title: Rat Cytomegalovirus Vaccine Prevents Accelerated Chronic Rejection in CMV-Naïve Recipients of Infected Donor Allograft Hearts.
abstract: Cytomegalovirus accelerates transplant vascular sclerosis (TVS) and chronic rejection (CR) in solid organ transplants; however, the mechanisms involved are unclear. We determined the efficacy of a CMV vaccine in preventing CMV-accelerated rat cardiac allograft rejection in naïve recipients of CMV+ donor hearts. F344 donor rats were infected with RCMV 5 days prior to heterotopic cardiac transplantation into CMV-naïve or H2 O2 -inactivated RCMV-vaccinated Lewis recipients. Recipients of RCMV-infected donor hearts rejected at POD59, whereas vaccinated recipients exhibited a significantly prolonged time to rejection-POD97, similar to recipients of uninfected donor hearts (POD108). Although all of the donor hearts were preinfected, the vaccinated recipients had lower graft and PBMC viral loads at POD 7 compared to unvaccinated controls. Adoptive T cell and passive antibody transfers from vaccinated Lewis rats into naïve recipients demonstrate that both T-cell and B-cell arms of the adaptive immune response provide protection against CMV-accelerated rejection. Similar findings were obtained when testing three different adjuvants in passive transfer experiments. We have determined that the timing of the vaccine prior to transplantation and the specific adjuvant play critical roles in mediating anti-viral responses and promoting graft survival. CMV vaccination prior to transplantation may effectively increase graft survival.
authors.affiliation: Department of Molecular Microbiology and Immunology, Oregon Health Sciences University, Portland, OR.|The Vaccine and Gene Therapy Institute, Oregon Health Sciences University, Beaverton, OR.
authors.forename: D N
authors.initials: DN
authors.lastname: Streblow
authors.affiliation: Department of Surgery, Oregon Health Sciences University, Portland, OR.
authors.forename: Y K
authors.initials: YK
authors.lastname: Hwee
authors.affiliation: The Vaccine and Gene Therapy Institute, Oregon Health Sciences University, Beaverton, OR.|Department of Surgery, Oregon Health Sciences University, Portland, OR.
authors.forename: C N
authors.initials: CN
authors.lastname: Kreklywich
authors.affiliation: Department of Surgery, Oregon Health Sciences University, Portland, OR.|Portland Veterans Affairs Medical Center, Portland, OR.
authors.forename: T
authors.initials: T
authors.lastname: Andoh
authors.affiliation: The Vaccine and Gene Therapy Institute, Oregon Health Sciences University, Beaverton, OR.
authors.forename: M
authors.initials: M
authors.lastname: Denton
authors.affiliation: The Vaccine and Gene Therapy Institute, Oregon Health Sciences University, Beaverton, OR.
authors.forename: P
authors.initials: P
authors.lastname: Smith
authors.affiliation: The Vaccine and Gene Therapy Institute, Oregon Health Sciences University, Beaverton, OR.
authors.forename: E
authors.initials: E
authors.lastname: Hart
authors.affiliation: The Vaccine and Gene Therapy Institute, Oregon Health Sciences University, Beaverton, OR.
authors.forename: R
authors.initials: R
authors.lastname: Broekel
authors.affiliation: The Vaccine and Gene Therapy Institute, Oregon Health Sciences University, Beaverton, OR.
authors.forename: C
authors.initials: C
authors.lastname: Pallett
authors.affiliation: The Vaccine and Gene Therapy Institute, Oregon Health Sciences University, Beaverton, OR.
authors.forename: K
authors.initials: K
authors.lastname: Rogers
authors.affiliation: The Vaccine and Gene Therapy Institute, Oregon Health Sciences University, Beaverton, OR.
authors.forename: A D
authors.initials: AD
authors.lastname: Streblow
authors.affiliation: The Vaccine and Gene Therapy Institute, Oregon Health Sciences University, Beaverton, OR.
authors.forename: M
authors.initials: M
authors.lastname: Chuop
authors.affiliation: Department of Molecular Microbiology and Immunology, Oregon Health Sciences University, Portland, OR.
authors.forename: A
authors.initials: A
authors.lastname: Perry
authors.affiliation: Department of Molecular Microbiology and Immunology, Oregon Health Sciences University, Portland, OR.|Division of Neuroscience, Oregon National Primate Research Center, Beaverton, OR.
authors.forename: M
authors.initials: M
authors.lastname: Slifka
authors.affiliation: Division of Biomedical Sciences, School of Medicine, University of California-Riverside, Riverside, CA.
authors.forename: I
authors.initials: I
authors.lastname: Messaoudi
authors.affiliation: Department of Molecular Microbiology and Immunology, Oregon Health Sciences University, Portland, OR.|Department of Surgery, Oregon Health Sciences University, Portland, OR.|Portland Veterans Affairs Medical Center, Portland, OR.
authors.forename: S L
authors.initials: SL
authors.lastname: Orloff
mesh_terms: D064591:Allografts; D000818:Animals; D015153:Blotting, Western; D003586:Cytomegalovirus Infections / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D022482:Cytomegalovirus Vaccines / Q000008:administration & dosage*; D004797:Enzyme-Linked Immunosorbent Assay; D006084:Graft Rejection / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D006085:Graft Survival / Q000276:immunology*; D016027:Heart Transplantation / Q000009:adverse effects*; D018146:Muromegalovirus / Q000276:immunology*; D016133:Polymerase Chain Reaction; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D014019:Tissue Donors; D066027:Transplant Recipients
chemical_list: D022482:Cytomegalovirus Vaccines
keywords: animal models; basic (laboratory) research / science; graft survival; heart transplantation / cardiology; infection and infectious agents; infectious disease; vaccine; viral: Cytomegalovirus (CMV)