Design of a multi-epitope subunit vaccine for immune-protection against Leishmania parasite

ABSTRACT

Visceral Leishmaniasis (VL) is an insect-borne neglected disease caused by the protozoan parasite Leishmania donovani. In the absence of a commercial vaccine against VL, chemotherapy is currently the only option used for the treatment of VL. Vaccination has been considered as the most effective and powerful tool for complete eradication and control of infectious diseases. In this study, we aimed to design a peptide-based vaccine against L. donovani using immuno-bioinformatic tools. We identified 6 HTL, 18 CTL, and 25 B-cell epitopes from three hypothetical membrane proteins of L. donovani. All these epitopes were used to make a vaccine construct along with linkers. An adjuvant was also added at the N-terminal to enhance its immunogenicity. After that, we checked the quality of this vaccine construct and found that it is nontoxic, nonallergic, and thermally stable. A 3D structure of the vaccine construct was also generated by homology modeling to evaluate its interaction with innate immune receptors (TLR). Molecular docking was performed, which confirmed its binding with a toll-like receptor-2 (TLR-2). The stability of vaccine-TLR-2 complex and underlying interactions were evaluated using molecular dynamic simulation. Lastly, we carried out in silico cloning to check the expression of the final designed vaccine. The designed vaccine construct needs further experimental and clinical investigations to develop it as a safe and effective vaccine against VL infection.

KEYWORDS:

• Hypothetical proteins
• peptide vaccine
• epitopes
• MHC
• visceral leishmaniasis
• molecular dynamics simulation, Immunoinformatics

Acknowledgments

The authors (SY, JP, VKD) are thankful to IIT-BHU for infrastructure. The author (SY) gratefully acknowledges the financial support from SERB for providing an N-PDF fellowship (PDF/2016/003186).

Author contributions

The protocol was designed by S.Y, V.K.D.

The methodology was performed by S.Y., J.P., H.S., K.C.D.

Data analyzed by S. Y. H.S.

The manuscript was written by S.Y., J.P.

The manuscript was refined by S. Y., V.K.D., T.T.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by the Science and Engineering Research Board [PDF/2016/003186].