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

Cynthia M. McMillen, Nathaniel S. Chapman, Ryan M. Hoehl, Lauren B. Skvarca, Madeline M. Schwarz, Laura S. Handal, James E. Crowe () and Amy L. Hartman ()
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Cynthia M. McMillen: University of Pittsburgh, Center for Vaccine Research
Nathaniel S. Chapman: Vanderbilt University Medical Center, Department of Pathology, Microbiology and Immunology
Ryan M. Hoehl: University of Pittsburgh, Center for Vaccine Research
Lauren B. Skvarca: University of Pittsburgh Medical Center, Magee-Womens Hospital, Department of Pathology
Madeline M. Schwarz: University of Pittsburgh, Center for Vaccine Research
Laura S. Handal: Vanderbilt University Medical Center, Vanderbilt Vaccine Center
James E. Crowe: Vanderbilt University Medical Center, Department of Pathology, Microbiology and Immunology
Amy L. Hartman: University of Pittsburgh, Center for Vaccine Research

Nature Communications, 2023, vol. 14, issue 1, 1-14

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-40187-z

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