Cargando…
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...
Autores principales: | , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1783268163030351872 |
---|---|
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. |
format | Online Article Text |
id | pubmed-5623855 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT thranmoritz mrnamediatespassivevaccinationagainstinfectiousagentstoxinsandtumors AT mukherjeejean mrnamediatespassivevaccinationagainstinfectiousagentstoxinsandtumors AT ponischmarion mrnamediatespassivevaccinationagainstinfectiousagentstoxinsandtumors AT fiedlerkatja mrnamediatespassivevaccinationagainstinfectiousagentstoxinsandtumors AT thessandreas mrnamediatespassivevaccinationagainstinfectiousagentstoxinsandtumors AT muibarbaral mrnamediatespassivevaccinationagainstinfectiousagentstoxinsandtumors AT hopemichaelj mrnamediatespassivevaccinationagainstinfectiousagentstoxinsandtumors AT tamyingk mrnamediatespassivevaccinationagainstinfectiousagentstoxinsandtumors AT horscroftnigel mrnamediatespassivevaccinationagainstinfectiousagentstoxinsandtumors AT heidenreichregina mrnamediatespassivevaccinationagainstinfectiousagentstoxinsandtumors AT fotinmleczekmariola mrnamediatespassivevaccinationagainstinfectiousagentstoxinsandtumors AT shoemakercharlesb mrnamediatespassivevaccinationagainstinfectiousagentstoxinsandtumors AT schlakethomas mrnamediatespassivevaccinationagainstinfectiousagentstoxinsandtumors |