Production of antigenically stable enterovirus A71 virus-like particles in Pichia pastoris as a vaccine candidate.
Production of antigenically stable enterovirus A71 virus-like particles in Pichia pastoris as a vaccine candidate.
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DOI：
10.1099/jgv.0.001867
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发表时间：
2023-06
影响因子：
3.8
通讯作者：
Stonehouse, Nicola J.
中科院分区：
文献类型：
--
作者：
Kingston, Natalie J.;Snowden, Joseph S.;Martyna, Agnieszka;Shegdar, Mona;Grehan, Keith;Tedcastle, Alison;Pegg, Elaine;Fox, Helen;Macadam, Andrew J.;Martin, Javier;Hogle, James M.;Rowlands, David J.;Stonehouse, Nicola J.
肠病毒A71（EVA 71）在幼儿中引起广泛的疾病，偶尔有致命的后果。与其他小核糖核酸病毒一样，空衣壳（EC）和感染性病毒粒子都在病毒生命周期中产生。虽然最初在抗原性上与病毒体无法区分，但EC在中等温度下容易转化为扩展构象。在密切相关的脊髓灰质炎病毒中，这些构象变化导致引起保护性免疫应答所需的抗原位点的丢失。EVA 71是否如此仍有待确定，这也是本研究的主题。我们先前报道了使用连续轮的加热和通过选择耐热EVA 71基因组B2人口。在所选群体的结构蛋白编码区中发现的突变赋予病毒体和天然产生的EC增加的热稳定性。在这里，我们将这些突变引入到重组表达系统中，以在巴斯德毕赤酵母中产生稳定的病毒样颗粒（VLP）。稳定化的VLP保留天然病毒体样抗原构象，如通过与特异性抗体的反应性所确定的。结构研究表明抗原稳定化的多种潜在机制，然而，与脊髓灰质炎病毒不同，天然和扩增的EVA 71颗粒均引发能够在体外直接中和病毒的抗体。因此，抗-EVA 71中和抗体由与天然构象不典型相关的位点引发，但对天然构象特异的抗原位点是否在体内提供额外的保护性应答仍不清楚。VLP可能为疫苗生产提供更便宜和更安全的替代品，这些数据表明，VLP疫苗在诱导中和抗体方面与灭活病毒疫苗相当。
Enterovirus A71 (EVA71) causes widespread disease in young children with occasional fatal consequences. In common with other picornaviruses, both empty capsids (ECs) and infectious virions are produced during the viral lifecycle. While initially antigenically indistinguishable from virions, ECs readily convert to an expanded conformation at moderate temperatures. In the closely related poliovirus, these conformational changes result in loss of antigenic sites required to elicit protective immune responses. Whether this is true for EVA71 remains to be determined and is the subject of this investigation. We previously reported the selection of a thermally resistant EVA71 genogroup B2 population using successive rounds of heating and passage. The mutations found in the structural protein-coding region of the selected population conferred increased thermal stability to both virions and naturally produced ECs. Here, we introduced these mutations into a recombinant expression system to produce stabilized virus-like particles (VLPs) in Pichia pastoris. The stabilized VLPs retain the native virion-like antigenic conformation as determined by reactivity with a specific antibody. Structural studies suggest multiple potential mechanisms of antigenic stabilization, however, unlike poliovirus, both native and expanded EVA71 particles elicited antibodies able to directly neutralize virus in vitro. Therefore, anti-EVA71 neutralizing antibodies are elicited by sites which are not canonically associated with the native conformation, but whether antigenic sites specific to the native conformation provide additional protective responses in vivo remains unclear. VLPs are likely to provide cheaper and safer alternatives for vaccine production and these data show that VLP vaccines are comparable with inactivated virus vaccines at inducing neutralising antibodies.
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影响因子：
5.4
作者：
Adeyemi OO;Nicol C;Stonehouse NJ;Rowlands DJ
通讯作者：
Rowlands DJ
影响因子：
5.5
作者：
Chung, Yao-Chi;Ho, Mei-Shang;Hu, Yu-Chen
通讯作者：
Hu, Yu-Chen
影响因子：
8
作者：
BASAVAPPA, R;SYED, R;HOGLE, JM
通讯作者：
HOGLE, JM
影响因子：
6.4
作者：
Mulders, MN;Reimerink, JHJ;vanderAvoort, HGAM
通讯作者：
vanderAvoort, HGAM
DOI：
10.1107/s0907444909052925
发表时间：
2010-02
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Adams PD;Afonine PV;Bunkóczi G;Chen VB;Davis IW;Echols N;Headd JJ;Hung LW;Kapral GJ;Grosse-Kunstleve RW;McCoy AJ;Moriarty NW;Oeffner R;Read RJ;Richardson DC;Richardson JS;Terwilliger TC;Zwart PH
通讯作者：
Zwart PH