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

使用信使 RNA 转染的树突状细胞接种疫苗,在健康志愿者和同种异体干细胞接受者中诱导巨细胞病毒特异性 T 细胞反应

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作者: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

Background

Infection with human cytomegalovirus (CMV) is a significant cause of morbidity and mortality in solid organ and hematopoietic stem cell transplant (HSCT) recipients.

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.

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.

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