A highly potent human neutralizing antibody prevents vertical transmission of Rift Valley fever virus in a rat model

Abstract Rift Valley fever virus (RVFV) is an emerging mosquito-transmitted virus that circulates in livestock and humans in Africa and the Middle East. Outbreaks lead to high rates of miscarriages in domesticated livestock. Women are also at risk of vertical virus transmission and late-term miscarr...

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Main Authors: Cynthia M. McMillen, Nathaniel S. Chapman, Ryan M. Hoehl, Lauren B. Skvarca, Madeline M. Schwarz, Laura S. Handal, James E. Crowe, Amy L. Hartman
Format: Article
Language:English
Published: Nature Portfolio 2023-07-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-023-40187-z
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author Cynthia M. McMillen
Nathaniel S. Chapman
Ryan M. Hoehl
Lauren B. Skvarca
Madeline M. Schwarz
Laura S. Handal
James E. Crowe
Amy L. Hartman
author_facet Cynthia M. McMillen
Nathaniel S. Chapman
Ryan M. Hoehl
Lauren B. Skvarca
Madeline M. Schwarz
Laura S. Handal
James E. Crowe
Amy L. Hartman
author_sort Cynthia M. McMillen
collection DOAJ
description Abstract Rift Valley fever virus (RVFV) is an emerging mosquito-transmitted virus that circulates in livestock and humans in Africa and the Middle East. Outbreaks lead to high rates of miscarriages in domesticated livestock. Women are also at risk of vertical virus transmission and late-term miscarriages. MAb RVFV-268 is a highly potent recombinant neutralizing human monoclonal antibody that targets RVFV. Here we show that mAb RVFV-268 reduces viral replication in rat placenta explant cultures and prevents vertical transmission in a rat model of congenital RVF. Passive transfer of mAb RVFV-268 from mother to fetus occurs as early as 6 h after administration and persists through 24 h. Administering mAb RVFV-268 2 h prior to RVFV challenge or 24 h post-challenge protects the dams and offspring from RVFV infection. These findings support mAb RVFV-268 as a pre- and post-infection treatment to subvert RVFV infection and vertical transmission, thus protecting the mother and offspring.
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spelling doaj.art-b005e172a9a3481db7bdb83e145d536f2023-07-30T11:19:27ZengNature PortfolioNature Communications2041-17232023-07-0114111410.1038/s41467-023-40187-zA highly potent human neutralizing antibody prevents vertical transmission of Rift Valley fever virus in a rat modelCynthia M. McMillen0Nathaniel S. Chapman1Ryan M. Hoehl2Lauren B. Skvarca3Madeline M. Schwarz4Laura S. Handal5James E. Crowe6Amy L. Hartman7University of Pittsburgh, Center for Vaccine ResearchVanderbilt University Medical Center, Department of Pathology, Microbiology and ImmunologyUniversity of Pittsburgh, Center for Vaccine ResearchUniversity of Pittsburgh Medical Center, Magee-Womens Hospital, Department of PathologyUniversity of Pittsburgh, Center for Vaccine ResearchVanderbilt University Medical Center, Vanderbilt Vaccine CenterVanderbilt University Medical Center, Department of Pathology, Microbiology and ImmunologyUniversity of Pittsburgh, Center for Vaccine ResearchAbstract Rift Valley fever virus (RVFV) is an emerging mosquito-transmitted virus that circulates in livestock and humans in Africa and the Middle East. Outbreaks lead to high rates of miscarriages in domesticated livestock. Women are also at risk of vertical virus transmission and late-term miscarriages. MAb RVFV-268 is a highly potent recombinant neutralizing human monoclonal antibody that targets RVFV. Here we show that mAb RVFV-268 reduces viral replication in rat placenta explant cultures and prevents vertical transmission in a rat model of congenital RVF. Passive transfer of mAb RVFV-268 from mother to fetus occurs as early as 6 h after administration and persists through 24 h. Administering mAb RVFV-268 2 h prior to RVFV challenge or 24 h post-challenge protects the dams and offspring from RVFV infection. These findings support mAb RVFV-268 as a pre- and post-infection treatment to subvert RVFV infection and vertical transmission, thus protecting the mother and offspring.https://doi.org/10.1038/s41467-023-40187-z
spellingShingle Cynthia M. McMillen
Nathaniel S. Chapman
Ryan M. Hoehl
Lauren B. Skvarca
Madeline M. Schwarz
Laura S. Handal
James E. Crowe
Amy L. Hartman
A highly potent human neutralizing antibody prevents vertical transmission of Rift Valley fever virus in a rat model
Nature Communications
title A highly potent human neutralizing antibody prevents vertical transmission of Rift Valley fever virus in a rat model
title_full A highly potent human neutralizing antibody prevents vertical transmission of Rift Valley fever virus in a rat model
title_fullStr A highly potent human neutralizing antibody prevents vertical transmission of Rift Valley fever virus in a rat model
title_full_unstemmed A highly potent human neutralizing antibody prevents vertical transmission of Rift Valley fever virus in a rat model
title_short A highly potent human neutralizing antibody prevents vertical transmission of Rift Valley fever virus in a rat model
title_sort highly potent human neutralizing antibody prevents vertical transmission of rift valley fever virus in a rat model
url https://doi.org/10.1038/s41467-023-40187-z
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