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口蹄疫豚鼠模型中病毒中和位点对毒力和疫苗保护的生物学相关性。

The biological relevance of virus neutralisation sites for virulence and vaccine protection in the guinea pig model of foot-and-mouth disease.

作者信息

Dunn C S, Samuel A R, Pullen L A, Anderson J

机构信息

Institute for Animal Health, Pirbright Laboratory, Woking, Surrey, United Kingdom.

出版信息

Virology. 1998 Jul 20;247(1):51-61. doi: 10.1006/viro.1998.9175.

DOI:10.1006/viro.1998.9175
PMID:9683571
Abstract

Five neutralisation epitopes have been defined for the O1 Kaufbeuren strain of foot-and-mouth disease virus (FMDV) by neutralising murine monoclonal antibodies (Mabs). A mutant virus which is resistant to all these Mabs also resists neutralisation by bovine polyclonal sera, and this characteristic was exploited in the current study to investigate the biological relevance of neutralisation sites in FMDV virulence and vaccine protection. The five site neutralisation-resistant mutant was shown to be as pathogenic as wild-type virus in the guinea pig model of FMD. Guinea pigs were protected in cross-challenge studies from virulent wild-type and mutant viruses using either wild-type or mutant 146S antigen as inactivated whole virus vaccine. Furthermore, hyperimmune sera raised to either wild-type or mutant antigen offered passive protection against wild-type challenge, in spite of the serum raised against the mutant antigen having minimal neutralising activity in vitro. These results imply that virus neutralisation, at least as defined by the in vitro assay, may not play an essential role in the mechanism of immunity induced by whole inactivated FMDV vaccines.

摘要

通过中和鼠单克隆抗体(Mab),已为口蹄疫病毒(FMDV)的O1考夫博伊伦毒株确定了五个中和表位。一种对所有这些单克隆抗体均具有抗性的突变病毒,同样也能抵抗牛多克隆血清的中和作用,并且在当前研究中利用这一特性来探究FMDV毒力和疫苗保护中中和位点的生物学相关性。在口蹄疫豚鼠模型中,五个位点中和抗性突变体显示出与野生型病毒一样具有致病性。在交叉攻毒研究中,使用野生型或突变型146S抗原作为灭活全病毒疫苗,豚鼠受到了针对强毒野生型和突变型病毒的保护。此外,针对野生型或突变型抗原产生的超免疫血清,尽管针对突变型抗原产生的血清在体外具有最小的中和活性,但仍能提供针对野生型攻毒的被动保护。这些结果表明,至少按照体外试验所定义的病毒中和作用,可能在全灭活FMDV疫苗诱导的免疫机制中不发挥重要作用。

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