Multiple lines of evidence indicate that in the transplant population humancytomegalovirus (HCMV) infection and its associated diseases are controlled by humoraland cellular immune responses similar to those that arise in asymptomatic, healthyindividuals during a naturally-acquired infection. The dominant antibody response toHCMV is to the major surface glycoprotein B (gB) and the dominant cellular immuneresponse is to the tegument phosphoprotein (pp65). We propose that animmunotherapeutic plasmid DNA (pDNA) vaccination approach that induces therequisite responses to major immunological targets of HCMV may provide relief fromHCMV-associated diseases in the transplant setting. We have developed gene-basedimmunotherapeutic products consisting of pDNAs encoding gB and pp65 of HCMV.When tested individually in mice, both pDNAs were highly immunogenic. Relative tovaccination with either gB or pp65 pDNA delivered alone, vaccination with gB and pp65pDNAs delivered together in phosphate-buffered saline (PBS) elicited reduced antibodyand T cell responses to each antigen. Formulating this bivalent vaccine with apoloxamer-based delivery system (VF-P1205-02A), however, significantly increased theantigen-specific immune responses relative to those induced with the bivalent vaccine inPBS, and completely abrogated the decrease in pp65-specific T cell responses observedin mice co-vaccinated with the pDNAs in PBS. Based on these data, and a favorablesafety and toxicity profile in pre-clinical studies, the bivalent HCMV vaccine consistingof gB and pp65 pDNAs delivered with VF-P1205-02A has advanced to human clinicaltrials.