PHASE II/II TRIAL OF RECOMBINANT CMV GB VACCINE IN POSTPARTUM WOMEN

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Project 1 will contribute to the overall goal of the Program by evaluating a strategy for measuring efficacy of a vaccine for prevention of congenital CMV infection. Although congenital cytomegalovirus (CMV) infection is the leading infectious cause of brain disease and the leading cause of sensorineural hearing loss in children, an effective means of preventing maternal and congenital infection is not available. Vaccines have been developed, but none has been evaluated for efficacy to prevent congenital CMV infection. The major obstacle to overcome in developing vaccines to prevent congenital CMV infection is uncertainty over how to conduct an efficacy trial. A trial aimed at preventing congenital CMV infection would require enrollment and immunization of large numbers of seronegative pregnant women prior to pregnancy, following a sufficient number of them through a subsequent pregnancy and screening newborns for congenital CMV infection. Because of the uncertainty over when the subsequent pregnancy will occur, the costly follow-up of vaccines, the need to screen newborns for CMV infection and the lack of knowledge of the rate of maternal and congenital infection in most populations, such a trial is probably too expensive and risky for any vaccine manufacturer to undertake without resolving some of the uncertainties. This proposal will demonstrate an efficient means of evaluating the efficacy of a CMV vaccine, targeting postpartum women from a population with a demonstrated high rate of maternal and congenital CMV infection between pregnancies. Women on postpartum wards of two hospitals in the UAB Medical Center will be screened for antibody to CMV; 400 seronegative women will be enrolled over two years in the vaccine trial. Participants will be randomized to receive Chiron CMV gB vaccine or placebo on a 0,1,6 month schedule and followed for CMV infection for a minimum of three years after enrollment. A serologic assay for antibody to CMV tegument proteins pp50, pp65 and pp150 will be used to screen vaccines for CMV infection. Four previous work in this population, over 65% of participants are expected to complete a pregnancy during the course of the study; all newborns will be screened for congenital CMV infection. This study will define the safety and immunogenicity of this CMV gB vaccine in postpartum women. In addition, it will allow assessment of the durability of the vaccine induced immune response (antibody to gB, neutralizing antibody and CD4 proliferation), and the relationship between level of immune response and efficacy for prevention of maternal infection. It will also define congenital infection rate in the study population, providing the data needed to calculate sample size for a trial that will test efficacy of a vaccine for prevention of congenital CMV infection. This trial will provide samples for detailed comparison of vaccine induced immunity with immunity from naturally acquired infection, and detailed analysis of the impact of vaccine induced immunity on the virologic and immunologic response to infection that are the focus of Project 2.