A consensus-hemagglutinin-based DNA vaccine that protects mice against divergent H5N1 influenza viruses

被引:133
作者
Chen, Ming-Wei [1 ,3 ]
Cheng, Ting-Jen Rachel [1 ]
Huang, Yaoxing [2 ]
Jan, Jia-Tsrong [1 ]
Ma, Shiou-Hwa [1 ]
Yu, Alice L. [1 ]
Wong, Chi-Huey [1 ]
Ho, David D. [1 ,2 ]
机构
[1] Acad Sinica, Genom Res Ctr, Taipei 115, Taiwan
[2] Rockefeller Univ, Aaron Diamond AIDS Res Ctr, New York, NY 10016 USA
[3] Natl Yang Ming Univ, Inst Biochem & Mol Biol, Taipei 112, Taiwan
关键词
D O I
10.1073/pnas.0806901105
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
H5N1 influenza viruses have spread extensively among wild birds and domestic poultry. Cross-species transmission of these viruses to humans has been documented in over 380 cases, with a mortality rate of approximate to 60%. There is great concern that a H5N1 virus would acquire the ability to spread efficiently between humans, thereby becoming a pandernic threat. An H5N1 influenza vaccine must, therefore, be an integral part of any pandernic preparedness plan. However, traditional methods of making influenza vaccines have yet to produce a candidate that could induce potently neutralizing antibodies against divergent strains of H5N1 influenza viruses. To address this need, we generated a consensus H5N1 hemagglutinin (HA) sequence based on data available in early 2006. This sequence was then optimized for protein expression before being inserted into a DNA plasmid (pCHA5). Immunizing mice with pCHA5, delivered intramuscularly via electroporation, elicited antibodies that neutralized a panel of virions that have been pseuclotyped with the HA from various H5N1 viruses (clades 1, 2.1, 2.2, 2.3.2, and 2.3.4). Moreover, immunization with pCHA5 in mice conferred complete (clades 1 and 2.2) or significant (clade 2.1) protection from H5N1 virus challenges. We conclude that this vaccine, based on a consensus HA, could induce broad protection against divergent H5N1 influenza viruses and thus warrants further study.
引用
收藏
页码:13538 / 13543
页数:6
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