PMID- 28575582
OWN - NLM
STAT- MEDLINE
DCOM- 20180709
LR  - 20181202
IS  - 2164-554X (Electronic)
IS  - 2164-5515 (Print)
IS  - 2164-5515 (Linking)
VI  - 13
IP  - 12
DP  - 2017 Dec 2
TI  - An immunoinformatics-derived DNA vaccine encoding human class II T cell epitopes 
      of Ebola virus, Sudan virus, and Venezuelan equine encephalitis virus is 
      immunogenic in HLA transgenic mice.
PG  - 2824-2836
LID - 10.1080/21645515.2017.1329788 [doi]
AB  - Immunoinformatics tools were used to predict human leukocyte antigen (HLA) class 
      II-restricted T cell epitopes within the envelope glycoproteins and nucleocapsid 
      proteins of Ebola virus (EBOV) and Sudan virus (SUDV) and the structural proteins 
      of Venezuelan equine encephalitis virus (VEEV). Selected epitopes were tested for 
      binding to soluble HLA molecules representing 5 class II alleles (DRB1*0101, 
      DRB1*0301, DRB1*0401, DRB1*0701, and DRB1*1501). All but one of the 25 tested 
      peptides bound to at least one of the DRB1 alleles, and 4 of the peptides bound 
      at least moderately or weakly to all 5 DRB1 alleles. Additional algorithms were 
      used to design a single "string-of-beads" expression construct with 44 selected 
      epitopes arranged to avoid creation of spurious junctional epitopes. Seventeen of 
      these 44 predicted epitopes were conserved between the major histocompatibility 
      complex (MHC) of humans and mice, allowing initial testing in mice. BALB/c mice 
      vaccinated with the multi-epitope construct developed statistically significant 
      cellular immune responses to EBOV, SUDV, and VEEV peptides as measured by 
      interferon (IFN)-gamma ELISpot assays. Significant levels of antibodies to VEEV, but 
      not EBOV, were also detected in vaccinated BALB/c mice. To assess immunogenicity 
      in the context of a human MHC, HLA-DR3 transgenic mice were vaccinated with the 
      multi-epitope construct and boosted with a mixture of the 25 peptides used in the 
      binding assays. The vaccinated HLA-DR3 mice developed significant cellular immune 
      responses to 4 of the 25 (16%) tested individual class II peptides as measured by 
      IFN-gamma ELISpot assays. In addition, these mice developed antibodies against EBOV 
      and VEEV as measured by ELISA. While a low but significant level of protection 
      was observed in vaccinated transgenic mice after aerosol exposure to VEEV, no 
      protection was observed after intraperitoneal challenge with mouse-adapted EBOV. 
      These studies provide proof of concept for the use of an informatics approach to 
      design a multi-agent, multi-epitope immunogen and provide a basis for further 
      testing aimed at focusing immune responses toward desired protective T cell 
      epitopes.
FAU - Bounds, Callie E
AU  - Bounds CE
AD  - a United States Army Medical Research Institute of Infectious Diseases , Fort 
      Detrick , MD , USA.
FAU - Terry, Frances E
AU  - Terry FE
AD  - b EpiVax, Inc. , Providence , RI , USA.
FAU - Moise, Leonard
AU  - Moise L
AUID- ORCID: 0000-0002-4410-865X
AD  - b EpiVax, Inc. , Providence , RI , USA.
AD  - c Institute for Immunology and Informatics , University of Rhode Island , 
      Providence , RI , USA.
FAU - Hannaman, Drew
AU  - Hannaman D
AD  - d Ichor Medical Systems, Inc. , San Diego , CA , USA.
FAU - Martin, William D
AU  - Martin WD
AD  - b EpiVax, Inc. , Providence , RI , USA.
FAU - De Groot, Anne S
AU  - De Groot AS
AUID- ORCID: 0000-0001-5911-1459
AD  - b EpiVax, Inc. , Providence , RI , USA.
AD  - c Institute for Immunology and Informatics , University of Rhode Island , 
      Providence , RI , USA.
FAU - Suschak, John J
AU  - Suschak JJ
AD  - a United States Army Medical Research Institute of Infectious Diseases , Fort 
      Detrick , MD , USA.
FAU - Dupuy, Lesley C
AU  - Dupuy LC
AD  - a United States Army Medical Research Institute of Infectious Diseases , Fort 
      Detrick , MD , USA.
FAU - Schmaljohn, Connie S
AU  - Schmaljohn CS
AD  - a United States Army Medical Research Institute of Infectious Diseases , Fort 
      Detrick , MD , USA.
LA  - eng
PT  - Journal Article
DEP - 20170602
PL  - United States
TA  - Hum Vaccin Immunother
JT  - Human vaccines & immunotherapeutics
JID - 101572652
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (Vaccines, DNA)
RN  - 0 (Viral Vaccines)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Animals
MH  - Ebolavirus/genetics/*immunology
MH  - Encephalitis Virus, Venezuelan Equine/genetics/*immunology
MH  - Enzyme-Linked Immunospot Assay
MH  - Epitopes, T-Lymphocyte/genetics/*immunology
MH  - Female
MH  - Histocompatibility Antigens Class II/genetics/*metabolism
MH  - Humans
MH  - Interferon-gamma/metabolism
MH  - Mice, Inbred BALB C
MH  - Mice, Transgenic
MH  - Protein Binding
MH  - T-Lymphocytes/immunology
MH  - Vaccines, DNA/administration & dosage/genetics/*immunology
MH  - Viral Vaccines/administration & dosage/genetics/*immunology
PMC - PMC5718811
OTO - NOTNLM
OT  - DNA vaccine
OT  - EBOV
OT  - Ebola virus
OT  - SUDV
OT  - Sudan virus
OT  - T cell epitope
OT  - VEEV
OT  - Venezuelan equine encephalitis virus
OT  - epitope-based vaccine
OT  - genome-derived vaccine
OT  - mice
OT  - peptide vaccine
EDAT- 2017/06/03 06:00
MHDA- 2018/07/10 06:00
PMCR- 2017/06/02
CRDT- 2017/06/03 06:00
PHST- 2017/06/03 06:00 [pubmed]
PHST- 2018/07/10 06:00 [medline]
PHST- 2017/06/03 06:00 [entrez]
PHST- 2017/06/02 00:00 [pmc-release]
AID - 1329788 [pii]
AID - 10.1080/21645515.2017.1329788 [doi]
PST - ppublish
SO  - Hum Vaccin Immunother. 2017 Dec 2;13(12):2824-2836. doi: 
      10.1080/21645515.2017.1329788. Epub 2017 Jun 2.