title: IMPIPS: the immune protection-inducing protein structure concept in the search for steric-electron and topochemical principles for complete fully-protective chemically synthesised vaccine development.
abstract: Determining immune protection-inducing protein structures (IMPIPS) involves defining the stereo-electron and topochemical characteristics which are essential in MHC-p-TCR complex formation. Modified high activity binding peptides (mHABP) were thus synthesised to produce a large panel of IMPIPS measuring 26.5 ±3.5Å between the farthest atoms fitting into Pockets 1 to 9 of HLA-DRβ1* structures. They displayed a polyproline II-like (PPIIL) structure with their backbone O and N atoms orientated to establish H-bonds with specific residues from HLA-DRβ1*-peptide binding regions (PBR). Residues having specific charge and gauche+ orientation regarding p3χ1, p5χ2, and p7χ1 angles determined appropriate rotamer orientation for perfectly fitting into the TCR to induce an appropriate immune response. Immunological assays in Aotus monkeys involving IMPIPS mixtures led to promising results; taken together with the aforementioned physicochemical principles, non-interfering, long-lasting, protection-inducing, multi-epitope, multistage, minimal subunit-based chemically-synthesised peptides can be designed against diseases scourging humankind.
authors: Fundación Instituto de Inmunología de Colombia (FIDIC), Bogotá, Colombia; Universidad Nacional de Colombia, Bogotá, Colombia.
authors: Manuel Elkin
authors: ME
authors: Patarroyo
authors: Fundación Instituto de Inmunología de Colombia (FIDIC), Bogotá, Colombia; Universidad del Rosario, Bogotá, Colombia.
authors: Adriana
authors: A
authors: Bermúdez
authors: Fundación Instituto de Inmunología de Colombia (FIDIC), Bogotá, Colombia; Universidad del Rosario, Bogotá, Colombia.
authors: Martha Patricia
authors: MP
authors: Alba
authors: Fundación Instituto de Inmunología de Colombia (FIDIC), Bogotá, Colombia; Universidad del Rosario, Bogotá, Colombia.
authors: Magnolia
authors: M
authors: Vanegas
authors: Fundación Instituto de Inmunología de Colombia (FIDIC), Bogotá, Colombia.
authors: Armando
authors: A
authors: Moreno-Vranich
authors: Fundación Instituto de Inmunología de Colombia (FIDIC), Bogotá, Colombia.
authors: Luis Antonio
authors: LA
authors: Poloche
authors: Fundación Instituto de Inmunología de Colombia (FIDIC), Bogotá, Colombia; Universidad del Rosario, Bogotá, Colombia.
authors: Manuel Alfonso
authors: MA
authors: Patarroyo
mesh_terms: D000818:Animals; D004583:Electrons; D000882:Haplorhini; D017780:Malaria Vaccines / Q000737:chemistry; D011487:Protein Conformation; D014614:Vaccines, Synthetic / Q000737:chemistry*
chemical_list: D017780:Malaria Vaccines; D014614:Vaccines, Synthetic