Vaccinia-based influenza vaccine overcomes previously induced immunodominance hierarchy for heterosubtypic protection.
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.
Vaccine II, Mogam Biotechnology Research Institute, Yongin Si, Republic of Korea.
Ji-Sun
JS
Kwon
Jungsoon
J
Yoon
Yeon-Jung
YJ
Kim
Kyuho
K
Kang
Sunje
S
Woo
Dea-Im
DI
Jung
Man Ki
MK
Song
Eun-Ha
EH
Kim
Hyeok-Il
HI
Kwon
Young Ki
YK
Choi
Jihye
J
Kim
Jeewon
J
Lee
Yeup
Y
Yoon
Eui-Cheol
EC
Shin
Jin-Won
JW
Youn
D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology; D007252:Influenza Vaccines / Q000276:immunology* / Q000494:pharmacology*; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control; D013552:Swine; D013601:T-Lymphocytes / Q000276:immunology; D014615:Vaccinia / Q000276:immunology; D014616:Vaccinia virus / Q000276:immunology*
D007252:Influenza Vaccines
Consensus sequence; Heterosubtypic protection; Immunodominance hierarchy; T-cell immunity; Universal influenza vaccine