An anthrax subunit vaccine candidate based on protective regions of Bacillus anthracis protective antigen and lethal factor.
An anthrax subunit vaccine candidate based on protective regions of Bacillus anthracis protective antigen and lethal factor.
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DOI：
10.1016/j.vaccine.2010.07.075
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发表时间：
2010-09-24
期刊：
影响因子：
5.5
通讯作者：
Pasetti, Marcela F.
中科院分区：
文献类型：
--
作者：
Baillie, Les W.;Huwar, Theresa B.;Moore, Stephen;Mellado-Sanchez, Gabriela;Rodriguez, Liliana;Neeson, Brendan N.;Flick-Smith, Helen C.;Jenner, Dominic C.;Atkins, Helen S.;Ingram, Rebecca J.;Altmann, Danny M.;Nataro, James P.;Pasetti, Marcela F.
研究证实了炭疽杆菌保护性抗原（PA）在美国和英国人类炭疽疫苗中的关键作用。然而，鉴于毒素的三方性质，其他成分，包括致死因子（LF），也可能有助于保护。我们研究了抗体和T细胞的反应PA和LF在人类志愿者与英国炭疽疫苗（AVP）免疫。当单独或与PA一起给予时，评估单个LF结构域在小鼠中的免疫原性。基于所获得的结果，评估了包含LF的D1和PA的宿主细胞结合结构域（D4）的新型融合蛋白的保护功效。小鼠保护研究表明，全长LF和LF的D1赋予完全保护免受致死性腹膜内攻击与B。炭疽病STI孢子。随后对LFD 1-PAD 4融合蛋白的研究显示了类似的保护水平。LF在人体中具有免疫原性，可能有助于AVP刺激的保护作用。包含来自LF和PA的保护性区域的单一疫苗将简化生产并赋予比单独使用PA所见的更广谱的保护。
Studies have confirmed the key role of Bacillus anthracis protective antigen (PA) in the US and UK human anthrax vaccines. However, given the tripartite nature of the toxin, other components, including lethal factor (LF), are also likely to contribute to protection. We examined the antibody and T cell responses to PA and LF in human volunteers immunized with the UK anthrax vaccine (AVP). Individual LF domains were assessed for immunogenicity in mice when given alone or with PA. Based on the results obtained, a novel fusion protein comprising D1 of LF and the host cell-binding domain of PA (D4) was assessed for protective efficacy. Murine protection studies demonstrated that both full-length LF and D1 of LF conferred complete protection against a lethal intraperitoneal challenge with B. anthracis STI spores. Subsequent studies with the LFD1-PAD4 fusion protein showed a similar level of protection. LF is immunogenic in humans and is likely to contribute to the protection stimulated by AVP. A single vaccine comprising protective regions from LF and PA would simplify production and confer a broader spectrum of protection than that seen with PA alone.
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影响因子：
5.5
作者：
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