Immunogenicity and efficacy of VLA2001 vaccine against SARS-CoV-2 infection in male cynomolgus macaques
Abstract Background The fight against COVID-19 requires mass vaccination strategies, and vaccines inducing durable cross-protective responses are still needed. Inactivated vaccines have proven lasting efficacy against many pathogens and good safety records. They contain multiple protein antigens tha...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-04-01
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| Series: | Communications Medicine |
| Online Access: | https://doi.org/10.1038/s43856-024-00488-w |
| _version_ | 1827291406950989824 |
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| author | Mathilde Galhaut Urban Lundberg Romain Marlin Robert Schlegl Stefan Seidel Ursula Bartuschka Jürgen Heindl-Wruss Francis Relouzat Sébastien Langlois Nathalie Dereuddre-Bosquet Julie Morin Maxence Galpin-Lebreau Anne-Sophie Gallouët Wesley Gros Thibaut Naninck Quentin Pascal Catherine Chapon Karine Mouchain Guillaume Fichet Julien Lemaitre Mariangela Cavarelli Vanessa Contreras Nicolas Legrand Andreas Meinke Roger Le Grand |
| author_facet | Mathilde Galhaut Urban Lundberg Romain Marlin Robert Schlegl Stefan Seidel Ursula Bartuschka Jürgen Heindl-Wruss Francis Relouzat Sébastien Langlois Nathalie Dereuddre-Bosquet Julie Morin Maxence Galpin-Lebreau Anne-Sophie Gallouët Wesley Gros Thibaut Naninck Quentin Pascal Catherine Chapon Karine Mouchain Guillaume Fichet Julien Lemaitre Mariangela Cavarelli Vanessa Contreras Nicolas Legrand Andreas Meinke Roger Le Grand |
| author_sort | Mathilde Galhaut |
| collection | DOAJ |
| description | Abstract Background The fight against COVID-19 requires mass vaccination strategies, and vaccines inducing durable cross-protective responses are still needed. Inactivated vaccines have proven lasting efficacy against many pathogens and good safety records. They contain multiple protein antigens that may improve response breadth and can be easily adapted every year to maintain preparedness for future seasonally emerging variants. Methods The vaccine dose was determined using ELISA and pseudoviral particle-based neutralization assay in the mice. The immunogenicity was assessed in the non-human primates with multiplex ELISA, neutralization assays, ELISpot and intracellular staining. The efficacy was demonstrated by viral quantification in fluids using RT-qPCR and respiratory tissue lesions evaluation. Results Here we report the immunogenicity and efficacy of VLA2001 in animal models. VLA2001 formulated with alum and the TLR9 agonist CpG 1018™ adjuvant generate a Th1-biased immune response and serum neutralizing antibodies in female BALB/c mice. In male cynomolgus macaques, two injections of VLA2001 are sufficient to induce specific and polyfunctional CD4+ T cell responses, predominantly Th1-biased, and high levels of antibodies neutralizing SARS-CoV-2 infection in cell culture. These antibodies also inhibit the binding of the Spike protein to human ACE2 receptor of several variants of concern most resistant to neutralization. After exposure to a high dose of homologous SARS-CoV-2, vaccinated groups exhibit significant levels of protection from viral replication in the upper and lower respiratory tracts and from lung tissue inflammation. Conclusions We demonstrate that the VLA2001 adjuvanted vaccine is immunogenic both in mouse and NHP models and prevent cynomolgus macaques from the viruses responsible of COVID-19. |
| first_indexed | 2024-04-24T12:36:29Z |
| format | Article |
| id | doaj.art-b20cf0b0a10841d78b8331ab24c32b42 |
| institution | Directory Open Access Journal |
| issn | 2730-664X |
| language | English |
| last_indexed | 2024-04-24T12:36:29Z |
| publishDate | 2024-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Medicine |
| spelling | doaj.art-b20cf0b0a10841d78b8331ab24c32b422024-04-07T11:28:26ZengNature PortfolioCommunications Medicine2730-664X2024-04-014111110.1038/s43856-024-00488-wImmunogenicity and efficacy of VLA2001 vaccine against SARS-CoV-2 infection in male cynomolgus macaquesMathilde Galhaut0Urban Lundberg1Romain Marlin2Robert Schlegl3Stefan Seidel4Ursula Bartuschka5Jürgen Heindl-Wruss6Francis Relouzat7Sébastien Langlois8Nathalie Dereuddre-Bosquet9Julie Morin10Maxence Galpin-Lebreau11Anne-Sophie Gallouët12Wesley Gros13Thibaut Naninck14Quentin Pascal15Catherine Chapon16Karine Mouchain17Guillaume Fichet18Julien Lemaitre19Mariangela Cavarelli20Vanessa Contreras21Nicolas Legrand22Andreas Meinke23Roger Le Grand24Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEAVALNEVA