Dendritic Cell-Mediated, DNA-Based Vaccination Against Hepatitis C Induces the Multi-Epitope-Specific Response of Humanized, HLA Transgenic Mice

Authors

Sasmita Mishra
Bianca J. Lavelle
Joe Desrosiers
Matt T. Ardito
Frances Terry
William D. Martin
Anne S. De Groot, University of Rhode IslandFollow
Stephen H. Gregory

Document Type

Article

Date of Original Version

8-11-2014

Abstract

Hepatitis C virus (HCV) is the etiologic agent of chronic liver disease, hepatitis C. Spontaneous resolution of viral infection is associated with vigorous HLA class I- and class II-restricted T cell responses to multiple viral epitopes. Unfortunately, only 20% of patients clear infection spontaneously, most develop chronic disease and require therapy. The response to chemotherapy varies, however; therapeutic vaccination offers an additional treatment strategy. To date, therapeutic vaccines have demonstrated only limited success. Vector-mediated vaccination with multi-epitope-expressing DNA constructs alone or in combination with chemotherapy offers an additional treatment approach. Gene sequences encoding validated HLA-A2- and HLA-DRB1-restricted epitopes were synthesized and cloned into an expression vector. Dendritic cells (DCs) derived from humanized, HLA-A2/DRB1 transgenic (donor) mice were transfected with these multi-epitope-expressing DNA constructs. Recipient HLA-A2/DRB1 mice were vaccinated s.c. with transfected DCs; control mice received non-transfected DCs. Peptide-specific IFN-γ production by splenic T cells obtained at 5 weeks post-immunization was quantified by ELISpot assay; additionally, the production of IL-4, IL-10 and TNF-α were quantified by cytokine bead array. Splenocytes derived from vaccinated HLA-A2/DRB1 transgenic mice exhibited peptide-specific cytokine production to the vast majority of the vaccine-encoded HLA class I- and class II-restricted T cell epitopes. A multi-epitope-based HCV vaccine that targets DCs offers an effective approach to inducing a broad immune response and viral clearance in chronic, HCV-infected patients.

Citation/Publisher Attribution

Mishra S., Lavelle B.J., Desrosiers J., Ardito M.T., Terry F., Martin W.D., De Groot A.S., Gregory S.H. (2014). "Dendritic cell-mediated, DNA-based vaccination against hepatitis C induces the multi-epitope-specific response of humanized, HLA transgenic mice." PLoS One. 9(8).

Available at: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0104606.

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This work is licensed under a Creative Commons Attribution 4.0 License.