Comprehensive immunoinformatics analysis and chimeric multi-epitope vaccine design targeting VP1 capsid protein of poliovirus type 3

Poliomyelitis is caused by poliovirus, a member of the genus Enterovirus in the family Picornaviridae. Oral and inactivated poliovirus vaccines have substantially reduced disease worldwide; however, limitations include incomplete intestinal immunity after inactivated vaccine and the rare emergence of vaccine-derived strains after oral vaccine, supporting investigation of non-replicating vaccine platforms. Poliomyelitis is classified into three distinct forms: mild disease (abortive poliomyelitis), paralytic poliomyelitis, and aseptic meningitis (nonparalytic poliomyelitis). Severe neurological complications, including irreversible paralysis, have affected thousands of individuals worldwide. Polio is prevented via vaccination, namely with the inactivated and attenuated oral polio vaccine. Although existing vaccines have driven global eradication, IPV provides limited intestinal mucosal immunity, and OPV can rarely be associated with vaccine-derived poliovirus, motivating evaluation of a non-replicating vaccine platform.Abstruct. This study used immunoinformatics to design and preliminarily evaluate a chimeric multi-epitope vaccine candidate targeting the VPI capsid protein of poliovirus type 3. The VPI sequence (NCB accession number ABG78772.1) was used for linear B-cell, MHC-class I, and MHC-class II epitope prediction and safty filtering. Selected epitopes were joined with defined linkers and an N-terminal human beta-defensin adjuvant. The resulting construct was evaluated for physicochemical properties, structural quality, predicted HLA population coverage, rigid-body docking with TLR3, normal-mode behaviour, and simulated immune responses. Codon adaptation and in silico cloning were also performed to evaluate the potential expression feasibility of the vaccine construct. This study used immunoinformatics to design and preliminarily evaluate a chimeric multi-epitope vaccine candidate targeting the VPI capsid protein of poliovirus type 3. Four B-cell epitopes, twenty-six cytotoxic T-lymphocyte epitopes, twenty helper T-lymphocyte epitopes, including EAAAK, GPGPG, and AAY linkers and β-defensin, were assembled into a 569-amino-acid construct. The construct was predicted to be antigenic, non-allergenic, non-toxic, and to show favourable physicochemical properties, including hydrophilic characteristics. Combined MCH-I and MCH-II epitopes predicted global HLA population coverage of 98.52%. CLustPro identified a top-ranked docked cluster with a weighted score of -1134; this score ranks models within the docking run and is not a binding free energy or dissociation constant. C-ImmSim predicted secondary humoral and cellular responses after booster doses, while codon analysis suggested compatibility with expression in Escherichia coli. Conclusion: The computational findings support the construct as a preliminary candidate for further study. They do not establish immunogenicity, safety, protective efficacy, receptor activation, or expression, all of which require experimental validation and in vitro and in vivo testing before biological conclusions can be drawn.