206
Views
1
CrossRef citations to date
0
Altmetric
Research Article

Elucidation of conserved multi-epitope vaccine against Leishmania donovani using reverse vaccinology

& ORCID Icon
Pages 1293-1306 | Received 02 Nov 2022, Accepted 29 Mar 2023, Published online: 13 Apr 2023
 

Abstract

Visceral leishmaniasis (VL) is a tropical disease that causes severe public health problems in humans when untreated. As no licensed vaccine exists against VL, we aimed to formulate a potential MHC-restricted chimeric vaccine construct against this dreadful parasitic disease. Amastin-like protein derived from L. donovani is considered to be stable, immunogenic and non-allergic. A comprehensive established framework was used to explore the set of immunogenic epitopes with estimated population coverage of 96.08% worldwide. The rigorous assessment revealed 6 promiscuous T-epitopes which can plausibly be presented by more than 66 diverse HLA alleles. Further docking and simulation study of peptide receptor complexes identified a strong and stable binding interaction with better structural compactness. The predicted epitopes were combined with appropriate linkers and adjuvant molecules and their translation efficiency was evaluated in pET28+(a), an bacterial expression vector using in-silico cloning. Molecular docking followed by MD simulation study revealed a stable interaction between chimeric vaccine construct with TLRs. Immune simulation of the chimeric vaccine constructs showed an elevated Th1 immune response against both B and T epitopes. With this, the detailed computational analysis suggested that the chimeric vaccine construct can evoke a robust immune response against Leishmania donovani infection. Future studies are required to validate the role of amastin as a promising vaccine target.

Communicated by Ramaswamy H. Sarma

Acknowledgements

We would like to thank Indian Council of Medical research for supporting the project through intramural funding. The authors would like to express their gratitude to IBDC, RCB- Faridabad, India for providing space and runtime environment in HP cluster for MD Simulation study. The authors would also like to express their gratitude to centenary Postdoctoral Fellowship programme of ICMR for supporting Dr. Manas Ranjan Dikhit (3/1/3/PDF/19/2019/HRD).

Authors contribution

Manas Ranjan Dikhit and Abhik Sen designed the research work, performed the experiments. Bioinformatic analysis was completed by Manas Ranjan Dikhit. The first version of the manuscript was written by Manas Ranjan Dikhit and the final version corrected by Abhik Sen. All the authors contributed to the article and approved the manuscript.

Data availability statement

The raw data supporting the conclusion of this article will be made available by the authors, without undue reservation.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.