Lipid nanoparticle delivery of unmodified mRNAs encoding multiple monoclonal antibodies targeting poxviruses in rabbits
Poxviruses are a large and complex family of viruses with members such as monkeypox virus and variola virus. The possibility of an outbreak of monkeypox virus (or a related poxvirus) or the misuse of variola virus justifies the development of countermeasures. Furthermore, poxviruses can be a useful...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-06-01
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| Series: | Molecular Therapy: Nucleic Acids |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S216225312200138X |
| _version_ | 1811256183604903936 |
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| author | Eric M. Mucker Carolin Thiele-Suess Patrick Baumhof Jay W. Hooper |
| author_facet | Eric M. Mucker Carolin Thiele-Suess Patrick Baumhof Jay W. Hooper |
| author_sort | Eric M. Mucker |
| collection | DOAJ |
| description | Poxviruses are a large and complex family of viruses with members such as monkeypox virus and variola virus. The possibility of an outbreak of monkeypox virus (or a related poxvirus) or the misuse of variola virus justifies the development of countermeasures. Furthermore, poxviruses can be a useful surrogate for developing technology involving antibody therapies. In our experiments, we explored the feasibility of utilizing unmodified mRNA that encodes three previously described monoclonal antibodies, c8A, c6C, and c7D11, as countermeasures to smallpox in a relatively large (>3 kg) laboratory animal (rabbits). We confirmed in vitro translation, secretion, and biological activity of mRNA constructs and identified target monoclonal antibody levels from a murine vaccinia virus model that provided a clinical benefit. Individually, we were able to detect c7D11, c8A, and c6C in the serum of rabbits within 1 day of an intramuscular jet injection of lipid nanoparticle (LNP)-formulated mRNA. Injection of a combination of three LNP-formulated mRNA constructs encoding the three different antibodies produced near equivalent serum levels compared with each individual construct administered alone. These data are among the first demonstrating the feasibility of launching multiple antibodies using mRNA constructs in a large, nonrodent species. Based on empirically derived target serum level and the observed decay rate, the antibody levels attained were unlikely to provide protection. |
| first_indexed | 2024-04-12T17:36:16Z |
| format | Article |
| id | doaj.art-eab0acecfcea4c89975eb47a9a6c4539 |
| institution | Directory Open Access Journal |
| issn | 2162-2531 |
| language | English |
| last_indexed | 2024-04-12T17:36:16Z |
| publishDate | 2022-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Nucleic Acids |
| spelling | doaj.art-eab0acecfcea4c89975eb47a9a6c45392022-12-22T03:22:59ZengElsevierMolecular Therapy: Nucleic Acids2162-25312022-06-0128847858Lipid nanoparticle delivery of unmodified mRNAs encoding multiple monoclonal antibodies targeting poxviruses in rabbitsEric M. Mucker0Carolin Thiele-Suess1Patrick Baumhof2Jay W. Hooper3Virology Division, United States Army Medical Institute of Infectious Diseases, Fort Detrick, MD 21702, USACureVac, 72076 Tübingen, GermanyCureVac, 72076 Tübingen, GermanyVirology Division, United States Army Medical Institute of Infectious Diseases, Fort Detrick, MD 21702, USA; Corresponding author Jay W. Hooper, PhD, Virology Division, United States Army Medical Institute of Infectious Diseases, Fort Detrick, MD 21702, USA.Poxviruses are a large and complex family of viruses with members such as monkeypox virus and variola virus. The possibility of an outbreak of monkeypox virus (or a related poxvirus) or the misuse of variola virus justifies the development of countermeasures. Furthermore, poxviruses can be a useful surrogate for developing technology involving antibody therapies. In our experiments, we explored the feasibility of utilizing unmodified mRNA that encodes three previously described monoclonal antibodies, c8A, c6C, and c7D11, as countermeasures to smallpox in a relatively large (>3 kg) laboratory animal (rabbits). We confirmed in vitro translation, secretion, and biological activity of mRNA constructs and identified target monoclonal antibody levels from a murine vaccinia virus model that provided a clinical benefit. Individually, we were able to detect c7D11, c8A, and c6C in the serum of rabbits within 1 day of an intramuscular jet injection of lipid nanoparticle (LNP)-formulated mRNA. Injection of a combination of three LNP-formulated mRNA constructs encoding the three different antibodies produced near equivalent serum levels compared with each individual construct administered alone. These data are among the first demonstrating the feasibility of launching multiple antibodies using mRNA constructs in a large, nonrodent species. Based on empirically derived target serum level and the observed decay rate, the antibody levels attained were unlikely to provide protection.http://www.sciencedirect.com/science/article/pii/S216225312200138XMT: Delivery strategiesRNAmonoclonal antibodiesnucleic acidneutralizing antibodyrabbits |
| spellingShingle | Eric M. Mucker Carolin Thiele-Suess Patrick Baumhof Jay W. Hooper Lipid nanoparticle delivery of unmodified mRNAs encoding multiple monoclonal antibodies targeting poxviruses in rabbits Molecular Therapy: Nucleic Acids MT: Delivery strategies RNA monoclonal antibodies nucleic acid neutralizing antibody rabbits |
| title | Lipid nanoparticle delivery of unmodified mRNAs encoding multiple monoclonal antibodies targeting poxviruses in rabbits |
| title_full | Lipid nanoparticle delivery of unmodified mRNAs encoding multiple monoclonal antibodies targeting poxviruses in rabbits |
| title_fullStr | Lipid nanoparticle delivery of unmodified mRNAs encoding multiple monoclonal antibodies targeting poxviruses in rabbits |
| title_full_unstemmed | Lipid nanoparticle delivery of unmodified mRNAs encoding multiple monoclonal antibodies targeting poxviruses in rabbits |
| title_short | Lipid nanoparticle delivery of unmodified mRNAs encoding multiple monoclonal antibodies targeting poxviruses in rabbits |
| title_sort | lipid nanoparticle delivery of unmodified mrnas encoding multiple monoclonal antibodies targeting poxviruses in rabbits |
| topic | MT: Delivery strategies RNA monoclonal antibodies nucleic acid neutralizing antibody rabbits |
| url | http://www.sciencedirect.com/science/article/pii/S216225312200138X |
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