Induction of Cytomegalovirus-specific T Cell Responses in Healthy Volunteers and Allogeneic Stem Cell Recipients Using Vaccination with Messenger RNA-transfected Dendritic Cells
Overview
Authors
Affiliations
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.
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.
Chikileva I, Shubina I, Burtseva A, Kirgizov K, Stepanyan N, Varfolomeeva S Biomedicines. 2022; 10(4).
PMID: 35453618 PMC: 9027720. DOI: 10.3390/biomedicines10040868.
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.
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.