Research Article

Targeting ‘immunogenic hotspots’ in Dengue and Zika virus: an in silico approach to a common vaccine candidate

https://orcid.org/0000-0001-6140-2394

School of Medical Science & Technology, Indian Institute of Technology Kharagpur, Kharagpur, 721302, India

School of Bioscience, Indian Institute of Technology Kharagpur, Kharagpur, 721302, India

‡Authors contributed equally to the paper and share first authorship.

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Debangshu Mukherjee‡

https://orcid.org/0000-0002-3586-1877

School of Medical Science & Technology, Indian Institute of Technology Kharagpur, Kharagpur, 721302, India

‡Authors contributed equally to the paper and share first authorship.

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Kheerthana Duraivelan

https://orcid.org/0000-0001-5496-1884

School of Bioscience, Indian Institute of Technology Kharagpur, Kharagpur, 721302, India

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Vanshika Malviya

https://orcid.org/0000-0002-7669-6142

Department of Biotechnology, Indian Institute of Technology Kharagpur, Kharagpur, 721302, India

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Pratap Parida

https://orcid.org/0000-0002-8193-335X

School of Medical Science & Technology, Indian Institute of Technology Kharagpur, Kharagpur, 721302, India

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Gayatri Mukherjee

*Author for correspondence:

E-mail Address: gayatri.mukherjee@smst.iitkgp.ac.in

https://orcid.org/0000-0003-3199-7213

School of Medical Science & Technology, Indian Institute of Technology Kharagpur, Kharagpur, 721302, India

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Published Online:24 Feb 2023https://doi.org/10.2217/fvl-2022-0104

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Abstract

Aim: Dengue and Zika viruses cause significant mortality globally. Considering high sequence similarity between the viral proteins, we designed common multi-epitope vaccine candidates against these pathogens. Methods: We identified multiple T and B cell epitope-rich conserved ‘immunogenic hotspots’ from highly antigenic and phylogenetically related viral proteins and used these to design the multi-epitope vaccine (MEV) candidates, ensuring high global population coverage. Results: Four MEV candidates containing conserved immunogenic hotspots from E and NS5 proteins with the highest structural integrity could favorably interact with TLR4-MD2 complex in molecular docking studies, indicating activation of TLR-mediated immune responses. MEVs also induced memory responses in silico, hallmarks of a good vaccine candidate. Conclusion: Conserved immunogenic hotspots can be utilized to design cross-protective MEV candidates.

Plain language summary

Dengue and Zika viruses cause significant illness globally. Interestingly, they belong to the same family of viruses and therefore are closely related to each other. The immune response developed against one can often protect against the other or in some cases exacerbate the infection. Considering these characteristics of these viruses, we have designed a common vaccine candidate using bioinformatics-based tools, taking care to exclude the infection enhancing factors.

Tweetable abstract

Common multi-epitope vaccine candidates against Dengue viral strains and Zika virus have been designed in silico by utilizing multiple T and B-cell epitope-rich ‘immunogenic hotspots’, derived from the most antigenic and phylogenetically-related conserved proteins.

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Papers of special note have been highlighted as: •• of considerable interest

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Vol. 18, No. 2

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Received 20 May 2022

Accepted 11 January 2023

Published online 24 February 2023

Published in print February 2023

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Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.futuremedicine.com/doi/suppl/10.2217/fvl-2022-0104

Author contributions

DJ Mahata, D Mukherjee and K Duraivelan conducted experiments, performed data analysis and co-authored the paper. V Malviya and P Parida conducted experiments. G Mukherjee conceptualized the idea of the paper, performed data analysis, received the funding, co-authored the paper. DJ Mahata and D Mukherjee contributed equally to the paper.

Acknowledgments

The authors acknowledge National Supercomputing Mission (NSM) for providing computing resources of “PARAM Shakti” at IIT Kharagpur, which is implemented by C-DAC and supported by the Ministry of Electronics and Information Technology (MeitY) and Department of Science and Technology (DST), Government of India. The authors also thank D Samanta for his critical inputs, which improved the work significantly.

Financial & competing interests disclosure

This work was funded by SERB, Govt of India (ECR/2017/002073). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

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