Gauche+ side-chain orientation as a key factor in the search for an immunogenic peptide mixture leading to a complete fully protective vaccine
Patarroyo, Manuel A.
Patarroyo, Manuel E.
"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."
immunologic ; falciparum ; Malaria vaccine ; protozoan ; 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 ; Adjuvants ; Amino acid sequence ; Animals ; Antibodies ; Antibody formation ; Aotus trivirgatus ; Binding sites ; Hla-dr beta-chains ; Malaria vaccines ; Malaria ; Molecular sequence data ; Oligopeptides ; Protein conformation ; Antimalarial vaccine ; Peptide mixtures ; Protective immunity ;
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