to allow the formation and secretion of protein particles that present VP8 on their surface. Gn pigs were randomly assigned into groups and immunized three times with either P2-VP8* (30 µg) or LS-P2-VP8* (30 µg or 12 µg). A trivalent alum-adjuvanted P2-VP8* protein vaccine or an LNP-formulated irrelevant mRNA vaccine served as the positive and negative control, respectively. 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author	Casey Hensley
spellingShingle	Casey Hensley misc rotavirus misc mRNA vaccine misc gnotobiotic pigs misc P2-VP8* misc diarrhea misc Medicine misc R mRNA-Based Vaccines Are Highly Immunogenic and Confer Protection in the Gnotobiotic Pig Model of Human Rotavirus Diarrhea
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topic_title	mRNA-Based Vaccines Are Highly Immunogenic and Confer Protection in the Gnotobiotic Pig Model of Human Rotavirus Diarrhea rotavirus mRNA vaccine gnotobiotic pigs P2-VP8* diarrhea
topic	misc rotavirus misc mRNA vaccine misc gnotobiotic pigs misc P2-VP8* misc diarrhea misc Medicine misc R
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title	mRNA-Based Vaccines Are Highly Immunogenic and Confer Protection in the Gnotobiotic Pig Model of Human Rotavirus Diarrhea
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title_full	mRNA-Based Vaccines Are Highly Immunogenic and Confer Protection in the Gnotobiotic Pig Model of Human Rotavirus Diarrhea
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author_browse	Casey Hensley Sandro Roier Peng Zhou Sofia Schnur Charlotte Nyblade Viviana Parreno Annie Frazier Maggie Frazier Kelsey Kiley Samantha O’Brien Yu Liang Bryan T. Mayer Ruizhe Wu Celia Mahoney Monica M. McNeal Benjamin Petsch Susanne Rauch Lijuan Yuan
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title_sort	mrna-based vaccines are highly immunogenic and confer protection in the gnotobiotic pig model of human rotavirus diarrhea
title_auth	mRNA-Based Vaccines Are Highly Immunogenic and Confer Protection in the Gnotobiotic Pig Model of Human Rotavirus Diarrhea
abstract	Human rotavirus (HRV) is still a leading cause of severe dehydrating gastroenteritis globally, particularly in infants and children. Previously, we demonstrated the immunogenicity of mRNA-based HRV vaccine candidates expressing the viral spike protein VP8* in rodent models. In the present study, we assessed the immunogenicity and protective efficacy of two mRNA-based HRV trivalent vaccine candidates, encoding VP8* of the genotypes P[8], P[6], or P[4], in the gnotobiotic (Gn) pig model of Wa (G1P[8]) HRV infection and diarrhea. Vaccines either encoded VP8* alone fused to the universal T-cell epitope P2 (P2-VP8) or expressed P2-VP8 as a fusion protein with lumazine synthase (LS-P2-VP8) to allow the formation and secretion of protein particles that present VP8 on their surface. Gn pigs were randomly assigned into groups and immunized three times with either P2-VP8* (30 µg) or LS-P2-VP8* (30 µg or 12 µg). A trivalent alum-adjuvanted P2-VP8* protein vaccine or an LNP-formulated irrelevant mRNA vaccine served as the positive and negative control, respectively. Upon challenge with virulent Wa HRV, a significantly shortened duration and decreased severity of diarrhea and significant protection from virus shedding was induced by both mRNA vaccine candidates compared to the negative control. Both LS-P2-VP8* doses induced significantly higher VP8-specific IgG antibody titers in the serum after immunizations than the negative as well as the protein control. The P[8] VP8-specific IgG antibody-secreting cells in the ileum, spleen, and blood seven days post-challenge, as well as VP8-specific IFN-γ-producing T-cell numbers increased in all three mRNA-vaccinated pig groups compared to the negative control. Overall, there was a clear tendency towards improved responses in LS-P2-VP8 compared to the P2-VP8*mRNA vaccine. The demonstrated strong humoral immune responses, priming for effector T cells, and the significant reduction of viral shedding and duration of diarrhea in Gn pigs provide a promising proof of concept and may provide guidance for the further development of mRNA-based rotavirus vaccines.
