Induction of cytomegalovirus-specific T cell responses in healthy volunteers and allogeneic stem cell recipients using vaccination with messenger RNA-transfected dendritic cells

Amaryllis H Van Craenenbroeck, Evelien L J Smits, Sébastien Anguille, Ann Van de Velde, Barbara Stein, Tessa Braeckman, Kirsten Van Camp, Griet Nijs, Margareta Ieven, Herman Goossens, Zwi N Berneman, Viggo F I Van Tendeloo, Gert A Verpooten, Pierre Van Damme, Nathalie Cools

Research output: Contribution to journalArticle

20 Citations (Scopus)

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.

CONCLUSION: 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.

Original languageEnglish
Pages (from-to)120-127
Number of pages8
JournalTransplantation
Volume99
Issue number1
DOIs
Publication statusPublished - Jan 2015

Keywords

  • Adult
  • Belgium
  • Cytomegalovirus/genetics
  • Cytomegalovirus Infections/immunology
  • Cytomegalovirus Vaccines/administration & dosage
  • Dendritic Cells/immunology
  • Feasibility Studies
  • Female
  • Healthy Volunteers
  • Hematopoietic Stem Cell Transplantation/adverse effects
  • Humans
  • Immunization Schedule
  • Injections, Intradermal
  • Male
  • Middle Aged
  • Phosphoproteins/biosynthesis
  • RNA, Messenger/biosynthesis
  • RNA, Viral/biosynthesis
  • T-Lymphocytes/immunology
  • Time Factors
  • Transfection
  • Transplantation, Homologous
  • Treatment Outcome
  • Vaccination
  • Viral Matrix Proteins/biosynthesis
  • Young Adult

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