Vertical transmission, pregnancy outcomes and treatment of Mpox virus infection in a translational pregnant macaque model

PROJECT SUMMARY/ABSTRACT Mpox (formerly monkeypox) virus (MPXV) is a serious global health concern that recently caused a significant outbreak in the United States, resulting in over 30,000 infections. MPXV infections are known to cause high rates of fetal demise, particularly with clade I MPXV which is endemic in Central Africa. It is unclear whether clade IIb MPXV, which circulated worldwide and within the United States, also causes adverse pregnancy outcomes because the outbreak is so recent. Defining the rate of adverse pregnancy outcomes and whether vertical transmission occurs with clade IIb MPXV is a critical public global health challenge. In addition, it is uncertain whether the antiviral drug tecovirimat, currently used off label to treat mpox disease, can improve pregnancy outcomes when administered early in the course of infection during pregnancy. Determining whether early treatment with tecovirimat improves pregnancy outcomes is essential for informing clinical management. We developed a preclinical rhesus macaque model of prenatal Zika virus infection, defined vertical transmission pathways, and assessed adverse pregnancy outcomes. We will adapt this expertise to develop a preclinical rhesus macaque model of mpox disease in pregnancy. We hypothesize that MPXV will be vertically transmitted with inoculation in early gestation, that there will be an increase in adverse pregnancy outcomes with maternal infection, and that the antiviral drug tecovirimat will decrease maternal disease and improve pregnancy outcomes. We propose the following aims to test these hypotheses. Aim 1: To define the rate and pathways of vertical transmission following MPXV infection in early pregnancy. Aim 2: To define the association between maternal mpox disease severity and pregnancy outcomes following MPXV infection in early pregnancy. Aim 3: To determine if early antiviral treatment improves maternal mpox disease and pregnancy outcomes. Accomplishing these aims will fill a significant knowledge gap in our clinical management of pregnant persons infected with MPXV: whether infection results in a higher rate of adverse pregnancy outcomes, whether vertical transmission occurs, and whether early administration of tecovirimat improves maternal mpox disease and pregnancy outcomes. Given the limited clinical trial data on mpox in pregnant women, the findings from this study will be pivotal in informing future clinical trials and improving the clinical management of pregnant women with MPXV infection, leading to better health outcomes for both mothers and infants.