mRNA mediates passive vaccination against infectious agents, toxins, and tumors

Abstract 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 stud...

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Main Authors: Moritz Thran, Jean Mukherjee, Marion Pönisch, Katja Fiedler, Andreas Thess, Barbara L Mui, Michael J Hope, Ying K Tam, Nigel Horscroft, Regina Heidenreich, Mariola Fotin‐Mleczek, Charles B Shoemaker, Thomas Schlake
Format: Article
Language:English
Published: Springer Nature 2017-08-01
Series:EMBO Molecular Medicine
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Online Access:https://doi.org/10.15252/emmm.201707678
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author Moritz Thran
Jean Mukherjee
Marion Pönisch
Katja Fiedler
Andreas Thess
Barbara L Mui
Michael J Hope
Ying K Tam
Nigel Horscroft
Regina Heidenreich
Mariola Fotin‐Mleczek
Charles B Shoemaker
Thomas Schlake
author_facet Moritz Thran
Jean Mukherjee
Marion Pönisch
Katja Fiedler
Andreas Thess
Barbara L Mui
Michael J Hope
Ying K Tam
Nigel Horscroft
Regina Heidenreich
Mariola Fotin‐Mleczek
Charles B Shoemaker
Thomas Schlake
author_sort Moritz Thran
collection DOAJ
description Abstract 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.
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institution Kabale University
issn 1757-4676
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publishDate 2017-08-01
publisher Springer Nature
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series EMBO Molecular Medicine
spelling doaj-art-e38e62606e0c43b694eb441946af61b32025-08-20T04:03:07ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842017-08-019101434144710.15252/emmm.201707678mRNA mediates passive vaccination against infectious agents, toxins, and tumorsMoritz Thran0Jean Mukherjee1Marion Pönisch2Katja Fiedler3Andreas Thess4Barbara L Mui5Michael J Hope6Ying K Tam7Nigel Horscroft8Regina Heidenreich9Mariola Fotin‐Mleczek10Charles B Shoemaker11Thomas Schlake12CureVac AGDepartment of Infectious Disease and Global Health, Tufts Cummings School of Veterinary MedicineCureVac AGCureVac AGCureVac AGAcuitas TherapeuticsAcuitas TherapeuticsAcuitas TherapeuticsCureVac AGCureVac AGCureVac AGDepartment of Infectious Disease and Global Health, Tufts Cummings School of Veterinary MedicineCureVac AGAbstract 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.https://doi.org/10.15252/emmm.201707678antibodylipid nanoparticlemessenger RNAmousepassive immunization
spellingShingle Moritz Thran
Jean Mukherjee
Marion Pönisch
Katja Fiedler
Andreas Thess
Barbara L Mui
Michael J Hope
Ying K Tam
Nigel Horscroft
Regina Heidenreich
Mariola Fotin‐Mleczek
Charles B Shoemaker
Thomas Schlake
mRNA mediates passive vaccination against infectious agents, toxins, and tumors
EMBO Molecular Medicine
antibody
lipid nanoparticle
messenger RNA
mouse
passive immunization
title mRNA mediates passive vaccination against infectious agents, toxins, and tumors
title_full mRNA mediates passive vaccination against infectious agents, toxins, and tumors
title_fullStr mRNA mediates passive vaccination against infectious agents, toxins, and tumors
title_full_unstemmed mRNA mediates passive vaccination against infectious agents, toxins, and tumors
title_short mRNA mediates passive vaccination against infectious agents, toxins, and tumors
title_sort mrna mediates passive vaccination against infectious agents toxins and tumors
topic antibody
lipid nanoparticle
messenger RNA
mouse
passive immunization
url https://doi.org/10.15252/emmm.201707678
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