Development of a tetravalent subunit vaccine against dengue virus through a vaccinomics approach

Front Immunol. 2023 Nov 17:14:1273838. doi: 10.3389/fimmu.2023.1273838. eCollection 2023.

Abstract

Dengue virus infection (DVI) is a mosquito-borne disease that can lead to serious morbidity and mortality. Dengue fever (DF) is a major public health concern that affects approximately 3.9 billion people each year globally. However, there is no vaccine or drug available to deal with DVI. Dengue virus consists of four distinct serotypes (DENV1-4), each raising a different immunological response. In the present study, we designed a tetravalent subunit multi-epitope vaccine, targeting proteins including the structural protein envelope domain III (EDIII), precursor membrane proteins (prM), and a non-structural protein (NS1) from each serotype by employing an immunoinformatic approach. Only conserved sequences obtained through a multiple sequence alignment were used for epitope mapping to ensure efficacy against all serotypes. The epitopes were shortlisted based on an IC50 value <50, antigenicity, allergenicity, and a toxicity analysis. In the final vaccine construct, overall, 11 B-cell epitopes, 10 HTL epitopes, and 10 CTL epitopes from EDIII, prM, and NS1 proteins targeting all serotypes were selected and joined via KK, AAY, and GGGS linkers, respectively. We incorporated a 45-amino-acid-long B-defensins adjuvant in the final vaccine construct for a better immunogenic response. The vaccine construct has an antigenic score of 0.79 via VaxiJen and is non-toxic and non-allergenic. Our refined vaccine structure has a Ramachandran score of 96.4%. The vaccine has shown stable interaction with TLR3, which has been validated by 50 ns of molecular dynamics (MD) simulation. Our findings propose that a designed multi-epitope vaccine has substantial potential to elicit a strong immune response against all dengue serotypes without causing any adverse effects. Furthermore, the proposed vaccine can be experimentally validated as a probable vaccine, suggesting it may serve as an effective preventative measure against dengue virus infection.

Keywords: MD simulation; docking; immunoinformatics; multi-epitope vaccine; proteins; subunit vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dengue Virus*
  • Dengue* / prevention & control
  • Epitopes, B-Lymphocyte
  • Humans
  • Vaccines, Combined
  • Vaccines, Subunit
  • Virus Diseases*

Substances

  • Vaccines, Combined
  • Vaccines, Subunit
  • Epitopes, B-Lymphocyte

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. We would like to acknowledge the Department of Biological Sciences at the National University of Medical Sciences (NUMS), Rawalpindi, Pakistan, for providing us with the facilities and support to publish this article. The authors extend their appreciation to the Higher Education Commission of Pakistan National Research Program for Universities (NRPU; HEC-Ref No: 20-15361/NRPU/R&D/HEC/2021 2021) for funding this study.