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DMAb inoculation of synthetic cross reactive antibodies protects against lethal influenza A and B infections

Influenza virus remains a significant public health threat despite innovative vaccines and antiviral drugs. A major limitation to current vaccinations and therapies against influenza virus is pathogenic diversity generated by shift and drift. A simple, cost-effective passive immunization strategy vi...

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Autores principales: Elliott, Sarah T. C., Kallewaard, Nicole L., Benjamin, Ebony, Wachter-Rosati, Leslie, McAuliffe, Josephine M., Patel, Ami, Smith, Trevor R. F., Schultheis, Katherine, Park, Daniel H., Flingai, Seleeke, Wise, Megan C., Mendoza, Janess, Ramos, Stephanie, Broderick, Kate E., Yan, Jian, Humeau, Laurent M., Sardesai, Niranjan Y., Muthumani, Kar, Zhu, Qing, Weiner, David B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5627301/
https://www.ncbi.nlm.nih.gov/pubmed/29263874
http://dx.doi.org/10.1038/s41541-017-0020-x
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author Elliott, Sarah T. C.
Kallewaard, Nicole L.
Benjamin, Ebony
Wachter-Rosati, Leslie
McAuliffe, Josephine M.
Patel, Ami
Smith, Trevor R. F.
Schultheis, Katherine
Park, Daniel H.
Flingai, Seleeke
Wise, Megan C.
Mendoza, Janess
Ramos, Stephanie
Broderick, Kate E.
Yan, Jian
Humeau, Laurent M.
Sardesai, Niranjan Y.
Muthumani, Kar
Zhu, Qing
Weiner, David B.
author_facet Elliott, Sarah T. C.
Kallewaard, Nicole L.
Benjamin, Ebony
Wachter-Rosati, Leslie
McAuliffe, Josephine M.
Patel, Ami
Smith, Trevor R. F.
Schultheis, Katherine
Park, Daniel H.
Flingai, Seleeke
Wise, Megan C.
Mendoza, Janess
Ramos, Stephanie
Broderick, Kate E.
Yan, Jian
Humeau, Laurent M.
Sardesai, Niranjan Y.
Muthumani, Kar
Zhu, Qing
Weiner, David B.
author_sort Elliott, Sarah T. C.
collection PubMed
description Influenza virus remains a significant public health threat despite innovative vaccines and antiviral drugs. A major limitation to current vaccinations and therapies against influenza virus is pathogenic diversity generated by shift and drift. A simple, cost-effective passive immunization strategy via in vivo production of cross-protective antibody molecules may augment existing vaccines and antiviral drugs in seasonal and pandemic outbreaks. We engineered synthetic plasmid DNA to encode two novel and broadly cross-protective monoclonal antibodies targeting influenza A and B. We utilized enhanced in vivo delivery of these plasmid DNA-encoded monoclonal antibody (DMAb) constructs and show that this strategy induces robust levels of functional antibodies directed against influenza A and B viruses in mouse sera. Mice receiving a single inoculation with anti-influenza A DMAb survive lethal Group 1 H1 and Group 2 H3 influenza A challenges, while inoculation with anti-influenza B DMAb yields protection against lethal Victoria and Yamagata lineage influenza B morbidity and mortality. Furthermore, these two DMAbs can be delivered coordinately resulting in exceptionally broad protection against both influenza A and B. We demonstrate this protection is similar to that achieved by conventional protein antibody delivery. DMAbs warrant further investigation as a novel immune therapy platform with distinct advantages for sustained immunoprophylaxis against influenza.
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spelling pubmed-56273012017-12-20 DMAb inoculation of synthetic cross reactive antibodies protects against lethal influenza A and B infections Elliott, Sarah T. C. Kallewaard, Nicole L. Benjamin, Ebony Wachter-Rosati, Leslie McAuliffe, Josephine M. Patel, Ami Smith, Trevor R. F. Schultheis, Katherine Park, Daniel H. Flingai, Seleeke Wise, Megan C. Mendoza, Janess Ramos, Stephanie Broderick, Kate E. Yan, Jian Humeau, Laurent M. Sardesai, Niranjan Y. Muthumani, Kar Zhu, Qing Weiner, David B. NPJ Vaccines Article Influenza virus remains a significant public health threat despite innovative vaccines and antiviral drugs. A major limitation to current vaccinations and therapies against influenza virus is pathogenic diversity generated by shift and drift. A simple, cost-effective passive immunization strategy via in vivo production of cross-protective antibody molecules may augment existing vaccines and antiviral drugs in seasonal and pandemic outbreaks. We engineered synthetic plasmid DNA to encode two novel and broadly cross-protective monoclonal antibodies targeting influenza A and B. We utilized enhanced in vivo delivery of these plasmid DNA-encoded monoclonal antibody (DMAb) constructs and show that this strategy induces robust levels of functional antibodies directed against influenza A and B viruses in mouse sera. Mice receiving a single inoculation with anti-influenza A DMAb survive lethal Group 1 H1 and Group 2 H3 influenza A challenges, while inoculation with anti-influenza B DMAb yields protection against lethal Victoria and Yamagata lineage influenza B morbidity and mortality. Furthermore, these two DMAbs can be delivered coordinately resulting in exceptionally broad protection against both influenza A and B. We demonstrate this protection is similar to that achieved by conventional protein antibody delivery. DMAbs warrant further investigation as a novel immune therapy platform with distinct advantages for sustained immunoprophylaxis against influenza. Nature Publishing Group UK 2017-07-06 /pmc/articles/PMC5627301/ /pubmed/29263874 http://dx.doi.org/10.1038/s41541-017-0020-x Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Elliott, Sarah T. C.
Kallewaard, Nicole L.
Benjamin, Ebony
Wachter-Rosati, Leslie
McAuliffe, Josephine M.
Patel, Ami
Smith, Trevor R. F.
Schultheis, Katherine
Park, Daniel H.
Flingai, Seleeke
Wise, Megan C.
Mendoza, Janess
Ramos, Stephanie
Broderick, Kate E.
Yan, Jian
Humeau, Laurent M.
Sardesai, Niranjan Y.
Muthumani, Kar
Zhu, Qing
Weiner, David B.
DMAb inoculation of synthetic cross reactive antibodies protects against lethal influenza A and B infections
title DMAb inoculation of synthetic cross reactive antibodies protects against lethal influenza A and B infections
title_full DMAb inoculation of synthetic cross reactive antibodies protects against lethal influenza A and B infections
title_fullStr DMAb inoculation of synthetic cross reactive antibodies protects against lethal influenza A and B infections
title_full_unstemmed DMAb inoculation of synthetic cross reactive antibodies protects against lethal influenza A and B infections
title_short DMAb inoculation of synthetic cross reactive antibodies protects against lethal influenza A and B infections
title_sort dmab inoculation of synthetic cross reactive antibodies protects against lethal influenza a and b infections
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5627301/
https://www.ncbi.nlm.nih.gov/pubmed/29263874
http://dx.doi.org/10.1038/s41541-017-0020-x
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