Unit of Antiviral Immunity and Genetic Therapy, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.
J Infect Dis. 2014 Mar 1;209(5):676-85. doi: 10.1093/infdis/jit414. Epub 2013 Aug 2.
Since 1996, highly pathogenic avian influenza (HPAI) H5N1 virus has presented a persistent threat to public health. Its high degree of genetic diversity also poses enormous challenges in developing effective vaccines. To search for vaccine regimens that could elicit broadly neutralizing antibody responses against diverse HPAI H5N1 strains, in the present study we tested H5 hemagglutinin (HA) from an A/Thailand/1(KAN)-1/2004 strain in a heterologous prime-boost vaccination. We demonstrated that priming mice with DNA and boosting with virus-like particle induced antibody responses that cross-neutralize all reported clades and subclades of HPAI H5N1 viruses and protect mice from high lethal dose HPAI H5N1 challenge in both active and passive immunizations. Unexpectedly, cross-divergent H5 neutralizing antibodies are directed to the HA head and block both attachment and postattachment of virus entry. Thus, we conclude that as a promising pan-H5 vaccine candidate this prime-boost regimen could be further developed in ferrets and in humans.
自 1996 年以来，高致病性禽流感（HPAI）H5N1 病毒一直对公共卫生构成持续威胁。其高度的遗传多样性也给开发有效疫苗带来了巨大挑战。为了寻找能够引发针对不同高致病性禽流感 H5N1 毒株的广泛中和抗体反应的疫苗方案，在本研究中，我们在异源初免-加强免疫中测试了来自 A/泰国/1(KAN)-1/2004 株的 H5 血凝素（HA）。我们证明，用 DNA 对小鼠进行初免并用病毒样颗粒进行加强免疫，可诱导交叉中和所有报告的高致病性禽流感 H5N1 病毒的所有谱系和亚谱系的抗体反应，并在主动和被动免疫中保护小鼠免受高致死剂量的高致病性禽流感 H5N1 挑战。出乎意料的是，交叉分化的 H5 中和抗体针对 HA 头部，阻止病毒进入的附着和附着后阶段。因此，我们得出结论，作为一种有前途的泛 H5 疫苗候选物，这种初免-加强免疫方案可以在雪貂和人类中进一步开发。
