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

ABSTRACT: Fifty ~20–amino acid (aa)–long peptides were selected from functionally relevant SARSCoV-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 b-branched, aromatic aa, short-chain backbone Hbond-forming residues, p-p interactions (n!p* and p-CH), aa interaction with p 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-DRb1* (HLA-DRb1*) 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 HLADRb1* 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: Manuel A., Patarroyo; Patarroyo Murillo, Manuel Elkin; Pabón, Laura; Alba, Martha P; Bermúdez, Adriana; Rugeles López, María Teresa; Díaz Arevalo, Diana; Zapata Builes, Wildeman; Zapata Cardona, María Isabel; Flórez Álvarez, Lizdany; Aguilar Jimenez, Wbeimar; Reyes, César; Suarez, Carlos F; Agudelo, William; López, Carolina; Aza Conde, Jorge; Melo, Miguel; Escamilla, Luis; Oviedo, Jairo; Guzmán, Fanny; Silva, Yolanda; Forero, Martha; Moreno Vranich, Armando; Garry, Jason; Avendaño, Catalina
• Tipo de recurso: Article of investigation
• Fecha de publicación: 2022
• Institución: Universidad de Antioquia
• Repositorio: Repositorio UdeA
• Idioma: eng
• OAI Identifier: oai:bibliotecadigital.udea.edu.co:10495/35481
• Acceso en línea: https://hdl.handle.net/10495/35481
• Palabra clave: SARS-CoV-2; Péptidos; Peptides; Secuencia de Aminoácidos; Amino Acid Sequence; Vacunas contra la COVID-19; COVID-19 Vaccines; Antígenos de Histocompatibilidad Clase II; Histocompatibility Antigens Class II; Antígenos; Antigens; Enfermedades Transmisibles; Communicable Diseases
• Rights: openAccess
• License: https://creativecommons.org/licenses/by/4.0/