abstractGer	Human rotavirus (HRV) is still a leading cause of severe dehydrating gastroenteritis globally, particularly in infants and children. Previously, we demonstrated the immunogenicity of mRNA-based HRV vaccine candidates expressing the viral spike protein VP8* in rodent models. In the present study, we assessed the immunogenicity and protective efficacy of two mRNA-based HRV trivalent vaccine candidates, encoding VP8* of the genotypes P[8], P[6], or P[4], in the gnotobiotic (Gn) pig model of Wa (G1P[8]) HRV infection and diarrhea. Vaccines either encoded VP8* alone fused to the universal T-cell epitope P2 (P2-VP8) or expressed P2-VP8 as a fusion protein with lumazine synthase (LS-P2-VP8) to allow the formation and secretion of protein particles that present VP8 on their surface. Gn pigs were randomly assigned into groups and immunized three times with either P2-VP8* (30 µg) or LS-P2-VP8* (30 µg or 12 µg). A trivalent alum-adjuvanted P2-VP8* protein vaccine or an LNP-formulated irrelevant mRNA vaccine served as the positive and negative control, respectively. Upon challenge with virulent Wa HRV, a significantly shortened duration and decreased severity of diarrhea and significant protection from virus shedding was induced by both mRNA vaccine candidates compared to the negative control. Both LS-P2-VP8* doses induced significantly higher VP8-specific IgG antibody titers in the serum after immunizations than the negative as well as the protein control. The P[8] VP8-specific IgG antibody-secreting cells in the ileum, spleen, and blood seven days post-challenge, as well as VP8-specific IFN-γ-producing T-cell numbers increased in all three mRNA-vaccinated pig groups compared to the negative control. Overall, there was a clear tendency towards improved responses in LS-P2-VP8 compared to the P2-VP8*mRNA vaccine. The demonstrated strong humoral immune responses, priming for effector T cells, and the significant reduction of viral shedding and duration of diarrhea in Gn pigs provide a promising proof of concept and may provide guidance for the further development of mRNA-based rotavirus vaccines.
abstract_unstemmed	Human rotavirus (HRV) is still a leading cause of severe dehydrating gastroenteritis globally, particularly in infants and children. Previously, we demonstrated the immunogenicity of mRNA-based HRV vaccine candidates expressing the viral spike protein VP8* in rodent models. In the present study, we assessed the immunogenicity and protective efficacy of two mRNA-based HRV trivalent vaccine candidates, encoding VP8* of the genotypes P[8], P[6], or P[4], in the gnotobiotic (Gn) pig model of Wa (G1P[8]) HRV infection and diarrhea. Vaccines either encoded VP8* alone fused to the universal T-cell epitope P2 (P2-VP8) or expressed P2-VP8 as a fusion protein with lumazine synthase (LS-P2-VP8) to allow the formation and secretion of protein particles that present VP8 on their surface. Gn pigs were randomly assigned into groups and immunized three times with either P2-VP8* (30 µg) or LS-P2-VP8* (30 µg or 12 µg). A trivalent alum-adjuvanted P2-VP8* protein vaccine or an LNP-formulated irrelevant mRNA vaccine served as the positive and negative control, respectively. Upon challenge with virulent Wa HRV, a significantly shortened duration and decreased severity of diarrhea and significant protection from virus shedding was induced by both mRNA vaccine candidates compared to the negative control. Both LS-P2-VP8* doses induced significantly higher VP8-specific IgG antibody titers in the serum after immunizations than the negative as well as the protein control. The P[8] VP8-specific IgG antibody-secreting cells in the ileum, spleen, and blood seven days post-challenge, as well as VP8-specific IFN-γ-producing T-cell numbers increased in all three mRNA-vaccinated pig groups compared to the negative control. Overall, there was a clear tendency towards improved responses in LS-P2-VP8 compared to the P2-VP8*mRNA vaccine. The demonstrated strong humoral immune responses, priming for effector T cells, and the significant reduction of viral shedding and duration of diarrhea in Gn pigs provide a promising proof of concept and may provide guidance for the further development of mRNA-based rotavirus vaccines.
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title_short	mRNA-Based Vaccines Are Highly Immunogenic and Confer Protection in the Gnotobiotic Pig Model of Human Rotavirus Diarrhea
url	https://doi.org/10.3390/vaccines12030260 https://doaj.org/article/cb5a7873ad0641e491f027758ab5b5e0 https://www.mdpi.com/2076-393X/12/3/260 https://doaj.org/toc/2076-393X
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mRNA-Based Vaccines Are Highly Immunogenic and Confer Protection in the Gnotobiotic Pig Model of Human Rotavirus Diarrhea

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