Reconnoitering Mycobacterium tuberculosis lipoproteins to design subunit vaccine by immunoinformatics approach

Muhammad Ahsan Naeem, Muhammad Muzammal Adeel, Ayesha Kanwal, Sajjad Ahmad, Waqas Ahmad, Qaiser Akram, Asif Saleh, Waqas Ahmed

Abstract


Background: Tuberculosis is an aerosol transmitted disease of human beings caused by Mycobacterium tuberculosis (Mtb). The only available vaccine for Mtb is Bacillus Calmette-Guérin (BCG). Currently no alternative or booster is available for BCG. The objective of this predictive approach was based on binding of MHC-I and MHC-II and B cell epitopes of Mtb for mouse host.

Methods: Immunoinformatics approach was used to design subunit vaccine (SV) by joining 8 MHC-I bindings, 6 MHC-II bindings, and 8 B-Cell epitopes with AAV, GPGPG, and KK amino acid linkers, respectively. The efficacy of the SV was enhanced through Mtb protein Rv3763 (LpqH, PDB ID= 4ZJM) as an adjuvant at the N-terminal of SV. The in silico analyses evaluated the SV to predict allergenicity, antigenicity, and physico-chemical properties.

Results: Predictions revealed that SV is non-allergic and highly antigenic. The physico-chemical analysis showed that the SV was stable and basic in nature. The three-dimensional structure of SV was stable with a high binding affinity against the mouse TLR2 receptor. In silico cloning suggested the effective transformation of SV into the eukaryotic expression vector.

Conclusion: This study permits preclinical validation of the designed SV in mouse host to confirm its immunogenic potential and efficacy, which will help in controlling tuberculosis.

Keywords: Immunoinformatics; Docking; Subunit vaccine; Lipoprotein; Tuberculosis 


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References


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