Viral Hemorrhagic Fevers in Pregnant Women and the Vaccine Landscape: Comparisons Between Yellow Fever, Ebola, and Lassa Fever

As research efforts have advanced to understand the pathophysiology of viral hemorrhagic fevers (VHF) and other epidemic viral infections and develop medical countermeasures such as vaccines, pregnant women have remained an underexamined subgroup. To better understand the implications of future outbreaks of VHF for pregnant women amidst an evolving vaccine landscape, we examine three pathogens—yellow fever, Ebola, and Lassa fever—each with different levels of evidence and understanding of disease in pregnancy and at varying stages of vaccine development. There are very limited data available on yellow fever disease in pregnancy and the current live-attenuated 17D yellow fever vaccine is recommended for pregnant women at high risk of exposure. Evidence on Ebola virus disease in pregnancy shows very high case fatality rates (CFRs) among pregnant women and their infants, with mixed evidence on whether mortality is higher in pregnant women than non-pregnant adults. The replication-competent rVSV-ZEBOV vaccine is currently being offered to at-risk pregnant women in the Democratic Republic of the Congo after a revision to an earlier protocol that excluded them. For Lassa fever, there is evidence that CFR is higher in pregnant individuals than non-pregnant adults, especially later in gestation, with high rates of fetal or perinatal loss associated with infection. There are currently no Lassa fever vaccine candidates that have been tested in humans. More evidence is needed to fully understand the implications of infection in pregnancy, but the existing data underscore the serious maternal and fetal health risks associated with each viral infection. It will also be critical to generate evidence on the safety profile of vaccine candidates as they advance through the pipeline to ensure timely and appropriate access for pregnant women at risk of infection. It is important that pregnant women be considered in the design and clinical trial phases of future vaccines.