title: Immunization with a hemagglutinin-derived synthetic peptide formulated with a CpG-DNA-liposome complex induced protection against lethal influenza virus infection in mice.
abstract: Whole-virus vaccines, including inactivated or live-attenuated influenza vaccines, have been conventionally developed and supported as a prophylaxis. These currently available virus-based influenza vaccines are widely used in the clinic, but the vaccine production takes a long time and a huge number of embryonated chicken eggs. To overcome the imperfection of egg-based influenza vaccines, epitope-based peptide vaccines have been studied as an alternative approach. Here, we formulated an efficacious peptide vaccine without carriers using phosphodiester CpG-DNA and a special liposome complex. Potential epitope peptides predicted from the hemagglutinin (HA) protein of the H5N1 A/Viet Nam/1203/2004 strain (NCBI database, AAW80717) were used to immunize mice along with phosphodiester CpG-DNA co-encapsulated in a phosphatidyl-β-oleoyl-γ-palmitoyl ethanolamine (DOPE):cholesterol hemisuccinate (CHEMS) complex (Lipoplex(O)) without carriers. We identified a B cell epitope peptide (hH5N1 HA233 epitope, 14 amino acids) that can potently induce epitope-specific antibodies. Furthermore, immunization with a complex of the B cell epitope and Lipoplex(O) completely protects mice challenged with a lethal dose of recombinant H5N1 virus. These results suggest that our improved peptide vaccine technology can be promptly applied to vaccine development against pandemic influenza. Furthermore our results suggest that potent epitopes, which cannot be easily found using proteins or a virus as an antigen, can be screened when we use a complex of peptide epitopes and Lipoplex(O).
authors.affiliation: Center for Medical Science Research, College of Medicine, Hallym University, Gangwon-do, Republic of Korea.
authors.forename: Jae Won
authors.initials: JW
authors.lastname: Rhee
authors.forename: Dongbum
authors.initials: D
authors.lastname: Kim
authors.forename: Byung Kwon
authors.initials: BK
authors.lastname: Park
authors.forename: Sanghoon
authors.initials: S
authors.lastname: Kwon
authors.forename: Sunhee
authors.initials: S
authors.lastname: Cho
authors.forename: Ilseob
authors.initials: I
authors.lastname: Lee
authors.forename: Man-Seong
authors.initials: MS
authors.lastname: Park
authors.forename: Jae-Nam
authors.initials: JN
authors.lastname: Seo
authors.forename: Yong-Sun
authors.initials: YS
authors.lastname: Kim
authors.forename: Hong Seok
authors.initials: HS
authors.lastname: Choi
authors.forename: Younghee
authors.initials: Y
authors.lastname: Lee
authors.forename: Hyung-Joo
authors.initials: HJ
authors.lastname: Kwon
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology*; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology; D007252:Influenza Vaccines / Q000627:therapeutic use*; D008081:Liposomes; D051379:Mice; D008807:Mice, Inbred BALB C; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D009976:Orthomyxoviridae Infections / Q000517:prevention & control*; D017434:Protein Structure, Tertiary
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D008081:Liposomes; D009838:Oligodeoxyribonucleotides; C483468:hemagglutinin, human influenza A virus