Metavac-RSV mucosal bivalent vaccine candidate protects cotton rats against pneumoviruses and is produced using serum-free cell culture in bioreactor
Abstract Respiratory syncytial virus (RSV) and human metapneumovirus (HMPV) are the main etiologic agents of viral bronchiolitis and pneumonia in children and the elderly. As live-attenuated vaccines (LAV) can stimulate robust mucosal and cellular responses, we previously engineered an HMPV-based bi...
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Nature Portfolio
2025-08-01
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| Series: | npj Vaccines |
| Online Access: | https://doi.org/10.1038/s41541-025-01231-9 |
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| author | Caroline Chupin Pauline Brun Marjorie Ray Chloé Mialon Maëlle Reitano Aurélien Traversier Emilie Laurent Abdelghafar Goumaidi Julien Fouret Stéphane Paul Marina Boukhvalova Kevin Yim Jorge Blanco Marie-Eve Hamelin Guy Boivin Manuel Rosa-Calatrava Julia Dubois |
| author_facet | Caroline Chupin Pauline Brun Marjorie Ray Chloé Mialon Maëlle Reitano Aurélien Traversier Emilie Laurent Abdelghafar Goumaidi Julien Fouret Stéphane Paul Marina Boukhvalova Kevin Yim Jorge Blanco Marie-Eve Hamelin Guy Boivin Manuel Rosa-Calatrava Julia Dubois |
| author_sort | Caroline Chupin |
| collection | DOAJ |
| description | Abstract Respiratory syncytial virus (RSV) and human metapneumovirus (HMPV) are the main etiologic agents of viral bronchiolitis and pneumonia in children and the elderly. As live-attenuated vaccines (LAV) can stimulate robust mucosal and cellular responses, we previously engineered an HMPV-based bivalent LAV Metavac®-RSV candidate and reported its capacity to protect mice against HMPV and RSV challenges after intranasal delivery. To progress towards clinical development, we identified a GMP-grade Vero cell platform as permissive and efficient to produce high yields of functional Metavac®-RSV, expressing both RSV and HMPV F antigen after several passages. Metavac®-RSV protected cotton rats against both HMPV and RSV challenges, significantly reducing viral replication in the respiratory airways and inducing high titers of neutralizing antibodies. Finally, we identified process parameters to scale-up the production process of Metavac®-RSV using Vero cells cultivated on microcarriers in a 2 L single-use stirred-tank bioreactor, with a scalable upstream production process amenable to industrial manufacturing. |
| format | Article |
| id | doaj-art-3037dbde96fc4d34a3edbe7bbdf26309 |
| institution | Kabale University |
| issn | 2059-0105 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Vaccines |
| spelling | doaj-art-3037dbde96fc4d34a3edbe7bbdf263092025-08-24T11:06:34ZengNature Portfolionpj Vaccines2059-01052025-08-0110111510.1038/s41541-025-01231-9Metavac-RSV mucosal bivalent vaccine candidate protects cotton rats against pneumoviruses and is produced using serum-free cell culture in bioreactorCaroline Chupin0Pauline Brun1Marjorie Ray2Chloé Mialon3Maëlle Reitano4Aurélien Traversier5Emilie Laurent6Abdelghafar Goumaidi7Julien Fouret8Stéphane Paul9Marina Boukhvalova10Kevin Yim11Jorge Blanco12Marie-Eve Hamelin13Guy Boivin14Manuel Rosa-Calatrava15Julia Dubois16International Research Laboratory RESPIVIR France - Canada, Centre Hospitalier Universitaire de Québec-Université Laval, Québec, Canada ; Centre International de Recherche en Infectiologie, Faculté de Médecine RTH Laennec, Université Claude Bernard Lyon 1, Université de Lyon, INSERM, CNRS, ENS de LyonInternational Research Laboratory RESPIVIR France - Canada, Centre Hospitalier Universitaire de Québec-Université Laval, Québec, Canada ; Centre International de Recherche en Infectiologie, Faculté de Médecine RTH Laennec, Université Claude Bernard Lyon 1, Université de Lyon, INSERM, CNRS, ENS de LyonVaxxel, 43 Boulevard du onze novembre 1918International Research Laboratory RESPIVIR France - Canada, Centre Hospitalier Universitaire de Québec-Université Laval, Québec, Canada ; Centre International de Recherche en Infectiologie, Faculté de Médecine RTH Laennec, Université Claude Bernard Lyon 1, Université de Lyon, INSERM, CNRS, ENS de LyonInternational Research Laboratory RESPIVIR France - Canada, Centre Hospitalier Universitaire de Québec-Université Laval, Québec, Canada ; Centre International de Recherche en Infectiologie, Faculté de Médecine RTH Laennec, Université Claude Bernard Lyon 1, Université de Lyon, INSERM, CNRS, ENS de LyonInternational Research Laboratory RESPIVIR France - Canada, Centre Hospitalier Universitaire de Québec-Université Laval, Québec, Canada ; Centre International de Recherche en Infectiologie, Faculté de Médecine RTH Laennec, Université Claude Bernard Lyon 1, Université de Lyon, INSERM, CNRS, ENS de LyonInternational Research Laboratory RESPIVIR