寻找非洲猪瘟疫苗面临挑战

S. Tarigan
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摘要

非洲猪瘟(ASF)一直在印度尼西亚及其邻国流行。到目前为止,根除这种疾病的唯一可靠措施是应用严格的生物安全措施和扑杀所有感染的猪。这种方法在印度尼西亚不可行,因为大多数养猪场规模小,生物安全水平不足。接种疫苗是最实际的控制措施,但目前还没有针对非洲猪瘟的疫苗。开发非洲猪瘟疫苗遇到的困难在于,非洲猪瘟病毒非常复杂,具有使宿主免疫系统瘫痪的复杂能力。非洲猪瘟病毒感染单核细胞和巨噬细胞,导致细胞丧失免疫应答功能,进一步使疫苗开发复杂化。灭活疫苗,即使是那些含有病毒的完整结构蛋白和非结构蛋白,并为体液和细胞免疫反应添加了强效佐剂的灭活疫苗,实际上也无法诱导保护性免疫。含有重组病毒蛋白的亚单位疫苗也已开发出来,但没有一种疫苗能够提供令人满意的保护,即使疫苗显示出中和抗体。由天然低毒力病毒株或在细胞培养中反复衰减制备的活疫苗比无活性疫苗或亚单位疫苗提供更令人满意的保护性免疫。然而,它们在野外的使用造成了严重的副作用,因为突变体仍然有残留的毒力。通过删除在毒力中起作用的基因来制备活疫苗是最有希望的方法。已经确定了几种不再具有毒性但能够诱导保护性免疫的突变体;然而,在这种疫苗商业化之前,仍需要进行漫长的安全性测试。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Challenging efforts to find African Swine Fever vaccine
African swine fever (ASF) has been endemic in Indonesia and neighbouring countries. So far, the only reliable measure to eradicate the disease has been the application of strict biosecurity and culling of all infected pigs. This method is not feasible in Indonesia because most pig farms are small with a deficient level of biosecurity. Vaccination would be the most practical control measure, but no vaccine has been available for ASF. The difficulties encountered in developing the ASF vaccine lie in the fact that the ASF virus is very complex, with a sophisticated ability to paralyze the host immune system. ASF virus infects monocytes and macrophages, causing the cells to lose their functions to mount immune responses, further complicating vaccine development. Killed vaccines, even those containing complete structural and non-structural proteins of the virus and fortified with potent adjuvants for both humoral and cellular immune responses, were practically incapable of inducing protective immunity. Subunit vaccines containing recombinant viral proteins have also been developed, but none have provided satisfactory protection even though the vaccine indicates neutralizing antibodies. Live vaccines prepared from naturally low virulent viral strains or by repeated attenuation in cell cultures provided more satisfactory protective immunities than the inactive or subunit vaccines. However, their use in the field had caused severe side effects because the mutant still had residual virulence. Live vaccines prepared by deleting genes that play a role in virulence have been the most promising approach. Several mutants that were no longer virulent but capable of inducing protective immunity have been identified; however, lengthy safety testing is still needed before this vaccine is commercially available.
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