Uses of Human Monoclonal Antibodies to Human Cytomegalovirus and Varicella-Zoster Virus

Abstract

Herpesvirus infections are a major cause of morbidity and mortality in immunocompromised patients. Human cytomegalovirus (HCMV) is the causative agent in a wide spectrum of clinical diseases in these individuals (Weller, 1981). After organ or bone marrow transplantation, nearly all patients under certain conditions develop HCMV infections (Meyers, Fluornoy, and Thomas, 1986). Among allogeneic bone marrow transplant recipients, 15 to 20 percent will develop HCMV pneumonitis, with the mortality rate as high as 90 percent. Varicella-zoster virus (VZV), another member of the herpesvirus family, is also a significant pathogen for immunocompromised patients (Gershon, 1980; Straus, et al., 1988). For example, in children with leukemia or lymphoma, about 30 percent of those with varicella will develop pneumonitis, which is associated with a 7 percent mortality rate (Balfour, 1988). Although cell-mediated immunity is critical in recovery from HCMV and VZV infections, passive immunization with gammaglobulin has been shown both to prevent and to modify infection (Winston et al., 1982; Condie and O’Reilly, 1984; Paryani et al., 1984; Winston et al., 1987). Furthermore, high-dose gammaglobulin therapy in conjunction with administration of a new anti-viral agent, ganciclovir, has been shown effective in treating HCMV pneumonitis (Emanuel et al., 1988a; Reed et al., 1988; Schmidt et al., 1988). For these reasons, substantial efforts have been devoted to the production of human monoclonal antibodies (Humabs) to HCMV and VZV. Ultimately, these Humabs should replace human plasma as a source of antibodies in the prevention and treatment of HCMV and VZV infections.