Universal influenza A vaccine: Optimization of M2-based constructs

被引:186
作者
De Filette, M
Jou, WM
Birkett, A
Lyons, K
Schultz, B
Tonkyro, A
Resch, S
Fiers, W
机构
[1] Ghent Univ VIB, DMBR, B-9052 Ghent, Zwijnaarde, Belgium
[2] Apovia Inc, San Diego, CA 92121 USA
关键词
influenza A; M2-protein; hepatitis B virus; HBV core; M2e-HBc;
D O I
10.1016/j.virol.2005.04.004
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
We is the external domain of the influenza A M2-protein. It is minimally immunogenic during infection and conventional vaccination, which explains in part its striking sequence conservation across all human influenza A strains. Previous research has shown that when We is linked to an appropriate carrier such as hepatitis B virus core (HBc) particles, it becomes highly immunogenic, eliciting antibodies that fully protect mice against a potentially lethal virus infection. Different M2e-HBc particles and adjuvants suitable for human use were compared for induction of protective immunity. Strong immunogenicity and full protection were obtained after either intraperitoneal or intranasal administration. The most protective particle contained three consecutive M2e-copies linked to the N-terminus of HBc. Although HBc is highly immunogenic, the optimized M2e-HBc vaccine induced an anti-M2e antibody titer even higher than that of anti-HBc. (c) 2005 Elsevier Inc. All rights reserved.
引用
收藏
页码:149 / 161
页数:13
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