Vaccinomics Approach for Multi-Epitope Vaccine Design against Group A Rotavirus Using VP4 and VP7 Proteins
Muhammad Usman,
Aaima Ayub,
Sabahat Habib,
Muhammad Suleman Rana,
Zaira Rehman,
Ali Zohaib,
Syed Babar Jamal,
Arun Kumar Jaiswal,
Bruno Silva Andrade,
Vasco de Carvalho Azevedo,
Muhammad Faheem,
Aneela Javed
Affiliations
Muhammad Usman
Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad 44000, Pakistan
Aaima Ayub
Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad 44000, Pakistan
Sabahat Habib
Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad 44000, Pakistan
Muhammad Suleman Rana
Department of Virology, National Institute of Health, Islamabad 45500, Pakistan
Zaira Rehman
Department of Virology, National Institute of Health, Islamabad 45500, Pakistan
Ali Zohaib
Department of Microbiology, The Islamia University of Bahawalpur, Baghdad-ul-Jadeed Campus, Bahawalpur 63100, Pakistan
Syed Babar Jamal
Department of Biological Sciences, National University of Medical Sciences, Rawalpindi 46000, Pakistan
Arun Kumar Jaiswal
Laboratory of Cellular and Molecular Genetics (LGCM), PG Program in Bioinformatics, Department of Genetics, Ecology, and Evolution, Institute of Biological Sciences, Federal University of Minas Gerais (UFMG), Belo Horizonte 31270-901, Brazil
Bruno Silva Andrade
Laboratory of Bioinformatics and Computational Chemistry, State University of Southwest of Bahia, Bahia 45083-900, Brazil
Vasco de Carvalho Azevedo
Laboratory of Cellular and Molecular Genetics (LGCM), PG Program in Bioinformatics, Department of Genetics, Ecology, and Evolution, Institute of Biological Sciences, Federal University of Minas Gerais (UFMG), Belo Horizonte 31270-901, Brazil
Muhammad Faheem
Department of Biological Sciences, National University of Medical Sciences, Rawalpindi 46000, Pakistan
Aneela Javed
Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad 44000, Pakistan
Rotavirus A is the most common cause of Acute Gastroenteritis globally among children <5 years of age. Due to a segmented genome, there is a high frequency of genetic reassortment and interspecies transmission which has resulted in the emergence of novel genotypes. There are concerns that monovalent (Rotarix: GlaxoSmithKline Biologicals, Rixensart, Belgium) and pentavalent (RotaTeq: MERCK & Co., Inc., Kenilworth, NJ, USA) vaccines may be less effective against non-vaccine strains, which clearly shows the demand for the design of a vaccine that is equally effective against all circulating genotypes. In the present study, a multivalent vaccine was designed from VP4 and VP7 proteins of RVA. Epitopes were screened for antigenicity, allergenicity, homology with humans and anti-inflammatory properties. The vaccine contains four B-cell, three CTL and three HTL epitopes joined via linkers and an N-terminal RGD motif adjuvant. The 3D structure was predicted and refined preceding its docking with integrin. Immune simulation displayed promising results both in Asia and worldwide. In the MD simulation, the RMSD value varied from 0.2 to 1.6 nm while the minimum integrin amino acid fluctuation (0.05–0.1 nm) was observed with its respective ligand. Codon optimization was performed with an adenovirus vector in a mammalian expression system. The population coverage analysis showed 99.0% and 98.47% in South Asia and worldwide, respectively. These computational findings show potential against all RVA genotypes; however, in-vitro/in-vivo screening is essential to devise a meticulous conclusion.
