Polyvalent DNA vaccines expressing HA antigens of H5N1 influenza viruses with an optimized leader sequence elicit cross-protective antibody responses

• Published in: PloS one Vol. 6; no. 12; p. e28757
• Main Authors: Wang, Shixia, Hackett, Anthony, Jia, Na, Zhang, Chunhua, Zhang, Lu, Parker, Chris, Zhou, An, Li, Jun, Cao, Wu-Chun, Huang, Zuhu, Li, Yan, Lu, Shan
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 21.12.2011; Public Library of Science (PLoS)
• Subjects: Analysis; Animals; Antibodies, Viral - immunology; Antigen-antibody reactions; Antigens; Antigens, Viral - genetics; Antigens, Viral - immunology; Avian flu; Avian influenza; Biology; Cross Reactions; Deoxyribonucleic acid; Design optimization; DNA; DNA vaccines; Epidemiology; Gene Expression; Genetic research; Glycoproteins; Glycosylation; Health aspects; Hemagglutinin Glycoproteins, Influenza Virus - genetics; Hemagglutinin Glycoproteins, Influenza Virus - immunology; Hemagglutinins; Hospitals; Humans; Immunization; Infection; Infections; Infectious diseases; Influenza; Influenza A; Influenza A Virus, H5N1 Subtype - immunology; Influenza vaccines; Influenza viruses; International relations-US; Laboratories; Lectins; Medical research; Medical schools; Medicine; Mutation; Pandemics; Pathogens; Phylogeny; Protein Sorting Signals; Rabbits; Severe acute respiratory syndrome; Species Specificity; Vaccines; Vaccines, DNA - chemistry; Vaccines, DNA - genetics; Vaccines, DNA - immunology; Vaccines, DNA - metabolism; Viruses; Beijing China; United States > US; Massachusetts; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0028757

Highly pathogenic avian influenza A (HPAI) H5N1 viruses are circulating among poultry populations in parts of Asia, Africa, and the Middle East, and have caused human infections with a high mortality rate. H5 subtype hemagglutinin (HA) has evolved into phylogenetically distinct clades and subclades based on viruses isolated from various avian species. Since 1997, humans have been infected by HPAI H5N1 viruses from several clades. It is, therefore, important to develop strategies to produce protective antibody responses against H5N1 viruses from multiple clades or antigenic groups. In the current study, we optimized the signal peptide design of DNA vaccines expressing HA antigens from H5N1 viruses. Cross reactivity analysis using sera from immunized rabbits showed that antibody responses elicited by a polyvalent formulation, including HA antigens from different clades, was able to elicit broad protective antibody responses against multiple key representative H5N1 viruses across different clades. Data presented in this report support the development of a polyvalent DNA vaccine strategy against the threat of a potential H5N1 influenza pandemic.