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

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...

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Autores principales: Thran, Moritz, Mukherjee, Jean, Pönisch, Marion, Fiedler, Katja, Thess, Andreas, Mui, Barbara L, Hope, Michael J, Tam, Ying K, Horscroft, Nigel, Heidenreich, Regina, Fotin‐Mleczek, Mariola, Shoemaker, Charles B, Schlake, Thomas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5623855/
https://www.ncbi.nlm.nih.gov/pubmed/28794134
http://dx.doi.org/10.15252/emmm.201707678
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author Thran, Moritz
Mukherjee, Jean
Pönisch, Marion
Fiedler, Katja
Thess, Andreas
Mui, Barbara L
Hope, Michael J
Tam, Ying K
Horscroft, Nigel
Heidenreich, Regina
Fotin‐Mleczek, Mariola
Shoemaker, Charles B
Schlake, Thomas
author_facet Thran, Moritz
Mukherjee, Jean
Pönisch, Marion
Fiedler, Katja
Thess, Andreas
Mui, Barbara L
Hope, Michael J
Tam, Ying K
Horscroft, Nigel
Heidenreich, Regina
Fotin‐Mleczek, Mariola
Shoemaker, Charles B
Schlake, Thomas
author_sort Thran, Moritz
collection PubMed
description 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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spelling pubmed-56238552017-10-04 mRNA mediates passive vaccination against infectious agents, toxins, and tumors Thran, Moritz Mukherjee, Jean Pönisch, Marion Fiedler, Katja Thess, Andreas Mui, Barbara L Hope, Michael J Tam, Ying K Horscroft, Nigel Heidenreich, Regina Fotin‐Mleczek, Mariola Shoemaker, Charles B Schlake, Thomas EMBO Mol Med Research Articles 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. John Wiley and Sons Inc. 2017-08-09 2017-10 /pmc/articles/PMC5623855/ /pubmed/28794134 http://dx.doi.org/10.15252/emmm.201707678 Text en © 2017 CureVac AG. Published under the terms of the CC BY 4.0 license This is an open access article under the terms of the Creative Commons Attribution 4.0 (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Thran, Moritz
Mukherjee, Jean
Pönisch, Marion
Fiedler, Katja
Thess, Andreas
Mui, Barbara L
Hope, Michael J
Tam, Ying K
Horscroft, Nigel
Heidenreich, Regina
Fotin‐Mleczek, Mariola
Shoemaker, Charles B
Schlake, Thomas
mRNA mediates passive vaccination against infectious agents, toxins, and tumors
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 Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5623855/
https://www.ncbi.nlm.nih.gov/pubmed/28794134
http://dx.doi.org/10.15252/emmm.201707678
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