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Sindbis virus replicase-based dna vaccine construct encoding fmdv-specific multivalent epitope gene: Studies on its immune responses in guinea pigs

机译:基于sindbis病毒复制酶的dna疫苗构建体,编码fmdv特异性多价表位基因:在豚鼠中的免疫应答研究

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Foot-and-mouth disease (FMD) is still a perennial global menace affecting livestock health and production. It is imperative to figure out new ways to curb this disease. In this study, a sindbis virus replicase-based DNA vaccine, pSinCMV-Vac-MEG990, encoding a multivalent epitope gene (representing tandemly linked VP1 C-terminal halves of three foot-and-mouth disease virus (FMDV) serotypes) was constructed. In vitro transfection studies in BHK-21 cells revealed that the construct was able to express FMDV-specific antigen but does not overproduce the antigen. Immunization of guinea pigs with the construct at dose rate of 10, 5, 2 and 1μg per animal through intramuscular route showed significant neutralizing antibody induction at all doses against all serotype tested as compared to non-immunized controls. On viral challenge of guinea pigs 4week post-immunization with 1000 GPID 50 of FMDV serotype A, it was observed that the immunization not only delayed the appearance and reduced the severity of FMD lesions significantly (P0.05) but also provided complete protection in several guinea pigs. In fact, two of six and one of six guinea pigs were completely protected in 10 and 5μg immunized groups, respectively. These results suggest that the development of the replicase-based DNA vaccine may provide a promising approach as an alternative vaccine strategy for controlling FMD.
机译:口蹄疫仍然是影响牲畜健康和生产的全球威胁。必须找到遏制这种疾病的新方法。在这项研究中,构建了一种基于sindbis病毒复制酶的DNA疫苗pSinCMV-Vac-MEG990,该疫苗编码一个多价表位基因(代表三只口蹄疫病毒(FMDV)血清型的串联连接的VP1 C末端一半)。在BHK-21细胞中进行的体外转染研究表明,该构建体能够表达FMDV特异性抗原,但不会过度产生该抗原。与未免疫的对照相比,以每只动物通过肌肉内途径以10、5、2和1μg的剂量率对构建体进行的豚鼠免疫接种显示在所有剂量下针对所有测试的血清型的中和性抗体诱导显着。用1000 GPID 50的FMDV血清型A免疫豚鼠后4周进行病毒攻击,观察到该免疫不仅显着延迟了外观并降低了FMD病变的严重程度(P <0.05),而且还提供了全面的保护豚鼠。实际上,分别在10和5μg免疫组中分别有六只和六只豚鼠中的两只得到了完全保护。这些结果表明,基于复制酶的DNA疫苗的开发可能提供一种有前途的方法,作为控制口蹄疫的替代疫苗策略。

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