A consensus?hemagglutinin-based DNA vaccine that protects mice against divergent H5N1 influenza viruses
Ming-Wei Chen*,?, Ting-Jen Rachel Cheng*, Yaoxing Huang?, Jia-Tsrong Jan*, Shiou-Hwa Ma*, Alice L. Yu*, Chi-Huey Wong*,?, and David D. Ho*,?,?
*Genomics Research Center, Academia Sinica, Taipei 115, Taiwan;
?Aaron Diamond AIDS Research Center, The Rockefeller University, New York, NY 10016; and
?Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei 112, Taiwan
Contributed by Chi-Huey Wong, July 16, 2008 (sent for review June 12, 2008)
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 ≈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.
http://intl.pnas.org/content/early/2008/09/02/0806901105.abstract
Ming-Wei Chen*,?, Ting-Jen Rachel Cheng*, Yaoxing Huang?, Jia-Tsrong Jan*, Shiou-Hwa Ma*, Alice L. Yu*, Chi-Huey Wong*,?, and David D. Ho*,?,?
*Genomics Research Center, Academia Sinica, Taipei 115, Taiwan;
?Aaron Diamond AIDS Research Center, The Rockefeller University, New York, NY 10016; and
?Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei 112, Taiwan
Contributed by Chi-Huey Wong, July 16, 2008 (sent for review June 12, 2008)
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 ≈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.
http://intl.pnas.org/content/early/2008/09/02/0806901105.abstract