(based on the investigator s abstract): The outcome of CMV reactivation in late stage AIDS is unpredictable. Cellular immunity to CMV is profoundly suppressed but some humoral immunity is retained. Humoral immunity is induced in large part by the envelope glycoproteins of CMV which include the UL55 (gB), UL75-UL100 (gH-gL) and the UL100. The studies of humoral immunity, as well as the focus of immunotherapy, has been immunity to gB. However, immunotherapy with gB based regimens has not been encouraging in severely immunosuppresed HIV-infected patients. The gH glycoproteins of most herpes viruses have been recently recognized to require association with gL for optimum antigenicity. Immunity to neither the Gh-GL complex nor the components has been studied in HIV-infected subjects. Because immunotherapy by vaccine or passive antibody transfer is a needed adjunct to CMV antiviral therapy, the study of the immunology of the gH-gL complex has special significance for CMV antiviral therapy. This study examines the immunogenicity of gH, gL, and the gH-gL complex in both animal models and humans undergoing natural CMV infection. All configurations of the gH-gL complex will be studied using immunization to compare antigenicity in guinea pigs and the use of monoclonal antibodies to define the regions of the glycoproteins associated with biological activities such as neutralization, inhibition of penetration, and cell-to-cell spread. The humoral immune response to the gH-gL complex and its individual components will be studied in sera from HIV-infected patients to determine whether the gH-gL complex is required for protective immunity. The correlate of protection will be temporal association with reduction of viremia as quantified by DNA amplification methods, in a cohort of patients who have been prospectively monitored for over two years.
| Rasmussen, Lucy; Geissler, Aimee; Winters, Mark (2003) Inter- and intragenic variations complicate the molecular epidemiology of human cytomegalovirus. J Infect Dis 187:809-19 |
| Rasmussen, Lucy; Cowan, Catherine M (2003) Neutralizing antibody to gB2 human cytomegalovirus does not prevent reactivation in patients with human immunodeficiency virus infection. J Gen Virol 84:1853-7 |
| Rasmussen, Lucy; Geissler, Aimee; Cowan, Catherine et al. (2002) The genes encoding the gCIII complex of human cytomegalovirus exist in highly diverse combinations in clinical isolates. J Virol 76:10841-8 |
