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Maternally transferred mAbs protect neonatal mice from HSV-induced mortality and morbidity

Neonatal herpes simplex virus (nHSV) infections often result in significant mortality and neurological morbidity despite antiviral drug therapy. Maternally transferred herpes simplex virus (HSV)-specific antibodies reduce the risk of clinically overt nHSV, but this observation has not been translati...

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Autores principales: Backes, Iara M., Byrd, Brook K., Slein, Matthew D., Patel, Chaya D., Taylor, Sean A., Garland, Callaghan R., MacDonald, Scott W., Balazs, Alejandro B., Davis, Scott C., Ackerman, Margaret E., Leib, David A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9516843/
https://www.ncbi.nlm.nih.gov/pubmed/36156707
http://dx.doi.org/10.1084/jem.20220110
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author Backes, Iara M.
Byrd, Brook K.
Slein, Matthew D.
Patel, Chaya D.
Taylor, Sean A.
Garland, Callaghan R.
MacDonald, Scott W.
Balazs, Alejandro B.
Davis, Scott C.
Ackerman, Margaret E.
Leib, David A.
author_facet Backes, Iara M.
Byrd, Brook K.
Slein, Matthew D.
Patel, Chaya D.
Taylor, Sean A.
Garland, Callaghan R.
MacDonald, Scott W.
Balazs, Alejandro B.
Davis, Scott C.
Ackerman, Margaret E.
Leib, David A.
author_sort Backes, Iara M.
collection PubMed
description Neonatal herpes simplex virus (nHSV) infections often result in significant mortality and neurological morbidity despite antiviral drug therapy. Maternally transferred herpes simplex virus (HSV)-specific antibodies reduce the risk of clinically overt nHSV, but this observation has not been translationally applied. Using a neonatal mouse model, we tested the hypothesis that passive transfer of HSV-specific human mAbs can prevent mortality and morbidity associated with nHSV. The mAbs were expressed in vivo via vectored immunoprophylaxis or recombinantly. Through these maternally derived routes or through direct administration to pups, diverse mAbs to HSV glycoprotein D protected against neonatal HSV-1 and HSV-2 infection. Using in vivo bioluminescent imaging, both pre- and post-exposure mAb treatment significantly reduced viral load in mouse pups. Together these studies support the notion that HSV-specific mAb-based therapies could prevent or improve HSV infection outcomes in neonates.
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spelling pubmed-95168432023-03-26 Maternally transferred mAbs protect neonatal mice from HSV-induced mortality and morbidity Backes, Iara M. Byrd, Brook K. Slein, Matthew D. Patel, Chaya D. Taylor, Sean A. Garland, Callaghan R. MacDonald, Scott W. Balazs, Alejandro B. Davis, Scott C. Ackerman, Margaret E. Leib, David A. J Exp Med Article Neonatal herpes simplex virus (nHSV) infections often result in significant mortality and neurological morbidity despite antiviral drug therapy. Maternally transferred herpes simplex virus (HSV)-specific antibodies reduce the risk of clinically overt nHSV, but this observation has not been translationally applied. Using a neonatal mouse model, we tested the hypothesis that passive transfer of HSV-specific human mAbs can prevent mortality and morbidity associated with nHSV. The mAbs were expressed in vivo via vectored immunoprophylaxis or recombinantly. Through these maternally derived routes or through direct administration to pups, diverse mAbs to HSV glycoprotein D protected against neonatal HSV-1 and HSV-2 infection. Using in vivo bioluminescent imaging, both pre- and post-exposure mAb treatment significantly reduced viral load in mouse pups. Together these studies support the notion that HSV-specific mAb-based therapies could prevent or improve HSV infection outcomes in neonates. Rockefeller University Press 2022-09-26 /pmc/articles/PMC9516843/ /pubmed/36156707 http://dx.doi.org/10.1084/jem.20220110 Text en © 2022 Backes et al. https://creativecommons.org/licenses/by-nc-sa/4.0/http://www.rupress.org/terms/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Article
Backes, Iara M.
Byrd, Brook K.
Slein, Matthew D.
Patel, Chaya D.
Taylor, Sean A.
Garland, Callaghan R.
MacDonald, Scott W.
Balazs, Alejandro B.
Davis, Scott C.
Ackerman, Margaret E.
Leib, David A.
Maternally transferred mAbs protect neonatal mice from HSV-induced mortality and morbidity
title Maternally transferred mAbs protect neonatal mice from HSV-induced mortality and morbidity
title_full Maternally transferred mAbs protect neonatal mice from HSV-induced mortality and morbidity
title_fullStr Maternally transferred mAbs protect neonatal mice from HSV-induced mortality and morbidity
title_full_unstemmed Maternally transferred mAbs protect neonatal mice from HSV-induced mortality and morbidity
title_short Maternally transferred mAbs protect neonatal mice from HSV-induced mortality and morbidity
title_sort maternally transferred mabs protect neonatal mice from hsv-induced mortality and morbidity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9516843/
https://www.ncbi.nlm.nih.gov/pubmed/36156707
http://dx.doi.org/10.1084/jem.20220110
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