Harnessing Immunoinformatic for HIV-2: Multi-Epitope Vaccine Design Targeting the env Protein (CAA28914.1)

Abstract

A[Formula][s][t]rac[t]O_ST_ABSBackgroundC_ST_ABSHIV-2 is a major threat to human health because of its rising global incidence. As a result, the development of effective immunostimulatory molecules for vaccine design against HIV-2 has garnered increasing interest. ObjectiveThe main objective was to make a multi Targeting epitoptpic vaccine for HIV-2 envelope protein using immunoinformatic approaches. MethodsSequence were retrieved from NCBI. B & T-cell epitopes were predicted with assessments of antigenicity, allergenicity, and cytokine-inducing potential. Physicochemical properties, docking studies, and codon optimization for expression was also performed using different software tools. FindingsThe designed vaccine construct (477 amino acids, molecular weight of 54 kDa) showed a strong antigenicity with VaxiJen score of 0.7146 which was non-allergenic and non-toxic with favorable physicochemical parameters (Mw: [~]53 kDa; pI: 9.89; stable and soluble). The construct demonstrated broad population coverage for MHC-I (West Africa: 69.51%, Pakistan: 78%, Global: 82%) and MHC-II (Global: 99%). Out of 16 peptides analyzed, 7 were predicted as IL-10 inducers 2 as a strong IL-4 inducer, and 2 were IFN-{gamma} inducing epitopes. Structural validation confirmed high-quality folding (96% residues in favored regions; ERRAT score: 84.35). Docking results revealed a strong binding affinity to TLR2 (PDB ID: 2AOZ; energy: -1481.1 kcal/mol). MD simulation confirmed structural stability (RMSD [~]1.37 nm; Rg [~]3.65 nm). Immune simulation predicted robust humoral and cellular responses with sustained antibody production and cytokine activation. Codon optimization is given to a Codon Adaptation Index (CAI) of 0.628 with a guanine (G) and cytosine (C) nucleotides content of 65.48%, suitable for E. coli expression. ConclusionThis vaccine construct is immunogenic, stable, and able to elicit both antibody-mediated immunity and cell-mediated immunity responses. Furthermore, In-vitro or In-Vivo Validations are recommended to verify its effectiveness O_FIG O_LINKSMALLFIG WIDTH=178 HEIGHT=200 SRC="FIGDIR/small/658249v1_ufig1.gif" ALT="Figure 1"> View larger version (64K): org.highwire.dtl.DTLVardef@c3660corg.highwire.dtl.DTLVardef@60cc61org.highwire.dtl.DTLVardef@10a1e87org.highwire.dtl.DTLVardef@15a5aa1_HPS_FORMAT_FIGEXP M_FIG C_FIG