Sonia GazeauCatherine ByrneDaniel CoombsColin KunzweilerRenato Calabro CalheirosJohn Diaz-DecaroSoren GanttMorgan CraigNakhchivan State University2026-06-172026-06-172026-08-21https://doi.org/10.1016/j.vaccine.2026.128788https://rims.khazar.org/handle/123456789/1378Background: Congenital cytomegalovirus infection (cCMVi) is a major global health problem and a leading cause of childhood hearing, visual, and intellectual disability. Development of an effective vaccine against CMV is a high priority, and there is optimism that one will be achieved soon. Previous mathematical modelling to predict the impact of CMV vaccination in low CMV seroprevalence, high-income populations indicate that vaccinating infants could be a highly efficient strategy to prevent cCMVi, even with only a modestly effective vaccine (i.e., <50% protective against primary infection). However, whether vaccinating infants is optimal in high CMV seroprevalence settings, where rates of cCMVi are correspondingly higher, is unclear. Methods: We adjusted our existing agent-based stochastic model to study CMV vaccine efficacy in high seroprevalence settings (reaching 90%) with Brazil as a test case. Results: Our results suggest that vaccinating 12-year-old girls and women of childbearing age would have limited ability to reduce cCMVi rates in Brazil, even with a vaccine conferring complete life-long protection against CMV infection. In contrast, vaccinating infants was predicted to provide substantial long-term reductions in the number of cCMVi cases in Brazil, even if it only induced protection equivalent to natural immunity against CMV reinfection and reactivation. Further, our model predicted that if two-thirds of Brazilian infants were vaccinated, a modestly effective vaccine would reduce the number of cCMVi cases by up to 76%. Conclusion: Together with results from other studies, this analysis underscores that infancy is likely the optimal target age for CMV vaccination to prevent cCMVi in all populations, regardless of the CMV seroprevalence. Furthermore, our findings predict large reductions in disease due to cCMVi worldwide through attainable vaccination scenarios.en-USCytomegalovirus CMV Vaccination Mathematical modellingjournal-article