Gauche+ side-chain orientation as a key factor in the search for an immunogenic peptide mixture leading to a complete fully protective vaccine

Topological and stereo-electron characteristics are essential in major histocompability class II-peptide-T-cell receptor (MHC-p-TCR) complex formation for inducing an appropriate immune response. Modified high activity binding peptides (mHABPs) were synthesised for complete full protection antimalarial vaccine development producing a large panel of individually fully protection-inducing protein structures (FPIPS) and very high long-lasting antibody-inducing (VHLLAI) mHABPs. Most of those which did not interfere, compete, inhibit or suppress their individual VHLLAI or FPIPS activity contained or displayed a polyproline II-like (PPIIL) structure when mixed. Here we show that amino acid side-chains located in peptide binding region (PBR) positions p3 and p7 displayed specific electron charges and side-chain gauche+ orientation for interacting with the TCR. Based on the above, and previously described physicochemical principles, non-interfering, long-lasting, full protection-inducing, multi-epitope, multistage, minimal subunit-based chemically synthesised mHABP mixtures can be designed for developing vaccines against diseases scourging humankind, malaria being one of them. © 2014 Elsevier Ltd.

• Fecha de publicación: 2014
• Institución: Universidad del Rosario
• Repositorio: Repositorio EdocUR - U. Rosario
• Idioma: eng
• OAI Identifier: oai:repository.urosario.edu.co:10336/23461
• Acceso en línea: https://doi.org/10.1016/j.vaccine.2014.02.003; https://repository.urosario.edu.co/handle/10336/23461
• Palabra clave: protozoan; immunologic; falciparum; Adjuvants; Antibodies; Malaria; Malaria vaccine; Peptide vaccine; Unclassified drug; Very high long lasting antibody inducing modified high activity binding peptide; Animal experiment; Antibody production; Antibody titer; Aotus; Article; Controlled study; Drug mixture; Enzyme linked immunosorbent assay; Gauche side chain orientation; Genotype; Immune response; Immunofluorescence; Immunogenicity; Nonhuman; Priority journal; Protection; Protein structure; Proton nuclear magnetic resonance; Sporozoite; Vaccination; Western blotting; Antimalarial vaccine; Gauche(+); Peptide mixtures; Protective immunity; ?(1) angle; Amino acid sequence; Animals; Antibody formation; Aotus trivirgatus; Binding sites; Hla-dr beta-chains; Malaria vaccines; Molecular sequence data; Oligopeptides; Protein conformation; Antimalarial vaccine; Peptide mixtures; Protective immunity
• License: Abierto (Texto Completo)