title: Induction of cytomegalovirus-specific T cell responses in healthy volunteers and allogeneic stem cell recipients using vaccination with messenger RNA-transfected dendritic cells.
abstract: BACKGROUND
  Infection with human cytomegalovirus (CMV) is a significant cause of morbidity and mortality in solid organ and hematopoietic stem cell transplant (HSCT) recipients.
  
  
  METHODS
  The present study explored the safety, feasibility, and immunogenicity of CMV pp65 messenger RNA-loaded autologous monocyte-derived dendritic cells (DC) as a cellular vaccine for active immunization in healthy volunteers and allogeneic HSCT recipients. Four CMV-seronegative healthy volunteers and three allogeneic HSCT recipients were included in the study. Four clinical-grade autologous monocyte-derived DC vaccines were prepared after a single leukapheresis procedure and administered intradermally at a weekly interval.
  
  
  RESULTS
  De novo induction of CMV-specific T-cell responses was detected in three of four healthy volunteers without serious adverse events. Of the HSCT recipients, none developed CMV disease and one of two patients displayed a remarkable threefold increase in CMV pp65-specific T cells on completion of the DC vaccination trial.
  
  
  CONCLUSIONS
  In conclusion, our DC vaccination strategy induced or expanded a CMV-specific cellular response in four of six efficacy-evaluable study subjects, providing a base for its further exploration in larger cohorts.
authors: 1 Department of Nephrology-Hypertension, Antwerp University Hospital, Edegem, Belgium. 2 Laboratory of Experimental Medicine and Pediatrics, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium. 3 Laboratory of Experimental Hematology, Vaccine and Infectious Disease Institute (Vaxinfectio), Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium. 4 Center for Cell Therapy and Regenerative Medicine, Antwerp University Hospital, Edegem, Belgium. 5 Department of Hematology, Antwerp University Hospital, Edegem, Belgium. 6 Centre for the Evaluation of Vaccination (CEV), Vaccine & Infectious Disease Institute (Vaxinfectio), Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium. 7 Department of Microbiology, Antwerp University Hospital, Edegem, Belgium.
authors: Amaryllis H
authors: AH
authors: Van Craenenbroeck
authors: Evelien L J
authors: EL
authors: Smits
authors: Sébastien
authors: S
authors: Anguille
authors: Ann
authors: A
authors: Van de Velde
authors: Barbara
authors: B
authors: Stein
authors: Tessa
authors: T
authors: Braeckman
authors: Kirsten
authors: K
authors: Van Camp
authors: Griet
authors: G
authors: Nijs
authors: Margareta
authors: M
authors: Ieven
authors: Herman
authors: H
authors: Goossens
authors: Zwi N
authors: ZN
authors: Berneman
authors: Viggo F I
authors: VF
authors: Van Tendeloo
authors: Gert A
authors: GA
authors: Verpooten
authors: Pierre
authors: P
authors: Van Damme
authors: Nathalie
authors: N
authors: Cools
mesh_terms: D000328:Adult; D001530:Belgium; D003587:Cytomegalovirus / Q000235:genetics / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D022482:Cytomegalovirus Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000235:genetics / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000637:transplantation* / Q000821:virology; D005240:Feasibility Studies; D005260:Female; D064368:Healthy Volunteers; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007115:Immunization Schedule; D007271:Injections, Intradermal; D008297:Male; D008875:Middle Aged; D010750:Phosphoproteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D012367:RNA, Viral / Q000096:biosynthesis* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology; D013997:Time Factors; D014162:Transfection; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014611:Vaccination; D014763:Viral Matrix Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D055815:Young Adult
chemical_list: D022482:Cytomegalovirus Vaccines; D010750:Phosphoproteins; D012333:RNA, Messenger; D012367:RNA, Viral; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa