Cytomegalovirus (CMV) infections remain a serious problem in hematopoietic stem cell transplant patients. Following transplantation CMV infections can cause peumonititis, hepatitis, enteritis, and marrow failure. CMV seropositive transplant recipients can be treated with antiviral agents such as ganciclovir at the onset of infection or at the time of stem cell engraphment, but ganciclovir therapy is associated with renal toxicity and suppression of neutrophil counts. Preliminary studies have found that adoptive immune therapy using CMV-reactive cytotoxic T lymphocytes (CTL) may be an effective and less toxic alternative to prevent CMV infection in seropositive recipients of marrow transplants. The purpose of this study is to develop new treatment strategies for producing CMV-reactive CTLs that can be used for adoptive immunetherapy and to better understand the cellular immune response to CMV. Current studies are focused on identifying the immune dominant peptides that can be used to stimulate CMV reactive CTLs. CMV contains over 200 proteins, but one protein, pp65, is the most immunogenic. Within pp65, CTLs from HLA-A*0201 people recognize only a single peptide, a nanomer pp65 495-503. We have found that for HLA-A*2401 people the immunodominant peptide is pp65 328-337. We are working to identify the immune dominant pp65 peptides for people with types HLA-A*0101 and HLA-A*0301. We have also begun collaborative studies with Dr. John Barrett, NHLBI. He is planning to vaccinate hematopoietic stem cell donors with a canary pox vector containing the gene for CMV proteins PP65 and IEP prior to the collection and transplantation of stem cells. We will be monitoring the donor's immune response to the vaccination.
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