title: A consensus-hemagglutinin-based DNA vaccine that protects mice against divergent H5N1 influenza viruses.
abstract: 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 approximately 60%. There is great concern that a H5N1 virus would acquire the ability to spread efficiently between humans, thereby becoming a pandemic threat. An H5N1 influenza vaccine must, therefore, be an integral part of any pandemic 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 pseudotyped 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.
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei 115, Taiwan.
authors.forename: Ming-Wei
authors.initials: MW
authors.lastname: Chen
authors.forename: Ting-Jen Rachel
authors.initials: TJ
authors.lastname: Cheng
authors.forename: Yaoxing
authors.initials: Y
authors.lastname: Huang
authors.forename: Jia-Tsrong
authors.initials: JT
authors.lastname: Jan
authors.forename: Shiou-Hwa
authors.initials: SH
authors.lastname: Ma
authors.forename: Alice L
authors.initials: AL
authors.lastname: Yu
authors.forename: Chi-Huey
authors.initials: CH
authors.lastname: Wong
authors.forename: David D
authors.initials: DD
authors.lastname: Ho