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Custom-engineered chimeric foot-and-mouth disease vaccine elicits protective immune responses in pigs

机译:定制工程嵌合口蹄疫疫苗引发猪的保护性免疫反应

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摘要

Chimeric foot-and-mouth disease viruses (FMDV) of which the antigenic properties can be readily manipulated is a potentially powerful approach in the control of foot-and-mouth disease (FMD) in sub-Saharan Africa. FMD vaccine application is complicated by the extensive variability of the South African Territories (SAT) type viruses, which exist as distinct genetic and antigenic variants in different geographical regions. A cross-serotype chimeric virus, vKNP/SAT2, was engineered by replacing the external capsid-encoding region (1B-1D/2A) of an infectious cDNA clone of the SAT2 vaccine strain, ZIM/7/83, with that of SAT1 virus KNP/196/91. The vKNP/SAT2 virus exhibited comparable infection kinetics, virion stability and antigenic profiles to the KNP/196/91 parental virus, thus indicating that the functions provided by the capsid can be readily exchanged between serotypes. As these qualities are necessary for vaccine manufacturing, high titres of stable chimeric virus were obtained. Chemically inactivated vaccines, formulated as double-oil-in-water emulsions, were produced from intact 146S virion particles of both the chimeric and parental viruses. Inoculation of guinea pigs with the respective vaccines induced similar antibody responses. In order to show compliance with commercial vaccine requirements, the vaccines were evaluated in a full potency test. Pigs vaccinated with the chimeric vaccine produced neutralizing antibodies and showed protection against homologous FMDV challenge, albeit not to the same extent as for the vaccine prepared from the parental virus. These results provide support that chimeric vaccines containing the external capsid of field isolates can be successfully produced and that they induce protective immune responses in FMD host species.
机译:易于控制其抗原特性的嵌合型口蹄疫病毒(FMDV)是控制撒哈拉以南非洲地区口蹄疫(FMD)的潜在强大方法。口蹄疫疫苗的应用由于南非领土(SAT)型病毒的广泛变异而变得复杂,该病毒作为不同地理区域的不同遗传和抗原变体而存在。通过用SAT1病毒替代SAT2疫苗株ZIM / 7/83的传染性cDNA克隆的外部衣壳编码区(1B-1D / 2A),设计出了一种跨血清型嵌合病毒vKNP / SAT2。 KNP / 196/91。 vKNP / SAT2病毒表现出与KNP / 196/91亲本病毒相当的感染动力学,病毒体稳定性和抗原特性,因此表明衣壳提供的功能可以在血清型之间轻松交换。由于这些质量对于疫苗生产是必需的,因此获得了高滴度的稳定嵌合病毒。化学灭活疫苗配制成水包油双乳剂,是由嵌合和亲本病毒的完整146S病毒粒子制成的。用相应的疫苗接种豚鼠可引起相似的抗体反应。为了显示符合商业疫苗要求,在全面效能测试中对疫苗进行了评估。接种嵌合疫苗的猪产生中和抗体,并显示出针对同源FMDV攻击的保护作用,尽管程度与从亲本病毒制备的疫苗不同。这些结果提供了支持,可以成功地生产出包含现场分离株的外部衣壳的嵌合疫苗,并且它们在FMD宿主物种中诱导保护性免疫应答。

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