A Consensus-Hemagglutinin-Based DNA Vaccine that Protects Mice Against Divergent H5N1 Influenza Viruses
Resource
Proceedings of the National Academy of Science, 105(36), 13538-13543
Journal
Proceedings of the National Academy of Sciences
Pages
13538-13543
Date Issued
2008
Date
2008
Author(s)
Chen, Ming-Wei
Cheng, Ting-Jen Rachel
Huang, Yaoxing
Jan, Jia-Tsrong
Ma, Shiou-Hwa
Yu, Alice L.
Wong, Chi-Huey
Ho, David D.
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.
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