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全细胞和无细胞百日咳疫苗诱导对博德特氏菌丝状血凝素的有限抗体反应。

Restricted antibody response to Bordetella pertussis filamentous hemagglutinin induced by whole-cell and acellular pertussis vaccines.

机构信息

a Department of Immunology , School of Public Health, Tehran University of Medical Sciences , Tehran , Iran .

b Department of Immunology, School of Medicine , Mazandaran University of Medical Sciences , Sari , Iran .

出版信息

Infect Dis (Lond). 2016 Feb;48(2):127-32. doi: 10.3109/23744235.2015.1093655. Epub 2015 Oct 6.

Abstract

BACKGROUND

Filamentous hemagglutinin (FHA) is a principal virulence factor, an important immunogenic antigen of Bordetella pertussis, and a major component of many acellular pertussis vaccines. In the present study, the human antibody response to different regions of FHA was determined in healthy children and adults vaccinated with either whole-cell or acellular pertussis vaccines.

METHODS

To define the immunodominant regions of FHA, four overlapping recombinant fragments were expressed and produced in Escherichia coli and then purified by His-tagged based affinity chromatography. Two groups comprising healthy preschool children (n = 50) and adults (n = 26) were vaccinated with a single dose of commercial whole-cell and acellular DTaP vaccines, respectively. An antigen-based ELISA was applied to measure serum levels of anti-FHA antibody to both native and recombinant proteins in vaccinated volunteers.

RESULTS

In both groups of vaccinated individuals, the anti-FHA antibody response was mainly directed against epitopes located within a fragment of FHA spanning amino acid residues 1877-2250 of the mature FHA molecule (p < 0.001). No or little antibody was detected against the other recombinant segments of FHA.

CONCLUSION

Our results suggest that the human antibody response to FHA is directed to an immunodominant region located within residues 1877-2250 of the FHA molecule. Characterization and epitope mapping of the major components of acellular pertussis vaccine and future modifications in vaccine formulation may improve its efficacy and protectivity.

摘要

背景

丝状血凝素(FHA)是百日咳博德特氏菌的主要毒力因子、重要免疫原性抗原,也是许多无细胞百日咳疫苗的主要成分。本研究在健康儿童和成人中,用全细胞或无细胞百日咳疫苗接种后,测定了针对 FHA 不同区域的人抗体反应。

方法

为了确定 FHA 的免疫优势区,表达并在大肠杆菌中产生了四个重叠的重组片段,然后通过 His 标记的亲和层析进行纯化。两组健康学龄前儿童(n=50)和成人(n=26)分别用一剂商业全细胞和无细胞 DTaP 疫苗接种。应用抗原 ELISA 法检测接种志愿者血清中针对天然和重组蛋白的抗 FHA 抗体水平。

结果

在两组接种个体中,抗 FHA 抗体反应主要针对位于 FHA 成熟分子 1877-2250 位氨基酸残基的一个片段内的表位(p<0.001)。针对 FHA 的其他重组片段未检测到或很少检测到抗体。

结论

我们的结果表明,人类对 FHA 的抗体反应针对 FHA 分子 1877-2250 位氨基酸残基内的免疫优势区。无细胞百日咳疫苗主要成分的特征和表位作图以及未来疫苗配方的改进可能会提高其疗效和保护力。

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