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Induction of Cytomegalovirus-Specific T Cell Responses in Healthy Volunteers and Allogeneic Stem Cell Recipients Using Vaccination With Messenger RNA–Transfected Dendritic Cells

Van Craenenbroeck, Amaryllis H.1,2; Smits, Evelien L.J.3,4; Anguille, Sébastien3,4; Van de Velde, Ann5; Stein, Barbara4; Braeckman, Tessa6; Van Camp, Kirsten3; Nijs, Griet4; Ieven, Margareta7; Goossens, Herman7; Berneman, Zwi N.3,4,5; Van Tendeloo, Viggo F.I.3; Verpooten, Gert A.1,2; Van Damme, Pierre6; Cools, Nathalie3

doi: 10.1097/TP.0000000000000272
Clinical Science

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.

An early safety study of mRNA loaded monocyte derived dendritic cells as a vaccine for protection against cytomegalovirus has shown promising early results with measurable in vivo response to the vaccine and no adverse safety signals.

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.

Received 17 December 2013. Revision requested 14 January 2014.

Accepted 25 April 2014.

The authors declare no conflicts of interest.

E.L.J.S. is supported by the Research Foundation Flanders (FWO). S.A. was supported by the Research Foundation Flanders (FWO). K.V.C. was supported by an Interuniversity Attraction Pole project (IAP P6/41) of theBelgian Science Policy. Z.B. is PI of a research grant of the Foundation against Cancer (Stichting tegen Kanker) and of an Interuniversity Attraction Pole project (IAP P6/41) of the Belgian Science Policy. ZB is co-PI of the Methusalem program of the Flemish Government. V.V.T. is co-PI of a research grant of the Foundation against Cancer (Stichting tegen Kanker). P.V.D. is co-PI of the Methusalem program of the Flemish Government. N.C. is supported by the Research Foundation Flanders (FWO). EudraCT number: 2008-006074-15 and 2008-000430-45.

A.H.V.C. participated in research design and writing of the article. E.L.J.S. participated in writing of the article. S.A. participated in writing of the article, performance of the research and data analysis. A.V.d.V. participated in the performance of the research. B.S. participated in the performance of the research and data analysis. T.B. participated in the performance of the research. K.V.C. participated in the performance of the research and data analysis. G.N. participated in the performance of the research. M.I. participated in the performance of the research and data analysis. H.G. participated in the performance of the research. Z.N.B. participated in research design and writing of the article. V.F.I.V.T. participated in research design and writing of the article. G.A.V. participated in research design and writing of the article. P.V.D. participated in research design and performance of the research. N.C. participated in research design, performance of the research, data analysis and writing of the article.

Correspondence: Nathalie Cools, Ph.D., Antwerp University Hospital (UZA), Wilrijkstraat 10, B-2650 Edegem, Belgium. (Nathalie.cools@uza.be)

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Accepted July 22, 2014

© 2015 by Lippincott Williams & Wilkins