title: Investigation of the biological indicator for vaccine efficacy against highly pathogenic avian influenza (HPAI) H5N1 virus challenge in mice and ferrets.
abstract: To investigate the biological indicator for vaccine efficacy against HPAI H5N1 virus challenge of varying clades, two inactivated whole-virus H5N1 vaccines containing the hemagglutinin (HA) and neuraminidase (NA) genes of either clade 2.2 A/EM/Korea/W149/06 (RgKoreaW149/06 x PR8) or clade 2.5 A/Ck/Korea/ES/03 (RgKoreaES223N/03XPR8) virus in the background of A/PR/8/34 (H1N1) were generated by reverse genetics. Administration of the vaccines (2-dose 1.77, 3.5, 7.5 or 15microg of HA) elicited high HI titers in a dose-dependent manner. Mice immunized with RgKoreaW149/06 x PR8 were completely protected from challenge against wild-type A/EM/Korea/W149/06 without clinical signs of infection. RgKoreaES223N/03XPR8 could not protect mice at 1.77microg while all immunized ferrets were completely protected. Two-dose (7.5microg) vaccinated mice (HI titer > or =320) and triple dose (7.5 microg) vaccinated ferrets with RgKoreaES223N/03xPR8 (HI titer > or =640) protected vaccine recipients from mortality, inhibited nasal virus shedding and limited influenza virus tropism. Thus, these vaccines provided cross-protectivity in both models. More importantly, these results collectively suggested a positive correlation between vaccine-induced HI titers and inhibition of virus shedding including block of viral proliferation in major organs against a heterologous HPAI H5N1 virus. Although developing technologies or methods that will enable the reduction of administration dose/frequency remains to be resolved, our study demonstrated a considerable biological marker (> or =640 HI titer) for full protection of the vaccinated hosts that could provide a preliminary basis for the assessment of complete immunization.
authors.affiliation: College of Medicine and Medical Research Institute, Chungbuk National University, Cheongju 361-763, Republic of Korea.
authors.forename: Min-Suk
authors.initials: MS
authors.lastname: Song
authors.forename: Taek-Kyu
authors.initials: TK
authors.lastname: Oh
authors.forename: Philippe Noriel Q
authors.initials: PN
authors.lastname: Pascua
authors.forename: Ho-Jin
authors.initials: HJ
authors.lastname: Moon
authors.forename: Jun Han
authors.initials: JH
authors.lastname: Lee
authors.forename: Yun Hee
authors.initials: YH
authors.lastname: Baek
authors.forename: Kyu-Jin
authors.initials: KJ
authors.lastname: Woo
authors.forename: Yeup
authors.initials: Y
authors.lastname: Yoon
authors.forename: Moon-Hee
authors.initials: MH
authors.lastname: Sung
authors.forename: Haryoung
authors.initials: H
authors.lastname: Poo
authors.forename: Chul-Joong
authors.initials: CJ
authors.lastname: Kim
authors.forename: Young Ki
authors.initials: YK
authors.lastname: Choi
mesh_terms: D000818:Animals; D015415:Biomarkers; D005289:Ferrets; D006385:Hemagglutination Inhibition Tests; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology* / Q000472:pathogenicity; D007252:Influenza Vaccines / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000517:prevention & control; D014611:Vaccination
chemical_list: D015415:Biomarkers; D007252:Influenza Vaccines