PMID- 34944678
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20211229
IS  - 2227-9059 (Print)
IS  - 2227-9059 (Electronic)
IS  - 2227-9059 (Linking)
VI  - 9
IP  - 12
DP  - 2021 Dec 8
TI  - A Novel Orf Virus D1701-VrV-Based Dengue Virus (DENV) Vaccine Candidate 
      Expressing HLA-Specific T Cell Epitopes: A Proof-of-Concept Study.
LID - 10.3390/biomedicines9121862 [doi]
LID - 1862
AB  - Although dengue virus (DENV) affects almost half of the world's population there 
      are neither preventive treatments nor any long-lasting and protective vaccines 
      available at this time. The complexity of the protective immune response to DENV 
      is still not fully understood. The most advanced vaccine candidates focus 
      specifically on humoral immune responses and the production of virus-neutralizing 
      antibodies. However, results from several recent studies have revealed the 
      protective role of T cells in the immune response to DENV. Hence, in this study, 
      we generated a novel and potent DENV vaccine candidate based on an Orf virus 
      (ORFV, genus Parapoxvirus) vector platform engineered to encode five highly 
      conserved or cross-reactive DENV human leukocyte antigen (HLA)-A*02- or 
      HLA-B*07-restricted epitopes as minigenes (ORFV-DENV). We showed that ORFV-DENV 
      facilitates the in vitro priming of CD8(+) T cells from healthy blood donors 
      based on responses to each of the encoded immunogenic peptides. Moreover, we 
      demonstrated that peripheral blood mononuclear cells isolated from clinically 
      confirmed DENV-positive donors stimulated with ORFV-DENV generate cytotoxic T 
      cell responses to at least three of the expressed DENV peptides. Finally, we 
      showed that ORFV-DENV could activate CD8(+) T cells isolated from donors who had 
      recovered from Zika virus (ZIKV) infection. ZIKV belongs to the same virus family 
      (Flaviviridae) and has epitope sequences that are homologous to those of DENV. We 
      found that highly conserved HLA-B*07-restricted ZIKV and DENV epitopes induced 
      functional CD8(+) T cell responses in PBMCs isolated from confirmed ZIKV-positive 
      donors. In summary, this proof-of-concept study characterizes a promising new 
      ORFV D1701-VrV-based DENV vaccine candidate that induces broad and functional 
      epitope-specific CD8(+) T cell responses.
FAU - Reguzova, Alena
AU  - Reguzova A
AD  - Department of Immunology, Interfaculty Institute for Cell Biology, University of 
      Tubingen, 72076 Tubingen, Germany.
FAU - Fischer, Nico
AU  - Fischer N
AD  - Department of Infectious Diseases, Heidelberg Institute of Global Health (HIGH) & 
      Tropical Medicine, Heidelberg University Hospital, 69120 Heidelberg, Germany.
FAU - Muller, Melanie
AU  - Muller M
AD  - Department of Immunology, Interfaculty Institute for Cell Biology, University of 
      Tubingen, 72076 Tubingen, Germany.
FAU - Salomon, Ferdinand
AU  - Salomon F
AD  - Department of Immunology, Interfaculty Institute for Cell Biology, University of 
      Tubingen, 72076 Tubingen, Germany.
FAU - Jaenisch, Thomas
AU  - Jaenisch T
AD  - Department of Infectious Diseases, Heidelberg Institute of Global Health (HIGH) & 
      Tropical Medicine, Heidelberg University Hospital, 69120 Heidelberg, Germany.
FAU - Amann, Ralf
AU  - Amann R
AD  - Department of Immunology, Interfaculty Institute for Cell Biology, University of 
      Tubingen, 72076 Tubingen, Germany.
LA  - eng
GR  - 03EFKBW171/Federal Ministry for Economic Affairs and Energy/
GR  - Deutsche Forschungsgemeinschaft ZUK63/Institutional Strategy of the University of 
      Tuebingen/
PT  - Journal Article
DEP - 20211208
PL  - Switzerland
TA  - Biomedicines
JT  - Biomedicines
JID - 101691304
PMC - PMC8698572
OTO - NOTNLM
OT  - CD8+ T cells
OT  - HLA class I
OT  - ORFV
OT  - T cell epitope
OT  - dengue virus
OT  - immune response
OT  - parapoxvirus
OT  - vaccine
OT  - viral vector
COIS- R.A. is the inventor of patents on ORFV. R.A., M.M. and F.S. have ownership 
      interests in Prime Vector Technologies GmbH.
EDAT- 2021/12/25 06:00
MHDA- 2021/12/25 06:01
PMCR- 2021/12/08
CRDT- 2021/12/24 01:06
PHST- 2021/10/23 00:00 [received]
PHST- 2021/12/01 00:00 [revised]
PHST- 2021/12/02 00:00 [accepted]
PHST- 2021/12/24 01:06 [entrez]
PHST- 2021/12/25 06:00 [pubmed]
PHST- 2021/12/25 06:01 [medline]
PHST- 2021/12/08 00:00 [pmc-release]
AID - biomedicines9121862 [pii]
AID - biomedicines-09-01862 [pii]
AID - 10.3390/biomedicines9121862 [doi]
PST - epublish
SO  - Biomedicines. 2021 Dec 8;9(12):1862. doi: 10.3390/biomedicines9121862.