SM-COLSARSPROT: Highly Immunogenic Supramutational Synthetic Peptides Covering the World’s Population

Fifty ~20–amino acid (aa)–long peptides were selected from functionally relevant SARS-CoV-2 S, M, and E proteins for trial B-21 and another 53 common ones, plus some new ones derived from the virus’ main genetic variants for complementary trial C-21. Peptide selection was based on tremendous SARS-CoV-2 genetic variability for analysing them concerning vast human immunogenetic polymorphism for developing the first supramutational, Colombian SARS-protection (SM-COLSARSPROT), peptide mixture. Specific physicochemical rules were followed, i.e., aa predilection for polyproline type II left-handed (PPIIL) formation, replacing β-branched, aromatic aa, short-chain backbone H-bond-forming residues, π-π interactions (n→π* and π-CH), aa interaction with π systems, and molecular fragments able to interact with them, disrupting PPIIL propensity formation. All these modified structures had PPIIL formation propensity to enable target peptide interaction with human leukocyte antigen-DRβ1* (HLA-DRβ1*) molecules to mediate antigen presentation and induce an appropriate immune response. Such modified peptides were designed for human use; however, they induced high antibody titres against S, M, and E parental mutant peptides and neutralising antibodies when suitably modified and chemically synthesised for immunising 61 major histocompatibility complex class II (MHCII) DNA genotyped Aotus monkeys (matched with their corresponding HLA-DRβ1* molecules), predicted to cover 77.5% to 83.1% of the world’s population. Such chemically synthesised peptide mixture represents an extremely pure, stable, reliable, and cheap vaccine for COVID-19 pandemic control, providing a new approach for a logical, rational, and soundly established methodology for other vaccine development.

• Autores: Patarroyo, Manuel-Alfonso; Patarroyo, Manuel-Elkin; Pabón, Laura; Alba, Martha patricia; Bermúdez, Adriana; Rugeles, María Teresa; Díaz-Arevalo, Diana; Zapata, María Isabel; Reyes, César; Suárez, Carlos F.; Agudelo, William; Zapata, Wildeman
• Tipo de recurso: Article of investigation
• Fecha de publicación: 2022
• Institución: Universidad de Ciencias Aplicadas y Ambientales U.D.C.A
• Repositorio: Repositorio Institucional UDCA
• Idioma: eng
• OAI Identifier: oai:repository.udca.edu.co:11158/4811
• Acceso en línea: https://repository.udca.edu.co/handle/11158/4811
• Palabra clave: Péptidos sintéticos; Coronavirus del síndrome respiratorio agudo grave 2; Variantes
• Rights: openAccess
• License: https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode.es