Vaccine-Induced Skewing of T Cell Responses Protects Against Chikungunya Virus Disease.


Journal

Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960

Informations de publication

Date de publication:
2019
Historique:
received: 07 08 2019
accepted: 16 10 2019
entrez: 19 11 2019
pubmed: 19 11 2019
medline: 21 10 2020
Statut: epublish

Résumé

Chikungunya virus (CHIKV) infections can cause severe and debilitating joint and muscular pain that can be long lasting. Current CHIKV vaccines under development rely on the generation of neutralizing antibodies for protection; however, the role of T cells in controlling CHIKV infection and disease is still unclear. Using an overlapping peptide library, we identified the CHIKV-specific T cell receptor epitopes recognized in C57BL/6 infected mice at 7 and 14 days post-infection. A fusion protein containing peptides 451, 416, a small region of nsP4, peptide 47, and an HA tag (CHKVf5) was expressed using adenovirus and cytomegalovirus-vectored vaccines. Mice vaccinated with CHKVf5 elicited robust T cell responses to higher levels than normally observed following CHIKV infection, but the vaccine vectors did not elicit neutralizing antibodies. CHKVf5-vaccinated mice had significantly reduced infectious viral load when challenged by intramuscular CHIKV injection. Depletion of both CD4

Identifiants

pubmed: 31736977
doi: 10.3389/fimmu.2019.02563
pmc: PMC6834551
doi:

Substances chimiques

Viral Vaccines 0

Types de publication

Journal Article Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

2563

Subventions

Organisme : NIAID NIH HHS
ID : R41 AI138964
Pays : United States
Organisme : NIAID NIH HHS
ID : R41AI138964-01
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI007472
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI142759
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI108725
Pays : United States

Informations de copyright

Copyright © 2019 Broeckel, Haese, Ando, Dmitriev, Kreklywich, Powers, Denton, Smith, Morrison, Heise, DeFilippis, Messaoudi, Curiel and Streblow.

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Auteurs

Rebecca M Broeckel (RM)

Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, OR, United States.

Nicole Haese (N)

Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, OR, United States.

Takeshi Ando (T)

Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, OR, United States.

Igor Dmitriev (I)

Department of Radiation Oncology, Washington University, St. Louis, MO, United States.

Craig N Kreklywich (CN)

Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, OR, United States.

John Powers (J)

Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, OR, United States.

Michael Denton (M)

Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, OR, United States.

Patricia Smith (P)

Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, OR, United States.

Thomas E Morrison (TE)

Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO, United States.

Mark Heise (M)

Department of Genetics, The University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.
Department of Microbiology and Immunology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.

Victor DeFilippis (V)

Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, OR, United States.

Ilhem Messaoudi (I)

Department of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, CA, United States.

David T Curiel (DT)

Department of Radiation Oncology, Washington University, St. Louis, MO, United States.

Daniel N Streblow (DN)

Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, OR, United States.
Division of Pathobiology and Immunology, Oregon National Primate Research Center, Beaverton, OR, United States.

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Classifications MeSH