mRNA mediates passive vaccination against infectious agents, toxins, and tumors
| Autor: | Charles B. Shoemaker, Regina Heidenreich, Thomas Schlake, Ying K. Tam, Barbara L. Mui, Mariola Fotin-Mleczek, Michael J. Hope, Marion Pönisch, Moritz Thran, Nigel Horscroft, Andreas Thess, Katja Fiedler, Jean Mukherjee |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Rabies Immunology Dose-Response Relationship Immunologic Antibodies Viral Botulinum Antitoxin 03 medical and health sciences Therapeutic approach Mice 0302 clinical medicine Immune system antibody medicine Animals Humans RNA Messenger Research Articles mouse Messenger RNA Mice Inbred BALB C biology messenger RNA Immunization Passive Botulism medicine.disease lipid nanoparticle Microbiology Virology & Host Pathogen Interaction Vaccination Titer 030104 developmental biology Immunization Rabies Vaccines Rabies virus 030220 oncology & carcinogenesis biology.protein Molecular Medicine Nanoparticles passive immunization Female Antibody Post-Exposure Prophylaxis Research Article |
| Zdroj: | EMBO Molecular Medicine |
| ISSN: | 1757-4684 1757-4676 |
| Popis: | The delivery of genetic information has emerged as a valid therapeutic approach. Various reports have demonstrated that mRNA, besides its remarkable potential as vaccine, can also promote expression without inducing an adverse immune response against the encoded protein. In the current study, we set out to explore whether our technology based on chemically unmodified mRNA is suitable for passive immunization. To this end, various antibodies using different designs were expressed and characterized in vitro and in vivo in the fields of viral infections, toxin exposure, and cancer immunotherapies. Single injections of mRNA–lipid nanoparticle (LNP) were sufficient to establish rapid, strong, and long‐lasting serum antibody titers in vivo , thereby enabling both prophylactic and therapeutic protection against lethal rabies infection or botulinum intoxication. Moreover, therapeutic mRNA‐mediated antibody expression allowed mice to survive an otherwise lethal tumor challenge. In conclusion, the present study demonstrates the utility of formulated mRNA as a potent novel technology for passive immunization. |
| Databáze: | OpenAIRE |
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