College of Medicine and Medical Research Institute, Chungbuk National University, Cheongju, 361-763, Republic of Korea.
J Microbiol. 2012 Jun;50(3):478-88. doi: 10.1007/s12275-012-1573-z. Epub 2012 Jun 30.
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.
高致病性禽流感 (HPAI) H5N1 病毒引发下一次大流行的威胁仍然是一个主要关注点。在这项研究中，我们评估了由 Green Cross 公司制备的灭活全病毒 H5N1 大流行前疫苗（MG1109）的免疫原性和疗效，该疫苗包含 A/Vietnam/1194/04 病毒的血凝素 (HA) 和神经氨酸酶 (NA) 基因，作为 A/Puerto Rico/8/34（RgVietNam/04xPR8/34）的骨架。MG1109 疫苗（2 剂）在小鼠和雪貂中的给药方式，以剂量依赖性方式针对同源（RgVietNam/04xPR8/34）和各种异源 H5N1 株（RgKor/W149/06xPR8/34、RgCambodia/04xPR8/34、RgGuangxi/05xPR8/34），包括异亚型 H5N2（A/Aquatic bird/orea/W81/05）病毒，引起高 HI 和 SN 滴度。然而，针对异亚型 H9N2（A/Ck/Korea/H0802/08）和 H1N1（PR/8/34）病毒没有观察到有效的交叉反应性。用 1.9 μg HA/剂量的 MG1109 免疫的小鼠完全免受同源野生型 HPAI H5N1 A/EM/Korea/W149/06（clade 2.2）和鼠适应的 H5N2 病毒的致死性挑战。此外，给予至少 3.8 μg HA/剂量的雪貂有效地抑制了上呼吸道和肺部的病毒生长。接种疫苗的小鼠和雪貂还表现出临床疾病迹象的减轻和病毒向其他器官的传播有限。因此，该疫苗在小鼠和雪貂模型中提供了免疫应答，甚至在面临异源 HPAI H5N1 和 H5N2 病毒的挑战时也是如此。由于潜在引发下一次爆发的高致病性禽流感 H5N1 病毒的特定菌株尚不清楚，因此针对各种 H5 株提供交叉保护的大流行前疫苗制备可能是未来选择有前途的候选疫苗的一种有用方法。
