A Lassa virus mRNA vaccine confers protection but does not require neutralizing antibody in a guinea pig model of infection
Abstract Lassa virus is a member of the Arenaviridae family, which causes human infections ranging from asymptomatic to severe hemorrhagic disease with a high case fatality rate. We have designed and generated lipid nanoparticle encapsulated, modified mRNA vaccines that encode for the wild-type Lass...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-09-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-41376-6 |
| _version_ | 1797558577719672832 |
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| author | Adam J. Ronk Nicole M. Lloyd Min Zhang Caroline Atyeo Hailee R. Perrett Chad E. Mire Kathryn M. Hastie Rogier W. Sanders Philip J. M. Brouwer Erica Olmann Saphire Andrew B. Ward Thomas G. Ksiazek Juan Carlos Alvarez Moreno Harshwardhan M. Thaker Galit Alter Sunny Himansu Andrea Carfi Alexander Bukreyev |
| author_facet | Adam J. Ronk Nicole M. Lloyd Min Zhang Caroline Atyeo Hailee R. Perrett Chad E. Mire Kathryn M. Hastie Rogier W. Sanders Philip J. M. Brouwer Erica Olmann Saphire Andrew B. Ward Thomas G. Ksiazek Juan Carlos Alvarez Moreno Harshwardhan M. Thaker Galit Alter Sunny Himansu Andrea Carfi Alexander Bukreyev |
| author_sort | Adam J. Ronk |
| collection | DOAJ |
| description | Abstract Lassa virus is a member of the Arenaviridae family, which causes human infections ranging from asymptomatic to severe hemorrhagic disease with a high case fatality rate. We have designed and generated lipid nanoparticle encapsulated, modified mRNA vaccines that encode for the wild-type Lassa virus strain Josiah glycoprotein complex or the prefusion stabilized conformation of the Lassa virus glycoprotein complex. Hartley guinea pigs were vaccinated with two 10 µg doses, 28 days apart, of either construct. Vaccination induced strong binding antibody responses, specific to the prefusion conformation of glycoprotein complex, which were significantly higher in the prefusion stabilized glycoprotein complex construct group and displayed strong Fc-mediated effects. However, Lassa virus-neutralizing antibody activity was detected in some but not all animals. Following the challenge with a lethal dose of the Lassa virus, all vaccinated animals were protected from death and severe disease. Although the definitive mechanism of protection is still unknown, and assessment of the cell-mediated immune response was not investigated in this study, these data demonstrate the promise of mRNA as a vaccine platform against the Lassa virus and that protection against Lassa virus can be achieved in the absence of virus-neutralizing antibodies. |
| first_indexed | 2024-03-10T17:33:30Z |
| format | Article |
| id | doaj.art-4afd193033d54672afc7fc5b00f7b333 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-10T17:33:30Z |
| publishDate | 2023-09-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-4afd193033d54672afc7fc5b00f7b3332023-11-20T09:56:56ZengNature PortfolioNature Communications2041-17232023-09-0114111310.1038/s41467-023-41376-6A Lassa virus mRNA vaccine confers protection but does not require neutralizing antibody in a guinea pig model of infectionAdam J. Ronk0Nicole M. Lloyd1Min Zhang2Caroline Atyeo3Hailee R. Perrett4Chad E. Mire5Kathryn M. Hastie6Rogier W. Sanders7Philip J. M. Brouwer8Erica Olmann Saphire9Andrew B. Ward10Thomas G. Ksiazek11Juan Carlos Alvarez Moreno12Harshwardhan M. Thaker13Galit Alter14Sunny Himansu15Andrea Carfi16Alexander Bukreyev17Department of Pathology, University of Texas Medical BranchDepartment of Pathology, University of Texas Medical BranchDepartment of Pathology, University of Texas Medical BranchDepartment of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public HealthDepartment of Integrative Structural and Computational Biology California Campus, Scripps ResearchGalveston National Laboratory, University of Texas Medical BranchCenter for Infectious Disease and Vaccine Research, La Jolla Institute for ImmunologyDepartment of Medical Microbiology, Academic Medical CenterDepartment of Medical Microbiology, Academic Medical CenterCenter for Infectious Disease and Vaccine Research, La Jolla Institute for ImmunologyDepartment of Integrative Structural and Computational Biology California Campus, Scripps ResearchDepartment of Pathology, University of Texas Medical BranchDepartment of Pathology, University of Texas Medical BranchDepartment of Pathology, University of Texas Medical BranchDepartment of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public HealthModerna, IncModerna, IncDepartment of Pathology, University of Texas Medical BranchAbstract Lassa virus is a member of the Arenaviridae family, which causes human infections ranging from asymptomatic to severe hemorrhagic disease with a high case fatality rate. We have designed and generated lipid nanoparticle encapsulated, modified mRNA vaccines that encode for the wild-type Lassa virus strain Josiah glycoprotein complex or the prefusion stabilized conformation of the Lassa virus glycoprotein complex. Hartley guinea pigs were vaccinated with two 10 µg doses, 28 days apart, of either construct. Vaccination induced strong binding antibody responses, specific to the prefusion conformation of glycoprotein complex, which were significantly higher in the prefusion stabilized glycoprotein complex construct group and displayed strong Fc-mediated effects. However, Lassa virus-neutralizing antibody activity was detected in some but not all animals. Following the challenge with a lethal dose of the Lassa virus, all vaccinated animals were protected from death and severe disease. Although the definitive mechanism of protection is still unknown, and assessment of the cell-mediated immune response was not investigated in this study, these data demonstrate the promise of mRNA as a vaccine platform against the Lassa virus and that protection against Lassa virus can be achieved in the absence of virus-neutralizing antibodies.https://doi.org/10.1038/s41467-023-41376-6 |
| spellingShingle | Adam J. Ronk Nicole M. Lloyd Min Zhang Caroline Atyeo Hailee R. Perrett Chad E. Mire Kathryn M. Hastie Rogier W. Sanders Philip J. M. Brouwer Erica Olmann Saphire Andrew B. Ward Thomas G. Ksiazek Juan Carlos Alvarez Moreno Harshwardhan M. Thaker Galit Alter Sunny Himansu Andrea Carfi Alexander Bukreyev A Lassa virus mRNA vaccine confers protection but does not require neutralizing antibody in a guinea pig model of infection Nature Communications |
| title | A Lassa virus mRNA vaccine confers protection but does not require neutralizing antibody in a guinea pig model of infection |
| title_full | A Lassa virus mRNA vaccine confers protection but does not require neutralizing antibody in a guinea pig model of infection |
| title_fullStr | A Lassa virus mRNA vaccine confers protection but does not require neutralizing antibody in a guinea pig model of infection |
| title_full_unstemmed | A Lassa virus mRNA vaccine confers protection but does not require neutralizing antibody in a guinea pig model of infection |
| title_short | A Lassa virus mRNA vaccine confers protection but does not require neutralizing antibody in a guinea pig model of infection |
| title_sort | lassa virus mrna vaccine confers protection but does not require neutralizing antibody in a guinea pig model of infection |
| url | https://doi.org/10.1038/s41467-023-41376-6 |
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