» Articles » PMID: 25050468

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.

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.

Citing Articles

mRNA-based therapeutics: powerful and versatile tools to combat diseases.

Qin S, Tang X, Chen Y, Chen K, Fan N, Xiao W Signal Transduct Target Ther. 2022; 7(1):166.

PMID: 35597779 PMC: 9123296. DOI: 10.1038/s41392-022-01007-w.


Antiviral Cell Products against COVID-19: Learning Lessons from Previous Research in Anti-Infective Cell-Based Agents.

Chikileva I, Shubina I, Burtseva A, Kirgizov K, Stepanyan N, Varfolomeeva S Biomedicines. 2022; 10(4).

PMID: 35453618 PMC: 9027720. DOI: 10.3390/biomedicines10040868.


An overview of the recent findings of cell-based therapies for the treatment and management of COVID-19.

Ghaffari S, Kazerooni H, Salehi-Najafabadi A Int Immunopharmacol. 2021; 101(Pt B):108226.

PMID: 34634685 PMC: 8492917. DOI: 10.1016/j.intimp.2021.108226.


An outlook on antigen-specific adoptive immunotherapy for viral infections with a focus on COVID-19.

Monzavi S, Naderi M, Ahmadbeigi N, Kajbafzadeh A, Muhammadnejad S Cell Immunol. 2021; 367:104398.

PMID: 34217004 PMC: 8214814. DOI: 10.1016/j.cellimm.2021.104398.


A Guide to Nucleic Acid Vaccines in the Prevention and Treatment of Infectious Diseases and Cancers: From Basic Principles to Current Applications.

Qin F, Xia F, Chen H, Cui B, Feng Y, Zhang P Front Cell Dev Biol. 2021; 9:633776.

PMID: 34113610 PMC: 8185206. DOI: 10.3389/fcell.2021.633776.


References
1.
Boeckh M, Leisenring W, Riddell S, Bowden R, Huang M, Myerson D . Late cytomegalovirus disease and mortality in recipients of allogeneic hematopoietic stem cell transplants: importance of viral load and T-cell immunity. Blood. 2002; 101(2):407-14. DOI: 10.1182/blood-2002-03-0993. View

2.
Moodie Z, Price L, Gouttefangeas C, Mander A, Janetzki S, Lower M . Response definition criteria for ELISPOT assays revisited. Cancer Immunol Immunother. 2010; 59(10):1489-501. PMC: 2909425. DOI: 10.1007/s00262-010-0875-4. View

3.
Van Camp K, Cools N, Stein B, Van de Velde A, Goossens H, Berneman Z . Efficient mRNA electroporation of peripheral blood mononuclear cells to detect memory T cell responses for immunomonitoring purposes. J Immunol Methods. 2010; 354(1-2):1-10. DOI: 10.1016/j.jim.2010.01.009. View

4.
Beam E, Razonable R . Cytomegalovirus in solid organ transplantation: epidemiology, prevention, and treatment. Curr Infect Dis Rep. 2012; 14(6):633-41. DOI: 10.1007/s11908-012-0292-2. View

5.
Einsele H, Roosnek E, Rufer N, Sinzger C, Riegler S, Loffler J . Infusion of cytomegalovirus (CMV)-specific T cells for the treatment of CMV infection not responding to antiviral chemotherapy. Blood. 2002; 99(11):3916-22. DOI: 10.1182/blood.v99.11.3916. View