Aggregation Prone Regions in Antibody Sequences Raised Against Vibrio cholerae: A Bioinformatic Approach

(E-pub Ahead of Print)

Author(s): Zakia Akter, Anamul Haque, Md. Sabir Hossain, Firoz Ahmed, Md Asiful Islam*

Journal Name: Current Bioinformatics

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Abstract:

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

Objectives:In this bioinformatic analysis, we identified the aggregation prone regions (APRs) of different immunogens of antibody sequences (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-TcpA-CT-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 anticholera vaccine.

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

Keywords: Aggregation prone regions, Vibrio cholerae, cholera, antibody sequence, bioinformatics, vaccine

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Article Details

(E-pub Ahead of Print)
DOI: 10.2174/1574893615666200106120504
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