France - Canada, Centre Hospitalier Universitaire de Québec-Université Laval, Québec, Canada ; Centre International de Recherche en Infectiologie, Faculté de Médecine RTH Laennec, Université Claude Bernard Lyon 1, Université de Lyon, INSERM, CNRS, ENS de LyonNexomis, Faculté de Médecine RTH Laennec, Université Claude Bernard Lyon 1, Université de LyonInternational Research Laboratory RESPIVIR France - Canada, Centre Hospitalier Universitaire de Québec-Université Laval, Québec, Canada ; Centre International de Recherche en Infectiologie, Faculté de Médecine RTH Laennec, Université Claude Bernard Lyon 1, Université de Lyon, INSERM, CNRS, ENS de LyonCIRI, Centre International de Recherche en Infectiologie, Team GIMAP, Université Claude Bernard Lyon 1, INSERM U1111, CNRS UMR5308, ENS Lyon, Université Jean Monnet Saint-EtienneSigmovir Biosystems, Inc.Sigmovir Biosystems, Inc.Sigmovir Biosystems, Inc.International Research Laboratory RESPIVIR France - Canada, Centre Hospitalier Universitaire de Québec-Université Laval, Québec, Canada ; Centre International de Recherche en Infectiologie, Faculté de Médecine RTH Laennec, Université Claude Bernard Lyon 1, Université de Lyon, INSERM, CNRS, ENS de LyonInternational Research Laboratory RESPIVIR France - Canada, Centre Hospitalier Universitaire de Québec-Université Laval, Québec, Canada ; Centre International de Recherche en Infectiologie, Faculté de Médecine RTH Laennec, Université Claude Bernard Lyon 1, Université de Lyon, INSERM, CNRS, ENS de LyonInternational Research Laboratory RESPIVIR France - Canada, Centre Hospitalier Universitaire de Québec-Université Laval, Québec, Canada ; Centre International de Recherche en Infectiologie, Faculté de Médecine RTH Laennec, Université Claude Bernard Lyon 1, Université de Lyon, INSERM, CNRS, ENS de LyonInternational Research Laboratory RESPIVIR France - Canada, Centre Hospitalier Universitaire de Québec-Université Laval, Québec, Canada ; Centre International de Recherche en Infectiologie, Faculté de Médecine RTH Laennec, Université Claude Bernard Lyon 1, Université de Lyon, INSERM, CNRS, ENS de LyonAbstract Respiratory syncytial virus (RSV) and human metapneumovirus (HMPV) are the main etiologic agents of viral bronchiolitis and pneumonia in children and the elderly. As live-attenuated vaccines (LAV) can stimulate robust mucosal and cellular responses, we previously engineered an HMPV-based bivalent LAV Metavac®-RSV candidate and reported its capacity to protect mice against HMPV and RSV challenges after intranasal delivery. To progress towards clinical development, we identified a GMP-grade Vero cell platform as permissive and efficient to produce high yields of functional Metavac®-RSV, expressing both RSV and HMPV F antigen after several passages. Metavac®-RSV protected cotton rats against both HMPV and RSV challenges, significantly reducing viral replication in the respiratory airways and inducing high titers of neutralizing antibodies. Finally, we identified process parameters to scale-up the production process of Metavac®-RSV using Vero cells cultivated on microcarriers in a 2 L single-use stirred-tank bioreactor, with a scalable upstream production process amenable to industrial manufacturing.https://doi.org/10.1038/s41541-025-01231-9 |
| spellingShingle | Caroline Chupin Pauline Brun Marjorie Ray Chloé Mialon Maëlle Reitano Aurélien Traversier Emilie Laurent Abdelghafar Goumaidi Julien Fouret Stéphane Paul Marina Boukhvalova Kevin Yim Jorge Blanco Marie-Eve Hamelin Guy Boivin Manuel Rosa-Calatrava Julia Dubois Metavac-RSV mucosal bivalent vaccine candidate protects cotton rats against pneumoviruses and is produced using serum-free cell culture in bioreactor npj Vaccines |
| title | Metavac-RSV mucosal bivalent vaccine candidate protects cotton rats against pneumoviruses and is produced using serum-free cell culture in bioreactor |
| title_full | Metavac-RSV mucosal bivalent vaccine candidate protects cotton rats against pneumoviruses and is produced using serum-free cell culture in bioreactor |
| title_fullStr | Metavac-RSV mucosal bivalent vaccine candidate protects cotton rats against pneumoviruses and is produced using serum-free cell culture in bioreactor |
| title_full_unstemmed | Metavac-RSV mucosal bivalent vaccine candidate protects cotton rats against pneumoviruses and is produced using serum-free cell culture in bioreactor |
| title_short | Metavac-RSV mucosal bivalent vaccine candidate protects cotton rats against pneumoviruses and is produced using serum-free cell culture in bioreactor |
| title_sort | metavac rsv mucosal bivalent vaccine candidate protects cotton rats against pneumoviruses and is produced using serum free cell culture in bioreactor |
| url | https://doi.org/10.1038/s41541-025-01231-9 |
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