PMID- 32956362
OWN - NLM
STAT- MEDLINE
DCOM- 20201102
LR  - 20201102
IS  - 1935-2735 (Electronic)
IS  - 1935-2727 (Print)
IS  - 1935-2727 (Linking)
VI  - 14
IP  - 9
DP  - 2020 Sep
TI  - Cross-serotypically conserved epitope recommendations for a universal T 
      cell-based dengue vaccine.
PG  - e0008676
LID - 10.1371/journal.pntd.0008676 [doi]
LID - e0008676
AB  - Dengue virus (DENV)-associated disease is a growing threat to public health 
      across the globe. Co-circulating as four different serotypes, DENV poses a unique 
      challenge for vaccine design as immunity to one serotype predisposes a person to 
      severe and potentially lethal disease upon infection from other serotypes. Recent 
      experimental studies suggest that an effective vaccine against DENV should elicit 
      a strong T cell response against all serotypes, which could be achieved by 
      directing T cell responses toward cross-serotypically conserved epitopes while 
      avoiding serotype-specific ones. Here, we used experimentally-determined DENV T 
      cell epitopes and patient-derived DENV sequences to assess the cross-serotypic 
      variability of the epitopes. We reveal a distinct near-binary pattern of epitope 
      conservation across serotypes for a large number of DENV epitopes. Based on the 
      conservation profile, we identify a set of 55 epitopes that are highly conserved 
      in at least 3 serotypes. Most of the highly conserved epitopes lie in 
      functionally important regions of DENV non-structural proteins. By considering 
      the global distribution of human leukocyte antigen (HLA) alleles associated with 
      these DENV epitopes, we identify a potentially robust subset of HLA class I and 
      class II restricted epitopes that can serve as targets for a universal T 
      cell-based vaccine against DENV while covering ~99% of the global population.
FAU - Ahmed, Syed Faraz
AU  - Ahmed SF
AUID- ORCID: 0000-0002-6086-0307
AD  - Department of Electronic and Computer Engineering, The Hong Kong University of 
      Science and Technology, Hong Kong, China.
FAU - Quadeer, Ahmed A
AU  - Quadeer AA
AD  - Department of Electronic and Computer Engineering, The Hong Kong University of 
      Science and Technology, Hong Kong, China.
FAU - Barton, John P
AU  - Barton JP
AUID- ORCID: 0000-0003-1467-421X
AD  - Department of Physics and Astronomy, University of California, Riverside, 
      California, United States of America.
FAU - McKay, Matthew R
AU  - McKay MR
AUID- ORCID: 0000-0002-8086-2545
AD  - Department of Electronic and Computer Engineering, The Hong Kong University of 
      Science and Technology, Hong Kong, China.
AD  - Department of Chemical and Biological Engineering, The Hong Kong University of 
      Science and Technology, Hong Kong, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200921
PL  - United States
TA  - PLoS Negl Trop Dis
JT  - PLoS neglected tropical diseases
JID - 101291488
RN  - 0 (Dengue Vaccines)
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (HLA Antigens)
RN  - 0 (Proteome)
SB  - IM
MH  - Cross Reactions/*immunology
MH  - Dengue/prevention & control
MH  - Dengue Vaccines/genetics/*immunology
MH  - Dengue Virus/immunology
MH  - Epitopes, T-Lymphocyte/*immunology
MH  - HLA Antigens/genetics/immunology
MH  - Humans
MH  - Models, Molecular
MH  - Protein Structure, Tertiary
MH  - Proteome
MH  - Sequence Analysis, Protein
MH  - Serogroup
MH  - T-Lymphocytes/*immunology
PMC - PMC7529213
COIS- The authors have declared that no competing interests exist.
EDAT- 2020/09/22 06:00
MHDA- 2020/11/03 06:00
PMCR- 2020/09/21
CRDT- 2020/09/21 17:14
PHST- 2019/12/05 00:00 [received]
PHST- 2020/08/04 00:00 [accepted]
PHST- 2020/10/01 00:00 [revised]
PHST- 2020/09/22 06:00 [pubmed]
PHST- 2020/11/03 06:00 [medline]
PHST- 2020/09/21 17:14 [entrez]
PHST- 2020/09/21 00:00 [pmc-release]
AID - PNTD-D-19-02058 [pii]
AID - 10.1371/journal.pntd.0008676 [doi]
PST - epublish
SO  - PLoS Negl Trop Dis. 2020 Sep 21;14(9):e0008676. doi: 
      10.1371/journal.pntd.0008676. eCollection 2020 Sep.