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基于免疫信息学的 2009 年 A (H1N1) 病毒神经氨酸酶的线性 B 细胞表位作图。

Linear B-cell epitope mapping of neuraminidases of the 2009 A H1N1 viruses based on immunoinformatics.

机构信息

Key Laboratory for Emergency Pathogen Detection, Center for Disease Control and Prevention of Guangdong Province, Guangzhou 510300, China.

出版信息

Vaccine. 2011 Feb 1;29(6):1278-82. doi: 10.1016/j.vaccine.2010.11.080. Epub 2010 Dec 8.

Abstract

The 2009 A H1N1 viruses have spread throughout the world, as the viral neuraminidase (NA) is a receptor-destroying enzyme, removing sialic acid from carbohydrate chains attached to NA, and releasing the viruses from infected cells. In this study, the NA genes of Guangdong viruses were sequenced, then their B-cell epitopes were predicted, screened and assessed based on immunoinformatics. The antisera were raised in rabbits against five linear synthetic peptides spanning the NA protein of 2009 A H1N1. Five peptides, LR17, SS12, DP9, DS11 and DI14, respectively, are capable of eliciting neutralizing antibodies against 2009 A H1N1 in the in vitro microneutralization assay. DI14 was identified to be particularly potent in eliciting a neutralizing antibody titer comparable to that obtained with a whole virion-immunized serum. Immunization of rabbit with either five peptides triggered a 2009 A H1N1-specific antibody response as high as that obtained with the whole virion as immunogen. Alignment with databases showed that the amino acid residues of five epitope peptides are highly conserved among the NA sequences of 2009 A H1N1 strains isolated from the world. Altogether, these data indicate that LR17, SS12, DP9, DS11 and DI14 represent a promising candidate for an effective synthetic peptide-based vaccine against 2009 A H1N1 viruses.

摘要

2009 年甲型 H1N1 病毒已在全球范围内传播,因为病毒神经氨酸酶 (NA) 是一种受体破坏酶,可从与 NA 相连的碳水化合物链上去除唾液酸,并将病毒从受感染的细胞中释放出来。在这项研究中,对广东病毒的 NA 基因进行了测序,然后基于免疫信息学预测、筛选和评估了它们的 B 细胞表位。针对跨越 2009 年甲型 H1N1 神经氨酸酶蛋白的五个线性合成肽,用兔抗体制备了抗血清。LR17、SS12、DP9、DS11 和 DI14 五个肽段分别能够在体外微量中和试验中诱导针对 2009 年甲型 H1N1 的中和抗体。DI14 被鉴定为在诱导中和抗体滴度方面特别有效,其滴度可与用整个病毒免疫的血清获得的滴度相媲美。用五个肽段中的任何一个对兔进行免疫,均可触发与用整个病毒作为免疫原获得的一样高的 2009 年甲型 H1N1 特异性抗体反应。与数据库的比对表明,五个表位肽的氨基酸残基在从世界各地分离的 2009 年甲型 H1N1 株的 NA 序列中高度保守。总的来说,这些数据表明 LR17、SS12、DP9、DS11 和 DI14 代表了针对 2009 年甲型 H1N1 病毒的有效合成肽疫苗的有前途的候选物。

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