Phillpotts R J
Biomedical Sciences, Dstl, Porton Down, Salisbury SP4 0JQ, UK.
Virus Res. 2006 Sep;120(1-2):107-12. doi: 10.1016/j.virusres.2006.02.003. Epub 2006 Apr 18.
The alphavirus Venezuelan equine encephalitis virus (VEEV) is highly infectious by the airborne route. It is a hazard to laboratory workers, has been developed as a biological weapon and is a potential bioterrorist agent. A suitable vaccine appears in an advanced stage of development but there remains a need for antiviral drugs, effective in prophylaxis of disease prior to or a short time after exposure to airborne virus. Using a murine model to study monoclonal antibody (MAB) a VEEV complex-specific, glycoprotein E2-binding MAB was identified, able to protect against disease induced by exposure to aerosolised VEEV from serogroups I, II and IIIA (mouse-virulent strains). There was no synergy in protection between anti-E1 and anti-E2 MAB. Assays of MAB virus neutralising activity in a homologous (mouse fibroblast) cell line suggested that neutralisation played a significant role in protection in addition to the previously reported mechanism of Fc receptor-binding [Mathews et al., 1985. J. Virol. 55, 594-600]. Development of an analogous human MAB with identical VEEV epitope specificity may be informed and monitored by reference to these properties.
甲病毒委内瑞拉马脑炎病毒(VEEV)通过空气传播具有高度传染性。它对实验室工作人员构成危害,已被开发为生物武器,并且是一种潜在的生物恐怖主义制剂。一种合适的疫苗似乎处于开发的后期阶段,但仍然需要抗病毒药物,这些药物在暴露于空气传播病毒之前或之后短时间内对预防疾病有效。使用小鼠模型研究单克隆抗体(MAB),鉴定出一种VEEV复合物特异性、糖蛋白E2结合MAB,能够预防由暴露于来自血清群I、II和IIIA(小鼠毒力株)的雾化VEEV引起的疾病。抗E1和抗E2 MAB之间在保护作用上没有协同作用。在同源(小鼠成纤维细胞)细胞系中对MAB病毒中和活性的测定表明,除了先前报道的Fc受体结合机制外,中和作用在保护中也起重要作用[Mathews等人,1985年。《病毒学杂志》55,594 - 600]。具有相同VEEV表位特异性的类似人源MAB的开发可以参考这些特性来指导和监测。