State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
Virol J. 2010 Jan 18;7:9. doi: 10.1186/1743-422X-7-9.
A growing concern has raised regarding the pandemic potential of the highly pathogenic avian influenza (HPAI) H5N1 viruses. Consequently, there is an urgent need to develop an effective and safe vaccine against the divergent H5N1 influenza viruses. In the present study, we designed a tetra-branched multiple antigenic peptide (MAP)-based vaccine, designated M2e-MAP, which contains the sequence overlapping the highly conserved extracellular domain of matrix protein 2 (M2e) of a HPAI H5N1 virus, and investigated its immune responses and cross-protection against different clades of H5N1 viruses.
Our results showed that M2e-MAP vaccine induced strong M2e-specific IgG antibody responses following 3-dose immunization of mice with M2e-MAP in the presence of Freunds' or aluminium (alum) adjuvant. M2e-MAP vaccination limited viral replication and attenuated histopathological damage in the challenged mouse lungs. The M2e-MAP-based vaccine protected immunized mice against both clade1: VN/1194 and clade2.3.4: SZ/406H H5N1 virus challenge, being able to counteract weight lost and elevate survival rate following lethal challenge of H5N1 viruses.
These results suggest that M2e-MAP presenting M2e of H5N1 virus has a great potential to be developed into an effective subunit vaccine for the prevention of infection by a broad spectrum of HPAI H5N1 viruses.
高致病性禽流感(HPAI)H5N1 病毒的大流行潜力引起了人们越来越多的关注。因此,迫切需要开发针对这种具有不同特征的 H5N1 流感病毒的有效和安全疫苗。在本研究中,我们设计了一种基于四分支多抗原肽(MAP)的疫苗,命名为 M2e-MAP,它包含高度保守的 HPAI H5N1 病毒基质蛋白 2(M2)的细胞外结构域重叠序列,并研究了其针对不同 H5N1 病毒谱系的免疫反应和交叉保护作用。
我们的结果表明,在 Freunds 或铝(alum)佐剂存在的情况下,用 M2e-MAP 对小鼠进行 3 次免疫接种后,M2e-MAP 疫苗可诱导强烈的 M2e 特异性 IgG 抗体反应。M2e-MAP 疫苗接种可限制病毒复制并减轻攻毒后小鼠肺部的组织病理学损伤。基于 M2e-MAP 的疫苗可保护免疫小鼠免受 clade1:VN/1194 和 clade2.3.4:SZ/406H H5N1 病毒的攻击,能够对抗 H5N1 病毒致死性攻击导致的体重减轻和提高存活率。
这些结果表明,M2e-MAP 呈递 H5N1 病毒的 M2e 具有很大的潜力,可以开发成为预防广泛的 HPAI H5N1 病毒感染的有效亚单位疫苗。