Cytomegalovirus (CMV) Evolution to evade vaccine-elicited antibody responses
The CDC estimates that a child is born every hour in the United States with permanent neurologic disability resulting from congenital cytomegalovirus (CMV) infection. Indeed, CMV is the most common cause of infection in newborn infants worldwide, causing deafness and neurologic disease in afflicted children. CMV infection is passed from mother to infant in the womb. Our laboratory is working to develop a vaccine to stop women from becoming infected with CMV while pregnant, and thus to prevent them from subsequently passing that infection on to their unborn child. Previous CMV vaccines have demonstrated only modest success in clinical trials. We suggest that vaccine failure occurs because of CMV evolution in response to the immune response mounted against the virus in vaccinated individuals. Therefore, in the this project, we will attempt to identify changes in the viral structure that occur following vaccination. These changes indicate locations of viral mutation, which allow the virus to evade the host immune system. Identification of these locations of virus evolution will enable the rational design of a vaccine such that the virus is not able to mutate to avoid the vaccine-induced immune response.
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Nelson CS, Vera Cruz D, Su M, et al. (2019). Intrahost dynamics of human cytomegalovirus variants acquired by seronegative glycoprotein B vaccinees. Journal of Virology 93(5).