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


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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