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

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 105; no. 36; pp. 13538 - 13543
• Main Authors: Chen, Ming-Wei, Cheng, Ting-Jen Rachel, Huang, Yaoxing, Jan, Jia-Tsrong, Ma, Shiou-Hwa, Yu, Alice L, Wong, Chi-Huey, Ho, David D
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 09.09.2008; National Acad Sciences
• Subjects: Animals; Antibodies; Antibodies, Viral - blood; Antibodies, Viral - immunology; Biological Sciences; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - secretion; Cell Line; Deoxyribonucleic acid; DNA; DNA vaccines; electroporation; Gene Expression; H5N1 subtype influenza A virus; Hemagglutinin Glycoproteins, Influenza Virus - genetics; Hemagglutinin Glycoproteins, Influenza Virus - immunology; hemagglutinins; Humans; Immune response; Immunization; Influenza; Influenza A virus; Influenza A Virus, H5N1 Subtype - immunology; Influenza vaccines; Influenza Vaccines - genetics; Influenza Vaccines - immunology; Interferon-gamma - secretion; Mice; Mice, Inbred BALB C; mortality; neutralizing antibodies; Orthomyxoviridae; pandemic; Pandemics; Phylogeny; Plasmids; Plasmids - genetics; poultry; protein synthesis; recombinant vaccines; Rodents; Titrimetry; Vaccination; Vaccines; Vaccines, DNA - genetics; Vaccines, DNA - immunology; virion; Viruses; wild birds
• ISSN: 0027-8424; 1091-6490; 1091-6490
• DOI: 10.1073/pnas.0806901105

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.