Vaccinia-based influenza vaccine overcomes previously induced immunodominance hierarchy for heterosubtypic protection
- Authors
- Kwon J.-S.[Kwon J.-S.]; Yoon J.[Yoon J.]; Kim Y.-J.[Kim Y.-J.]; Kang K.[Kang K.]; Woo S.[Woo S.]; Jung D.-I.[Jung D.-I.]; Song M.K.[Song M.K.]; Kim E.-H.[Kim E.-H.]; Kwon H.-il.[Kwon H.-il.]; Choi Y.K.[Choi Y.K.]; Kim J.[Kim J.]; Lee J.[Lee J.]; Yoon Y.[Yoon Y.]; Shin E.-C.[Shin E.-C.]; Youn J.-W.[Youn J.-W.]
- Issue Date
- 2014
- Keywords
- Consensus sequence; Heterosubtypic protection; Immunodominance hierarchy; T-cell immunity; Universal influenza vaccine
- Citation
- European Journal of Immunology, v.44, no.8, pp.2360 - 2369
- Indexed
- SCIE
SCOPUS
- Journal Title
- European Journal of Immunology
- Volume
- 44
- Number
- 8
- Start Page
- 2360
- End Page
- 2369
- URI
- https://scholarworks.bwise.kr/skku/handle/2021.sw.skku/57537
- DOI
- 10.1002/eji.201344005
- ISSN
- 1521-4141
- Abstract
- Growing concerns about unpredictable influenza pandemics require a broadly protective vaccine against diverse influenza strains. One of the promising approaches was a T cell-based vaccine, but the narrow breadth of T-cell immunity due to the immunodominance hierarchy established by previous influenza infection and efficacy against only mild challenge condition are important hurdles to overcome. To model T-cell immunodominance hierarchy in humans in an experimental setting, influenza-primed C57BL/6 mice were chosen and boosted with a mixture of vaccinia recombinants, individually expressing consensus sequences from avian, swine, and human isolates of influenza internal proteins. As determined by IFN-γ ELISPOT and polyfunctional cytokine secretion, the vaccinia recombinants of influenza expanded the breadth of T-cell responses to include subdominant and even minor epitopes. Vaccine groups were successfully protected against 100 LD50 challenges with PR/8/34 and highly pathogenic avian influenza H5N1, which contained the identical dominant NP366 epitope. Interestingly, in challenge with pandemic A/Cal/04/2009 containing mutations in the dominant epitope, only the group vaccinated with rVV-NP + PA showed improved protection. Taken together, a vaccinia-based influenza vaccine expressing conserved internal proteins improved the breadth of influenza-specific T-cell immunity and provided heterosubtypic protection against immunologically close as well as distant influenza strains. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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Collections - Samsung Advanced Institute for Health Sciences and Technology, SKKU > Samsung Advanced Institute for Health Sciences and Technology, SKKU > 1. Journal Articles
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