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Molecules 2017, 22(11), 1837; doi:10.3390/molecules22111837

A Large Size Chimeric Highly Immunogenic Peptide Presents Multistage Plasmodium Antigens as a Vaccine Candidate System against Malaria

1
Department of Pharmacy, Universidad Nacional de Colombia, Bogotá DC 111321, Colombia
2
Fundación Instituto de Inmunología de Colombia (FIDIC)-Universidad del Rosario, Bogotá DC 111221, Colombia
*
Author to whom correspondence should be addressed.
Received: 20 September 2017 / Revised: 16 October 2017 / Accepted: 23 October 2017 / Published: 1 November 2017
(This article belongs to the Special Issue Peptide Therapeutics)
View Full-Text   |   Download PDF [3964 KB, uploaded 1 November 2017]   |  

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- and 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. View Full-Text
Keywords: Plasmodium; chimeric immunogen; macromolecule synthesis; malaria; vaccine candidate Plasmodium; chimeric immunogen; macromolecule synthesis; malaria; vaccine candidate
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Lozano, J.M.; Varela, Y.; Silva, Y.; Ardila, K.; Forero, M.; Guasca, L.; Guerrero, Y.; Bermudez, A.; Alba, P.; Vanegas, M.; Patarroyo, M.E. A Large Size Chimeric Highly Immunogenic Peptide Presents Multistage Plasmodium Antigens as a Vaccine Candidate System against Malaria. Molecules 2017, 22, 1837.

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