PMID- 25111185
OWN - NLM
STAT- MEDLINE
DCOM- 20150417
LR  - 20231110
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 9
IP  - 8
DP  - 2014
TI  - Dendritic cell-mediated, DNA-based vaccination against hepatitis C induces the 
      multi-epitope-specific response of humanized, HLA transgenic mice.
PG  - e104606
LID - 10.1371/journal.pone.0104606 [doi]
LID - e104606
AB  - 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-gamma 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-alpha 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.
FAU - Mishra, Sasmita
AU  - Mishra S
AD  - Department of Medicine, Rhode Island Hospital and the Warren Alpert Medical 
      School of Brown University, Providence, Rhode Island, United States of America.
FAU - Lavelle, Bianca J
AU  - Lavelle BJ
AD  - Department of Medicine, Rhode Island Hospital and the Warren Alpert Medical 
      School of Brown University, Providence, Rhode Island, United States of America.
FAU - Desrosiers, Joe
AU  - Desrosiers J
AD  - Institute for Immunology and Informatics, University of Rhode Island, Providence, 
      Rhode Island, United States of America.
FAU - Ardito, Matt T
AU  - Ardito MT
AD  - EpiVax, Inc., Providence, Rhode Island, United States of America.
FAU - Terry, Frances
AU  - Terry F
AD  - EpiVax, Inc., Providence, Rhode Island, United States of America.
FAU - Martin, William D
AU  - Martin WD
AD  - EpiVax, Inc., Providence, Rhode Island, United States of America.
FAU - De Groot, Anne S
AU  - De Groot AS
AD  - Institute for Immunology and Informatics, University of Rhode Island, Providence, 
      Rhode Island, United States of America; EpiVax, Inc., Providence, Rhode Island, 
      United States of America.
FAU - Gregory, Stephen H
AU  - Gregory SH
AD  - Department of Medicine, Rhode Island Hospital and the Warren Alpert Medical 
      School of Brown University, Providence, Rhode Island, United States of America.
LA  - eng
GR  - U19 AI082642/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20140811
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (CD11c Antigen)
RN  - 0 (Epitopes)
RN  - 0 (HLA-A2 Antigen)
RN  - 0 (HLA-DRB1 Chains)
RN  - 0 (Pdcd1 protein, mouse)
RN  - 0 (Programmed Cell Death 1 Receptor)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Vaccines, DNA)
RN  - 0 (Vaccines, Subunit)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Animals
MH  - CD11c Antigen/metabolism
MH  - Dendritic Cells/*immunology/metabolism
MH  - Epitopes/*immunology
MH  - Female
MH  - HLA-A2 Antigen/genetics
MH  - HLA-DRB1 Chains/genetics
MH  - Hepacivirus/*immunology
MH  - Hepatitis C/*prevention & control
MH  - Humans
MH  - Interferon-gamma/biosynthesis
MH  - Mice
MH  - Mice, Transgenic
MH  - Programmed Cell Death 1 Receptor/metabolism
MH  - Spleen/immunology
MH  - Tumor Necrosis Factor-alpha/biosynthesis
MH  - Vaccination/*methods
MH  - Vaccines, DNA/genetics/*immunology
MH  - Vaccines, Subunit/genetics/immunology
PMC - PMC4128787
COIS- Competing Interests: Anne De Groot and William Martin are senior officers and 
      majority shareholders at EpiVax, Inc. Matt Ardito and Frances Terry are also 
      employed at EpiVax, Inc. These authors acknowledge a potential conflict of 
      interest and attest that the work contained in this report is free of any bias 
      that might be associated with the commercial goals of the company. There are no 
      patents, products in development or marketed products to declare. This does not 
      alter their adherence to all the PLOS ONE policies on sharing data and materials.
EDAT- 2014/08/12 06:00
MHDA- 2015/04/18 06:00
PMCR- 2014/08/11
CRDT- 2014/08/12 06:00
PHST- 2014/04/02 00:00 [received]
PHST- 2014/06/29 00:00 [accepted]
PHST- 2014/08/12 06:00 [entrez]
PHST- 2014/08/12 06:00 [pubmed]
PHST- 2015/04/18 06:00 [medline]
PHST- 2014/08/11 00:00 [pmc-release]
AID - PONE-D-14-14837 [pii]
AID - 10.1371/journal.pone.0104606 [doi]
PST - epublish
SO  - PLoS One. 2014 Aug 11;9(8):e104606. doi: 10.1371/journal.pone.0104606. 
      eCollection 2014.