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 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.

HSP90 is part of a protein complex with the L polymerase of Rift Valley fever phlebovirus and prevents its degradation by the proteasome during the viral genome replication/transcription stage

“…These studies highlight the potential of HSP90 inhibitors for development of therapeutics against RVFV infection and warrant in vivo efficacy studies of these inhibitors against RVFV infection in future studies. Such potentially effective host-based approaches could complement recent promising advances, such as demonstration of potent neutralizing activity of a human antibody that prevents vertical RVFV transmission in a rat model (McMillen et al, 2023). In this regard, 17-AAG is a well-studied HSP90 inhibitor that is well tolerated at biologically active doses and has progressed to phase III clinical trials (Magwenyane et al, 2022).…”