Active Areas of Research
1. Guinea Pig Model of Congenital Infection
The Schleiss laboratory has been engaged in the study of protection against congenital and perinatal CMV infection since the late 1980s, when Dr. Schleiss began basic science studies of CMV transcription and gene regulation at the Fred Hutchinson Cancer Research Center in Seattle, Washington. Since cytomegaloviruses are species-specific, the human CMV virus cannot be used in small animal research models. Thus, studies of interventions designed to ensure optimal pregnancy outcomes must employ the use of species-specific strains of CMV. One such strain of CMV, unique to guinea pigs, is the guinea pig cytomegalovirus (GPCMV), and this virus provides a compelling model to study congenital transmission, since the guinea pig placenta is very similar to the human placenta. Moreover, in the GPCMV model, the virus readily crosses the placenta, infecting the unborn pup. This feature is unique to guinea pigs, and is not seen in rats or mice - making this the preferred small animal model of transplacental CMV infection and pathogenesis. The laboratory uses this model to study: 1) the impact of specific viral genes and gene products on injury and pathogenesis in the pup; 2) the ability of antiviral drugs to prevent transmission of virus and/or development of disease; 3) immunological markers of protection that can be applied to congenital CMV infection in people.
2. Vaccines against Congenital Infection
Using the GPCMV model, the Schleiss laboratory has pursued two general strategies that aim to define what would be required for a CMV vaccine in women. The first general approach is to generate live, attenuated vaccines based on targeted deletion of viral immune evasion genes encoded by the CMV virus. Such viruses could combine the attributes of improved immune response and better safety profile. The second general approach is that of a subunit vaccine based on virally encoded protein(s) important in the immune response to infection. General categories of CMV subunit vaccines include adjuvanted recombinant protein vaccines based on recombinant forms of the glycoprotein B (gB) protein; vaccines based on gB alone, or in combination with a tegument protein, UL83 (also know as pp65) and, in some cases, the major immediate early protein 1 (IE1) generated using viral or nucleic acid-based vectors; vaccines based on generation of virus-like particles (VLP) expressing combinations of these CMV gene products; and peptide-based vaccines based on T-cell epitopes (usually from UL83) important in protection against CMV disease. All of these approaches are under study in the laboratory.