A large size chimeric highly immunogenic peptide presents multistage plasmodium antigens as a vaccine candidate system against malaria

José Manuel Lozano, Yahson Varela, Yolanda Silva, Karen Ardila, Martha Forero, Laura Guasca, Yuly Guerrero, Adriana Bermudez, Patricia Alba, Magnolia Vanegas, Manuel Elkin Patarroyo

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Rational strategies for obtaining malaria vaccine candidates should include not only a proper selection of target antigens for antibody stimulation, but also a versatile molecular design based on ordering the right pieces from the complex pathogen molecular puzzle towards more active and functional immunogens. Classical Plasmodium falciparum antigens regarded as vaccine candidates have been selected as model targets in this study. Among all possibilities we have chosen epitopes of PfCSP, STARP; MSA1 and Pf155/RESA from pre- A nd erythrocyte stages respectively for designing a large 82-residue chimeric immunogen. A number of options aimed at diminishing steric hindrance for synthetic procedures were assessed based on standard Fmoc chemistry such as building block orthogonal ligation; pseudo-proline and microwave-assisted procedures, therefore the large-chimeric target was produced, characterized and immunologically tested. Antigenicity and functional in vivo efficacy tests of the large-chimera formulations administered alone or as antigen mixtures have proven the stimulation of high antibody titers, showing strong correlation with protection and parasite clearance of vaccinated BALB/c mice after being lethally challenged with both P. berghei-ANKA and P. yoelii 17XL malaria strains. Besides, 3D structure features shown by the large-chimera encouraged as to propose using these rational designed large synthetic molecules as reliable vaccine candidate-presenting systems.

Translated title of the contributionUn péptido quimérico altamente inmunogénico de gran tamaño presenta antígenos de plasmodium multietapa como sistema candidato a vacuna contra la malaria.
Original languageEnglish (US)
Article number1837
Pages (from-to)1837
Number of pages16
JournalMolecules
Volume22
Issue number11
DOIs
StatePublished - Nov 22 2017

All Science Journal Classification (ASJC) codes

  • Analytical Chemistry
  • Chemistry (miscellaneous)
  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery
  • Physical and Theoretical Chemistry
  • Organic Chemistry

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