Disparity between levels of in vitro neutralization of vaccinia virus by antibody to the A27 protein and protection of mice against intranasal challenge
Disparity between levels of in vitro neutralization of vaccinia virus by antibody to the A27 protein and protection of mice against intranasal challenge
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DOI：
10.1128/jvi.00568-08
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发表时间：
2008-08-01
影响因子：
5.4
通讯作者：
Moss, Bernard
中科院分区：
文献类型：
--
作者：
Fogg, Christiana N.;Arnerico, Jeffrey L.;Moss, Bernard
用重组蛋白免疫可以提供一种比活牛痘病毒更安全的替代物，用于预防痘病毒感染。尽管抗体可以保护牛痘病毒感染，但其机制尚不清楚，并且免疫原的选择令人生畏，因为存在数十种表面蛋白和两种称为成熟病毒体（MV）和包膜病毒体（EV）的感染形式。我们以前的研究表明，用可溶性形式的EV膜蛋白A33和B5以及MV膜蛋白L1免疫的小鼠或用这些蛋白的抗体被动免疫的小鼠在用牛痘病毒的鼻内攻击中存活。本研究比较了MV蛋白A27（其在病毒附着于细胞表面的糖胺聚糖中具有作用）与L1的免疫原性和保护作用。尽管小鼠在用A27或L1免疫后产生了相似水平的中和抗体，但A27免疫的小鼠在用牛痘病毒鼻内攻击后表现出更严重的疾病。此外，用A27和A33免疫的小鼠不如接受L1和A33的小鼠受到良好的保护。多克隆兔抗-A27和抗-L1 IgG具有等效的W-中和活性，当通过预防感染人或小鼠细胞或缺乏糖胺聚糖的细胞或通过在病毒吸附之前或之后添加抗体来测量时。然而，与L1抗体相比，被动给予A27抗体的保护性较差。这些研究提出了关于痘病毒病抗体保护基础的问题，并强调了动物模型对候选疫苗早期评价的重要性。
Immunization with recombinant proteins may provide a safer alternative to live vaccinia virus for prophylaxis of poxvirus infections. Although antibody protects against vaccinia virus infection, the mechanism is not understood and the selection of immunogens is daunting as there are dozens of surface proteins and two infectious forms known as the mature virion (MV) and the enveloped virion (EV). Our previous studies showed that mice immunized with soluble forms of EV membrane proteins A33 and B5 and MV membrane protein L1 or passively immunized with antibodies to these proteins survived an intranasal challenge with vaccinia virus. The present study compared MV protein A27, which has a role in virus attachment to glycosaminoglycans on the cell surface, to L1 with respect to immunogenicity and protection. Although mice developed similar levels of neutralizing antibody after immunizations with A27 or L1, A27-immunized mice exhibited more severe disease upon an intranasal challenge with vaccinia virus. In addition, mice immunized with A27 and A33 were not as well protected as mice receiving L1 and A33. Polyclonal rabbit anti-A27 and anti-L1 IgG had equivalent W-neutralizing activities when measured by the prevention of infection of human or mouse cells or cells deficient in glycosaminoglycans or by adding antibody prior to or after virus adsorption. Nevertheless, the passive administration of antibody to A27 was poorly protective compared to the antibody to L1. These studies raise questions regarding the basis for antibody protection against poxvirus disease and highlight the importance of animal models for the early evaluation of vaccine candidates.