Development of a universal influenza A vaccine based on the M2e peptide fused to the papaya mosaic virus (PapMV) vaccine platform

被引:155
作者
Denis, Jerome [1 ]
Acosta-Ramirez, Elizabeth [1 ,2 ]
Zhao, Yinghi [1 ]
Hamelin, Marie-Eve [1 ]
Koukavica, Irena [1 ]
Baz, Mariana [1 ]
Abed, Yacine [1 ]
Savard, Christian [1 ]
Pare, Christine [1 ]
Macias, Constantino Lopez [2 ]
Boivin, Guy [1 ]
Leclerc, Denis [1 ]
机构
[1] Univ Laval, Pavillon CHUL, Ctr Rech & Infectiol, Quebec City, PQ G1V 4G2, Canada
[2] 1er Piso Hosp Especialidades, Ctr Med Nacl Siglo 21, IMSS, Unidad Invest Med & Inmunoquim, Mexico City, DF, Mexico
基金
加拿大自然科学与工程研究理事会; 加拿大健康研究院;
关键词
papaya mosaic virus (PapMV); virus-like particles (VLPs); influenza A M2e peptide;
D O I
10.1016/j.vaccine.2008.04.052
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
With the emergence of highly virulent influenza viruses and the consequent risk of pandernics, new approaches to designing universal influenza vaccines are urgently needed. In this report, we demonstrate the potential of using a papaya mosaic virus (PapMV) platform carrying the universal M2e influenza epitope (PapMV-CP-M2e) as a candidate flu vaccine. We show that PapMV-CP-M2e virus-like particles (VLPs) can induce production in mice of anti-M2e antibodies that can recognize influenza-infected cells. PapMVCP-M2e discs made of 20 coat protein (CP) subunits were shown to be poorly immunogenic compared to PapMV-CP-M2e VLPs composed of several hundred CP subunits. We also show that addition of either alum or PapMV-CP VLPs as adjuvant dramatically increased the immunogenicity of PapMV-CP-M2e-containing vaccine, and led to 100% protection against a challenge of 4LD50 with the WSN/33 strain. These results show, for the first time, the potential of a recombinant plant virus protein to serve as both peptide delivery system and adjuvant in the crucial field of influenza vaccine development. (c) 2008 Elsevier Ltd. All rights reserved.
引用
收藏
页码:3395 / 3403
页数:9
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