Assessment of the Protective Effect of Imvamune and Acam2000 Vaccines against Aerosolized Monkeypox Virus in Cynomolgus Macaques

Assessment of the Protective Effect of Imvamune and Acam2000 Vaccines against Aerosolized Monkeypox Virus in Cynomolgus Macaques
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DOI:
10.1128/jvi.03481-12
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发表时间:
2013-07-01
影响因子:
5.4
通讯作者:
Vipond, Julia
Vipond, Julia
中科院分区:
医学2区
文献类型:
--
作者:
Hatch, Graham J.;Graham, Victoria A.;Vipond, Julia

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为了支持一种新的更安全的疫苗的许可证,以保护人们免受天花,在食蟹猴中的猴痘感染模型,模拟人类天花,用于评估两种疫苗,Acam 2000和Imvamune,对疾病的保护。用Imvamune单次免疫接种的动物不能完全免受严重和/或致死性感染,而接受Imvamune初免和加强或用Acam 2000单次免疫接种的动物则得到完全保护。评估了其他参数,包括临床观察结果、X线片、血液、咽拭子和选定组织中的病毒载量、牛痘病毒特异性抗体应答、免疫表型、细胞外细胞因子水平和组织病理学。猴痘病毒攻毒前Acam 2000单次免疫(132 U/ml)和Imvamune初免-加强免疫(69 U/ml)的动物中和抗体水平无显著差异(P>0.05)。攻毒后,有证据表明,免疫初免-加强免疫Imvamune组6只动物中有2只动物的喉咙中有病毒排泄,而Acam 2000组中未证实有活病毒排泄。在食蟹猴中对不同人天花疫苗的评价有助于提供在缺乏人攻毒研究的情况下最佳疫苗策略的信息。
To support the licensure of a new and safer vaccine to protect people against smallpox, a monkeypox model of infection in cynomolgus macaques, which simulates smallpox in humans, was used to evaluate two vaccines, Acam2000 and Imvamune, for protection against disease. Animals vaccinated with a single immunization of Imvamune were not protected completely from severe and/or lethal infection, whereas those receiving either a prime and boost of Imvamune or a single immunization with Acam2000 were protected completely. Additional parameters, including clinical observations, radiographs, viral load in blood, throat swabs, and selected tissues, vaccinia virus-specific antibody responses, immunophenotyping, extracellular cytokine levels, and histopathology were assessed. There was no significant difference (P>0.05) between the levels of neutralizing antibody in animals vaccinated with a single immunization of Acam2000 (132 U/ml) and the prime-boost Imvamune regime (69 U/ml) prior to challenge with monkeypox virus. After challenge, there was evidence of viral excretion from the throats of 2 of 6 animals in the prime-boost Imvamune group, whereas there was no confirmation of excreted live virus in the Acam2000 group. This evaluation of different human smallpox vaccines in cynomolgus macaques helps to provide information about optimal vaccine strategies in the absence of human challenge studies.