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Reverse vaccinology-based multi-epitope vaccine design against Indian group A rotavirus targeting VP7, VP4, and VP6
Pooja Rani Kuri1, Pranab Goswami1
1Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Assam, 781039, India.
Insights
A novel multiepitope vaccine targeting rotavirus A (RVA) shows promise for preventing infantile gastroenteritis. Computational analysis suggests this vaccine can elicit both humoral and cell-mediated immunity, offering a potential solution to current vaccine limitations.
Area of Science:
- Virology
- Immunology
- Vaccine Development
Background:
- Rotavirus A (RVA) causes severe gastroenteritis in children globally, especially in low-income countries.
- Current vaccines have limited efficacy and potential side effects like intussusception due to RVA's genetic diversity.
- The prevalent Indian RVA strain is G1P[8].
Purpose of the Study:
- To design and computationally evaluate a novel multiepitope vaccine against the prevalent Indian RVA strain.
- To identify conserved RVA epitopes for vaccine development.
- To assess the vaccine's potential immunogenicity and safety through in silico methods.
Main Methods:
- Phylogenetic analysis of Indian RVA molecular data.
- Identification and selection of conserved VP7, VP4, and VP6 capsid protein epitopes based on antigenicity, non-allergenicity, non-toxicity, and stability.
- In silico vaccine design, including epitope linkage, adjuvant incorporation, docking, normal mode analysis, and immune simulation.
Main Results:
- G1P[8] identified as the predominant RVA strain in India.
- Twenty stable, non-allergenic, and non-toxic epitopes were selected.
- The in silico designed vaccine demonstrated structural stability and favorable interactions with host immune receptors (integrins and TLRs).
- Immune simulations predicted the vaccine's ability to induce both humoral and cell-mediated immune responses.
Conclusions:
- The designed RVA multiepitope vaccine is a promising immunogen with potential efficacy against rotavirus infection.
- Computational findings support further development of this vaccine candidate.
- This approach may overcome limitations of existing RVA vaccines.
Abstract:
Rotavirus, a primary contributor to severe cases of infantile gastroenteritis on a global scale, results in significant morbidity and mortality in the under-five population, particularly in middle to low-income countries, including India. WHO-approved live-attenuated vaccines are linked to a heightened susceptibility to intussusception and exhibit low efficacy, primarily attributed to the high genetic diversity of rotavirus, varying over time and across different geographic regions. Herein, molecular data on Indian rotavirus A (RVA) has been reviewed through phylogenetic analysis, revealing G1P[8] to be the prevalent strain of RVA in India. The conserved capsid protein sequences of VP7, VP4 and VP6 were used to examine helper T lymphocyte, cytotoxic T lymphocyte and linear B-cell epitopes. Twenty epitopes were identified after evaluation of factors such as antigenicity, non-allergenicity, non-toxicity, and stability. These epitopes were then interconnected using suitable linkers and an N-terminal beta defensin adjuvant. The in silico designed vaccine exhibited structural stability and interactions with integrins (αvβ3 and αIIbβ3) and toll-like receptors (TLR2 and TLR4) indicated by docking and normal mode analyses. The immune simulation profile of the designed RVA multiepitope vaccine exhibited its potential to trigger humoral as well as cell-mediated immunity, indicating that it is a promising immunogen. These computational findings indicate potential efficacy of the designed vaccine against rotavirus infection.
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