Antibody prophylaxis and therapy against Nipah virus infection in hamsters

Antibody prophylaxis and therapy against Nipah virus infection in hamsters
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DOI:
10.1128/jvi.80.4.1972-1978.2006
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发表时间:
2006-02-01
影响因子:
5.4
通讯作者:
Wild, TF
Wild, TF
中科院分区:
医学2区
文献类型:
--
作者:
Guillaume, V;Contamin, H;Wild, TF

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尼帕病毒(NiV)是副粘病毒科的一个成员,可引起人畜共患感染,其中宿主果蝠可将感染传给猪并最终传给人类。在人类中,感染导致脑炎,死亡率> 40 - 70%。我们以前已经表明,针对两种糖蛋白,G(附着蛋白)或F(融合蛋白)之一的多克隆抗体,可以保护仓鼠免受致命感染。在本研究中,我们已经开发了两种糖蛋白的单克隆抗体(MAbs),并评估了它们保护动物免受致命NiV感染的能力。我们发现,只要1.2微克的抗G单克隆抗体保护动物,而超过1.8微克的抗F单克隆抗体需要完全保护仓鼠。高水平的抗-G或抗-F单克隆抗体提供了杀菌免疫,而较低水平可以保护免受致命感染,但导致抗NiV抗体在病毒攻击后18天开始增加。使用逆转录酶PCR,NiV的存在下,在不同的器官不能观察到单抗保护的动物。当单克隆抗体感染后给予,部分保护(50%),观察到与抗G单克隆抗体时,动物接种到感染后24小时,但管理的抗F单克隆抗体保护一些动物(25至50%)接种后在感染过程中。我们的研究表明,免疫疗法可用于暴露于NiV感染的人。
Nipah virus (NiV), a member of the Paramyxoviridae family, causes a zoonotic infection in which the reservoir, the fruit bat, may pass the infection to pigs and eventually to humans. In humans, the infection leads to encephalitis with > 40 to 70% mortality. We have previously shown that polyclonal antibody directed to either one of two glycoproteins, G (attachment protein) or F (fusion protein), can protect hamsters from a lethal infection. In the present study, we have developed monoclonal antibodies (MAbs) to both glycoproteins and assessed their ability to protect animals against lethal NiV infection. We show that as little as 1.2 mu g of an anti-G MAb protected animals, whereas more than 1.8 mu g of anti-F MAb was required to completely protect the hamsters. High levels of either anti-G or anti-F MAbs gave a sterilizing immunity, whereas lower levels could protect against a fatal infection but resulted in an increase in anti-NiV antibodies starting 18 days after the viral challenge. Using reverse transcriptase PCR, the presence of NiV in the different organs could not be observed in MAb-protected animals. When the MAbs were given after infection, partial protection (50%) was observed with the anti-G MAbs when the animals were inoculated up to 24 h after infection, but administration of the anti-F MAbs protected some animals (25 to 50%) inoculated later during the infection. Our studies suggest that immunotherapy could be used for people who are exposed to NiV infections.