tetano
Editor, Senior Moderator
Eur J Immunol. 2014 May 13. doi: 10.1002/eji.201344005. [Epub ahead of print]
Vaccinia-based influenza vaccine overcomes previously induced immunodominance hierarchy for heterosubtypic protection.
Kwon JS1, Yoon J, Kim YJ, Kang K, Woo S, Jung DI, Song MK, Kim EH, Kwon HI, Choi YK, Kim J, Lee J, Yoon Y, Shin EC, Youn JW.
Author information
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 HPAI 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. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
KEYWORDS:
T-cell immunity, Universal influenza vaccine, consensus sequence, heterosubtypic protection, immunodominance hierarchy
PMID:
24825439
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24825439
Vaccinia-based influenza vaccine overcomes previously induced immunodominance hierarchy for heterosubtypic protection.
Kwon JS1, Yoon J, Kim YJ, Kang K, Woo S, Jung DI, Song MK, Kim EH, Kwon HI, Choi YK, Kim J, Lee J, Yoon Y, Shin EC, Youn JW.
Author information
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 HPAI 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. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
KEYWORDS:
T-cell immunity, Universal influenza vaccine, consensus sequence, heterosubtypic protection, immunodominance hierarchy
PMID:
24825439
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24825439