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感染和无细胞疫苗接种后针对百日咳毒素的表位特异性抗体的差异。

Differences in epitope-specific antibodies to pertussis toxin after infection and acellular vaccinations.

作者信息

Knuutila Aapo, Dalby Tine, Barkoff Alex-Mikael, Jørgensen Charlotte Sværke, Fuursted Kurt, Mertsola Jussi, Markey Kevin, He Qiushui

机构信息

Institute of Biomedicine University of Turku Turku Finland.

Statens Serum Institut Copenhagen Denmark.

出版信息

Clin Transl Immunology. 2020 Aug 2;9(8):e1161. doi: 10.1002/cti2.1161. eCollection 2020.

DOI:10.1002/cti2.1161
PMID:32765879
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7396262/
Abstract

OBJECTIVES

Pertussis toxin (PT) is a component of all acellular pertussis vaccines. PT must be detoxified to be included in acellular vaccines, which results in conformational changes in the functional epitopes of PTs. Therefore, induced epitope-specific antibodies to PT may vary after vaccinations or natural infections, and this information could reveal biomarkers implicated for protection and successful immunisation.

METHODS

Pertussis toxin epitope-specific antibodies in sera from 152 vaccinated children and 72 serologically confirmed patients were tested with a blocking ELISA, based on monoclonal antibodies that target protective PT epitopes.

RESULTS

All study groups induced considerable antibody titres to subunit 1 (S1). Of interest, S3 7E10-specific antibodies were present in patients, but not after vaccinations ( < 0.001). The impact of glutaraldehyde treatment of PT was visible on epitope 1D7 (S1), whereas epitopes 1B7 (S1) and 10D (S1) were more preserved. Antibodies to these epitopes were higher after three primary vaccine doses than after a single booster dose.

CONCLUSION

The high amount of 7E10-specific antibodies in patients suggests this epitope might be functionally relevant in protection. The overall characteristics of epitope-specific antibodies are influenced by infection or vaccination background, by the used detoxification method of PT and by the amount of the toxin used in immunisation.

摘要

目的

百日咳毒素（PT）是所有无细胞百日咳疫苗的成分之一。PT必须经过解毒才能用于无细胞疫苗，这会导致PT功能表位的构象发生变化。因此，接种疫苗或自然感染后，诱导产生的针对PT的表位特异性抗体可能会有所不同，而这些信息可能揭示与保护和成功免疫相关的生物标志物。

方法

采用基于靶向保护性PT表位的单克隆抗体的阻断ELISA法，检测了152名接种疫苗儿童和72名血清学确诊患者血清中百日咳毒素表位特异性抗体。

结果

所有研究组均诱导产生了针对亚基1（S1）的较高抗体滴度。有趣的是，患者体内存在S3 7E10特异性抗体，但接种疫苗后则不存在（P<0.001）。戊二醛处理PT对表位1D7（S1）有明显影响，而表位1B7（S1）和10D（S1）则保存得较好。三次初级疫苗接种后针对这些表位的抗体水平高于单次加强剂量接种后。

结论

患者体内大量的7E10特异性抗体表明该表位可能在保护中具有功能相关性。表位特异性抗体的总体特征受感染或疫苗接种背景、PT所用解毒方法以及免疫所用毒素量的影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5bc/7396262/b6cef1adcf6a/CTI2-9-e1161-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5bc/7396262/b2d9921ade12/CTI2-9-e1161-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5bc/7396262/143724e11724/CTI2-9-e1161-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5bc/7396262/8904d8dfe690/CTI2-9-e1161-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5bc/7396262/21859ba01f21/CTI2-9-e1161-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5bc/7396262/b6cef1adcf6a/CTI2-9-e1161-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5bc/7396262/b2d9921ade12/CTI2-9-e1161-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5bc/7396262/143724e11724/CTI2-9-e1161-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5bc/7396262/8904d8dfe690/CTI2-9-e1161-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5bc/7396262/21859ba01f21/CTI2-9-e1161-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5bc/7396262/b6cef1adcf6a/CTI2-9-e1161-g005.jpg

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