Zakia Akter, Anamul Haque, Md. Sabir Hossain, Firoz Ahmed and Md Asiful Islam*
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.
Aggregation prone regions, Vibrio cholerae, cholera, antibody sequence, bioinformatics, vaccine
Department of Biochemistry and Molecular Biology, Gono Bishwabidyalay, Savar, Dhaka 1344, Biomedical Data Science and Informatics Program, School of Computing, Clemson University, Clemson, SC, Department of Biochemistry and Molecular Biology, Jahangirnagar University, Savar, Dhaka 1342, Molecular and Serodiagnostic Laboratory, International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR, B), Dhaka, Department of Haematology, School of Medical Sciences, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan