Annually, intrauterine infection with CMV causes up to 8,000 infants to be mentally retarded an/or deaf. Seronegative mothers with children under age 3 years attending day care and the seronegative women caring for these children have rates of infection between 10% and 40% per year, compared to a rate of less than 5% among other women. The majority of these women are planning additional children and this may have an increase in the incidence of primary maternal infection during pregnancy. The earlier studies found that among women of childbearing age immunity induced by a primary infection protects against secondary infection but a weak neutralizing antibody (NT) response to a live attenuated CMV vaccine (Towne) did not. The earlier studies have also found a linear correlation between serum NT and the levels of mucosal IgG to CMV glycoprotein gB. These observations support the suggestion that neutralizing antibodies against CMV protect mothers from acquiring CMV infections from their children, by creating an immune barrier, comprised of neutralizing IgG molecules at the mucosal surfaces of the upper respiratory tract. To test this hypothesis the plan is to evaluate a dose of CMV vaccine that produces NT equal to those induced by wild-type virus. Seronegative women (all with children under age 3 years shedding CMV) will be randomized into vaccinees and controls (hepatitis vaccine) using a double blinded protocol. Vaccine and controls will be matched for maternal and children's age, race, marital status, and socioeconomic status. Each women and her family members will be monitored for 3 years. The prevalent strains of CMV shed by the children attending each day care center will be determined. Vaccine efficacy will be assessed by comparing the incidence of CMV acquisition in vaccinees and controls and associated with the following parameters of the immune responses: IgG, IgG to CMV gB, neutralizing titers, IgG responses characterized by subclass and immunoblotting, Lymphoproliferative responses (CD4 plus Th), and mucosal immunity. Children born to vaccinees will be monitored for CMV infections for 2 years. This vaccine trial will determine if immunization against reinfection with an exogenous strain of CMV is possible.
