T Cell Responses Induced by Attenuated Flavivirus Vaccination Are Specific and Show Limited Cross-Reactivity with Other Flavivirus Species.
Adolescent
Adult
Antibodies, Neutralizing
/ immunology
Antibodies, Viral
/ immunology
CD4-Positive T-Lymphocytes
CD8-Positive T-Lymphocytes
/ immunology
Cross Reactions
/ immunology
Dengue
/ immunology
Dengue Vaccines
/ immunology
Dengue Virus
/ immunology
Encephalitis, Japanese
/ immunology
Epitopes, T-Lymphocyte
/ genetics
Female
Flavivirus
/ immunology
Flavivirus Infections
/ immunology
Humans
Leukocytes, Mononuclear
/ immunology
Male
Middle Aged
Sequence Homology
Vaccination
Vaccines, Attenuated
/ immunology
Viral Vaccines
/ immunology
West Nile Fever
/ immunology
Yellow Fever
/ immunology
Yellow Fever Vaccine
Yellow fever virus
/ immunology
Young Adult
Zika Virus
/ immunology
Zika Virus Infection
/ immunology
DENV
T cells
YFV
flaviviruses
vaccines
Journal
Journal of virology
ISSN: 1098-5514
Titre abrégé: J Virol
Pays: United States
ID NLM: 0113724
Informations de publication
Date de publication:
04 05 2020
04 05 2020
Historique:
received:
17
01
2020
accepted:
25
02
2020
pubmed:
7
3
2020
medline:
27
10
2020
entrez:
6
3
2020
Statut:
epublish
Résumé
Members of the flavivirus genus share a high level of sequence similarity and often circulate in the same geographical regions. However, whether T cells induced by one viral species cross-react with other related flaviviruses has not been globally addressed. In this study, we tested pools of epitopes derived from dengue (DENV), Zika (ZIKV), Japanese encephalitis (JEV), West Nile (WNV), and yellow fever (YFV) viruses by intracellular cytokine staining (ICS) using peripheral blood mononuclear cells (PBMCs) of individuals naturally exposed to DENV or immunized with DENV (TV005) or YF17D vaccine. CD8 T cell responses recognized epitopes from multiple flaviviruses; however, the magnitude of cross-reactive responses was consistently severalfold lower than those to the autologous epitope pools and was associated with lower expression of activation markers such as CD40L, CD69, and CD137. Next, we characterized the antigen sensitivity of short-term T cell lines (TCL) representing 29 different individual epitope/donor combinations. TCL derived from DENV monovalent vaccinees induced CD8 and CD4 T cells that cross-reacted within the DENV serocomplex but were consistently associated with >100-fold-lower antigen sensitivity for most other flaviviruses, with no cross-recognition of YFV-derived peptides. CD8 and CD4 TCL from YF17D vaccinees were associated with very limited cross-reactivity with any other flaviviruses and in five out of eight cases >1,000-fold-lower antigen sensitivity. Overall, our data suggest limited cross-reactivity for both CD4 and CD8 T cell responses between flaviviruses and have implications for understanding immunity elicited by natural infection and strategies to develop live attenuated vaccines against flaviviral species.
Identifiants
pubmed: 32132233
pii: JVI.00089-20
doi: 10.1128/JVI.00089-20
pmc: PMC7199411
pii:
doi:
Substances chimiques
Antibodies, Neutralizing
0
Antibodies, Viral
0
Dengue Vaccines
0
Epitopes, T-Lymphocyte
0
Vaccines, Attenuated
0
Viral Vaccines
0
Yellow Fever Vaccine
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIAID NIH HHS
ID : HHSN272200900042C
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI106695
Pays : United States
Organisme : NIAID NIH HHS
ID : HHSN272201400045C
Pays : United States
Organisme : NIAID NIH HHS
ID : HHSN272200900010C
Pays : United States
Organisme : NIAID NIH HHS
ID : HHSN272200900045C
Pays : United States
Informations de copyright
Copyright © 2020 American Society for Microbiology.
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