Austria GmbHCenter for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEAVALNEVA Austria GmbHVALNEVA Austria GmbHVALNEVA Austria GmbHVALNEVA Austria GmbHCenter for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEACenter for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEACenter for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEACenter for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEACenter for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEACenter for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEACenter for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEACenter for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEACenter for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEACenter for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEAONCODESIGN SERVICES, François Hyafil Research CenterONCODESIGN SERVICES, François Hyafil Research CenterCenter for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEACenter for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEACenter for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEAONCODESIGN SERVICES, François Hyafil Research CenterVALNEVA Austria GmbHCenter for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEAAbstract Background The fight against COVID-19 requires mass vaccination strategies, and vaccines inducing durable cross-protective responses are still needed. Inactivated vaccines have proven lasting efficacy against many pathogens and good safety records. They contain multiple protein antigens that may improve response breadth and can be easily adapted every year to maintain preparedness for future seasonally emerging variants. Methods The vaccine dose was determined using ELISA and pseudoviral particle-based neutralization assay in the mice. The immunogenicity was assessed in the non-human primates with multiplex ELISA, neutralization assays, ELISpot and intracellular staining. The efficacy was demonstrated by viral quantification in fluids using RT-qPCR and respiratory tissue lesions evaluation. Results Here we report the immunogenicity and efficacy of VLA2001 in animal models. VLA2001 formulated with alum and the TLR9 agonist CpG 1018™ adjuvant generate a Th1-biased immune response and serum neutralizing antibodies in female BALB/c mice. In male cynomolgus macaques, two injections of VLA2001 are sufficient to induce specific and polyfunctional CD4+ T cell responses, predominantly Th1-biased, and high levels of antibodies neutralizing SARS-CoV-2 infection in cell culture. These antibodies also inhibit the binding of the Spike protein to human ACE2 receptor of several variants of concern most resistant to neutralization. After exposure to a high dose of homologous SARS-CoV-2, vaccinated groups exhibit significant levels of protection from viral replication in the upper and lower respiratory tracts and from lung tissue inflammation. Conclusions We demonstrate that the VLA2001 adjuvanted vaccine is immunogenic both in mouse and NHP models and prevent cynomolgus macaques from the viruses responsible of COVID-19.https://doi.org/10.1038/s43856-024-00488-w |
| spellingShingle | Mathilde Galhaut Urban Lundberg Romain Marlin Robert Schlegl Stefan Seidel Ursula Bartuschka Jürgen Heindl-Wruss Francis Relouzat Sébastien Langlois Nathalie Dereuddre-Bosquet Julie Morin Maxence Galpin-Lebreau Anne-Sophie Gallouët Wesley Gros Thibaut Naninck Quentin Pascal Catherine Chapon Karine Mouchain Guillaume Fichet Julien Lemaitre Mariangela Cavarelli Vanessa Contreras Nicolas Legrand Andreas Meinke Roger Le Grand Immunogenicity and efficacy of VLA2001 vaccine against SARS-CoV-2 infection in male cynomolgus macaques Communications Medicine |
| title | Immunogenicity and efficacy of VLA2001 vaccine against SARS-CoV-2 infection in male cynomolgus macaques |
| title_full | Immunogenicity and efficacy of VLA2001 vaccine against SARS-CoV-2 infection in male cynomolgus macaques |
| title_fullStr | Immunogenicity and efficacy of VLA2001 vaccine against SARS-CoV-2 infection in male cynomolgus macaques |
| title_full_unstemmed | Immunogenicity and efficacy of VLA2001 vaccine against SARS-CoV-2 infection in male cynomolgus macaques |
| title_short | Immunogenicity and efficacy of VLA2001 vaccine against SARS-CoV-2 infection in male cynomolgus macaques |
| title_sort | immunogenicity and efficacy of vla2001 vaccine against sars cov 2 infection in male cynomolgus macaques |
| url | https://doi.org/10.1038/s43856-024-00488-w |
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