评估人流感 A（H1N1）病毒和高致病性禽流感 A（H5N1）病毒之间神经氨酸酶的抗原相关性和交叉保护免疫性。

Evaluation of the antigenic relatedness and cross-protective immunity of the neuraminidase between human influenza A (H1N1) virus and highly pathogenic avian influenza A (H5N1) virus.

机构信息

Influenza Division, National Center for Immunization and Respiratory Disease, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.

出版信息

Virology. 2014 Apr;454-455:169-75. doi: 10.1016/j.virol.2014.02.011. Epub 2014 Mar 5.

DOI:10.1016/j.virol.2014.02.011

PMID:24725943

Abstract

To determine the genetic and antigenic relatedness as well as the cross-protective immunity of human H1N1 and avian H5N1 influenza virus neuraminidase (NA), we immunized rabbits with either a baculovirus-expressed recombinant NA from A/Beijing/262/95 (BJ/262) H1N1 or A/Hong Kong/483/97 (HK/483) H5N1 virus. Cross-reactive antibody responses were evaluated by multiple serological assays and cross-protection against H5N1 virus challenge was evaluated in mice. In a neuraminidase inhibition (NI) test, the antisera exhibited substantial inhibition of NA activity of the homologous virus, but failed to inhibit the NA activity of heterologous virus. However, these antisera exhibited low levels of cross-reactivity measured by plaque size reduction, replication inhibition, single radial hemolysis, and ELISA assays. Passive immunization with HK/483 NA-specific antisera significantly reduced virus replication and disease, and afforded almost complete protection against lethal homologous virus challenge in mice. However, passive immunization with BJ/262 (H1N1) NA-specific antisera was ineffective at providing cross-protection against lethal H5N1 virus challenge and only slightly reduced weight loss. Substantial amino acid variation among the NA antigenic sites was observed between BJ/262 and HK/483 virus, which was consistent with the lack of cross-reactive NI activity by the antibody and limited cross-protective immunity in mice. These results show a strong correlation between the lack of cross-protective immunity and low structural similarities of NA from a human seasonal H1N1 virus and an avian H5N1 influenza virus.

摘要

为了确定人源 H1N1 和禽流感 H5N1 流感病毒神经氨酸酶（NA）的遗传和抗原相关性以及交叉保护免疫性，我们用表达 A/Beijing/262/95（BJ/262）H1N1 或 A/Hong Kong/483/97（HK/483）H5N1 病毒的杆状病毒表达的重组 NA 免疫兔。通过多种血清学检测评估交叉反应性抗体应答，并用小鼠评估对 H5N1 病毒攻击的交叉保护作用。在神经氨酸酶抑制（NI）试验中，抗血清对同源病毒的 NA 活性具有显著抑制作用，但不能抑制异源病毒的 NA 活性。然而，这些抗血清在通过噬菌斑大小减少、复制抑制、单放射溶血和 ELISA 检测评估的交叉反应性方面显示出低水平。用 HK/483 NA 特异性抗血清进行被动免疫显著降低了病毒复制和疾病，并使小鼠对同源致死性病毒攻击几乎完全得到保护。然而，用 BJ/262（H1N1）NA 特异性抗血清进行被动免疫不能提供对致死性 H5N1 病毒攻击的交叉保护作用，仅略微减轻体重减轻。BJ/262 和 HK/483 病毒之间在 NA 抗原位点观察到大量氨基酸变异，这与抗体缺乏交叉反应性 NI 活性以及在小鼠中有限的交叉保护免疫性一致。这些结果表明，人季节性 H1N1 病毒和禽流感 H5N1 流感病毒的 NA 之间缺乏交叉保护免疫性与结构相似性低之间存在很强的相关性。