Grant: Project Grant

Congenital cytomegalovirus (CMV) infection causes birth defects in >2 per 1,000 births worldwide. As such, a vaccine to prevent CMV infection is needed. Most people in the world acquire CMV during early childhood from CMV in breast milk, saliva or urine. Children are often infected with CMV by their mothers, but mothers are frequently also infected by children, and interrupting the cycle of transmission between mothers and children is the key to reducing the enormous global health burden from CMV. Our study will guide the development of a CMV vaccine by characterizing the specific viral variants and modes of transmission between mothers and children. We have shown that only one or very few individual viruses that are able to successfully establish infection, which we call transmitted/founder (T/F) viruses. We are able to capture CMV transmission events between mothers and children, and determine the precise time of infection. Because CMV is highly genetically variable, we can use next-generation sequencing (NGS) to distinguish viruses from different individuals, as well as between compartments (e.g., breast milk, saliva, or urine) in the same individual. Thus, we are able to determine the exact source of a CMV infection. We can also measure the number of viruses present, and sequence of the entire genome of T/F viruses that initiate CMV infection. We will enroll a prospective cohort of 100 pregnant Kenyan women and their children, and collect samples of breast milk, saliva, urine, and blood to measure CMV viral loads and sequence the T/F viruses that infect infants and mothers. Our project will be conducted in Nairobi, Kenya, where our team has worked for >20 years on maternal-child viral infections, and brings together experts in epidemiology, virology, genomics, and mathematical modeling. This work will be invaluable for defining optimal CMV vaccine targets and evaluating vaccine strategies to prevent the transmission and morbidity of CMV.