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Aggregation Prone Regions in Antibody Sequences Raised Against Vibrio cholerae: A Bioinformatic Approach
Current Bioinformatics ( IF 4 ) Pub Date : 2020-10-31 , DOI: 10.2174/1574893615666200106120504
Zakia Akter 1 , Anamul Haque 2 , Md. Sabir Hossain 3 , Firoz Ahmed 4 , Md Asiful Islam 5
Affiliation  

Background: Cholera, a diarrheal illness, causes millions of deaths worldwide due to large outbreaks. The monoclonal antibody used as therapeutic purposes of cholera is prone to be unstable due to various factors including self-aggregation.

Objectives: In this bioinformatic analysis, we identified the aggregation prone regions (APRs) of antibody sequences of different immunogens (i.e., CTB, ZnM-CTB, ZnP-CTB, TcpA-CT-CTB, ZnM-TcpA-CT-CTB, ZnP-TcpA-CT-CTB, ZnM-TcpA, ZnP-TcpA, TcpA-CT-TcpA, ZnM-TcpACT- TcpA, ZnP-TcpA-CT-TcpA, Ogawa, Inaba and ZnM-Inaba) raised against Vibrio cholerae.

Methods: To determine APRs in antibody sequences that were generated after immunizing Vibrio cholerae immunogens on Mus musculus, a total of 94 sequences were downloaded as FASTA format from a protein database and the algorithms such as Tango, Waltz, PASTA 2.0, and AGGRESCAN were followed to analyze probable APRs in all of the sequences.

Results: A remarkably high number of regions in the monoclonal antibodies were identified to be APRs which could explain a cause of instability/short term protection of the anticholera vaccine.

Conclusion: To increase the stability, it would be interesting to eliminate the APR residues from the therapeutic antibodies in such a way that the antigen-binding sites or the complementarity determining region loops involved in antigen recognition are not disrupted.



中文翻译:

霍乱弧菌抗体序列中的聚集倾向区域:一种生物信息学方法。

背景:霍乱是一种腹泻性疾病,由于大规模爆发而在全球范围内造成数百万人死亡。由于包括自聚集在内的各种因素,用作霍乱治疗目的的单克隆抗体易于不稳定。

目的:在这项生物信息学分析中,我们确定了不同免疫原(即CTB,ZnM-CTB,ZnP-CTB,TcpA-CT-CTB,ZnM-TcpA-CT-CTB,ZnP)的抗体序列的聚集倾向区域(APR) -TcpA-CT-CTB,ZnM-TcpA,ZnP-TcpA,TcpA-CT-TcpA,ZnM-TcpACT-TcpA,ZnP-TcpA-CT-TcpA,Ogawa,Inaba和ZnM-Inaba)针对霍乱弧菌提出。

方法:为了确定小家鼠霍乱弧菌免疫原免疫后产生的抗体序列中的APR,从蛋白质数据库中以FASTA格式下载了94个序列,并遵循了Tango,Waltz,PASTA 2.0和AGGRESCAN等算法分析所有序列中可能的APR。

结果:单克隆抗体中大量的区域被确定为APR,这可能解释了抗霍乱疫苗不稳定/短期保护的原因。

结论:为了提高稳定性,从治疗性抗体中消除APR残基的方式应引起人们的注意,即不破坏涉及抗原识别的抗原结合位点或互补决定区环。

更新日期:2020-10-31
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