title: Evaluation of the efficacy of a pre-pandemic H5N1 vaccine (MG1109) in mouse and ferret models.
abstract: The threat of a highly pathogenic avian influenza (HPAI) H5N1 virus causing the next pandemic remains a major concern. In this study, we evaluated the immunogenicity and efficacy of an inactivated whole-virus H5N1 pre-pandemic vaccine (MG1109) formulated by Green Cross Co., Ltd containing the hemagglutinin (HA) and neuraminidase (NA) genes of the clade 1 A/Vietnam/1194/04 virus in the backbone of A/Puerto Rico/8/34 (RgVietNam/04xPR8/34). Administration of the MG1109 vaccine (2-doses) in mice and ferrets elicited high HI and SN titers in a dose-dependent manner against the homologous (RgVietNam/04xPR8/34) and various heterologous H5N1 strains, (RgKor/W149/06xPR8/34, RgCambodia/04xPR8/34, RgGuangxi/05xPR8/34), including a heterosubtypic H5N2 (A/Aquatic bird/orea/W81/05) virus. However, efficient cross-reactivity was not observed against heterosubtypic H9N2 (A/Ck/Korea/H0802/08) and H1N1 (PR/8/34) viruses. Mice immunized with 1.9 μg HA/dose of MG1109 were completely protected from lethal challenge with heterologous wild-type HPAI H5N1 A/EM/Korea/W149/06 (clade 2.2) and mouse-adapted H5N2 viruses. Furthermore, ferrets administered at least 3.8 μg HA/dose efficiently suppressed virus growth in the upper respiratory tract and lungs. Vaccinated mice and ferrets also demonstrated attenuation of clinical disease signs and limited virus spread to other organs. Thus, this vaccine provided immunogenic responses in mouse and ferret models even against challenge with heterologous HPAI H5N1 and H5N2 viruses. Since the specific strain of HPAI H5N1 virus that would potentially cause the next outbreak is unknown, pre-pandemic vaccine preparation that could provide cross-protection against various H5 strains could be a useful approach in the selection of promising candidate vaccines in the future.
authors: College of Medicine and Medical Research Institute, Chungbuk National University, Cheongju, 361-763, Republic of Korea.
authors: Min-Suk
authors: MS
authors: Song
authors: Ho-Jin
authors: HJ
authors: Moon
authors: Hyeok-Il
authors: HI
authors: Kwon
authors: Philippe Noriel Q
authors: PN
authors: Pascua
authors: Jun Han
authors: JH
authors: Lee
authors: Yun Hee
authors: YH
authors: Baek
authors: Gyu-Jin
authors: GJ
authors: Woo
authors: Kyu-Jin
authors: KJ
authors: Woo
authors: Juhee
authors: J
authors: Choi
authors: Sangho
authors: S
authors: Lee
authors: Hyunseung
authors: H
authors: Yoo
authors: Ingyeong
authors: I
authors: Oh
authors: Yeup
authors: Y
authors: Yoon
authors: Jong-Bok
authors: JB
authors: Rho
authors: Moon-Hee
authors: MH
authors: Sung
authors: Seung-Pyo
authors: SP
authors: Hong
authors: Chul-Joong
authors: CJ
authors: Kim
authors: Young Ki
authors: YK
authors: Choi
mesh_terms: D054366:Agouti Signaling Protein; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D003429:Cross Reactions; D004195:Disease Models, Animal; D005289:Ferrets; D006385:Hemagglutination Inhibition Tests; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics / Q000276:immunology; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D051379:Mice; D009439:Neuraminidase / Q000235:genetics / Q000276:immunology; D009500:Neutralization Tests; D009976:Orthomyxoviridae Infections / Q000517:prevention & control*; D056910:Republic of Korea; D016019:Survival Analysis; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology
chemical_list: D054366:Agouti Signaling Protein; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D014764:Viral Proteins; C515183:a protein, mouse; C487630:NA protein, influenza A virus; D009439:Neuraminidase