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

doi:10.3390/molecules22111837

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

Título traducido de la contribución: Un péptido quimérico altamente inmunogénico de gran tamaño presenta antígenos de plasmodium multietapa como sistema candidato a vacuna contra la 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

Producción científica: Contribución a una revista › Artículo › revisión exhaustiva

4 Citas (Scopus)

Resumen

Las estrategias racionales para obtener la vacuna contra la malaria deben incluir no sólo una selección adecuada de antígenos diana para la estimulación de anticuerpos, sino también un diseño molecular versátil basado en el ordenamiento de las piezas correctas del complejo rompecabezas molecular del patógeno hacia inmunógenos más activos y funcionales. Los antígenos clásicos de Plasmodium falciparum considerados como candidatos para la vacuna han sido seleccionados como blancos modelo en este estudio. Entre todas las posibilidades hemos elegido epítopos de PfCSP, STARP; MSA1 y Pf155/RESA de etapas pre y eritrocitarias respectivamente para diseñar un gran inmunógeno quimérico de 82 residuos. Se evaluaron varias opciones destinadas a disminuir los obstáculos estéricos para los procedimientos sintéticos sobre la base de la química Fmoc estándar, como la ligadura ortogonal de bloques de construcción; procedimientos asistidos por pseudoprolina y microondas, por lo que el objetivo quimérico grande se produjo, caracterizó y probó inmunológicamente. Las pruebas de antigenicidad y eficacia funcional in vivo de las formulaciones de quimeras grandes administradas solas o como mezclas de antígenos han demostrado la estimulación de títulos de anticuerpos altos, mostrando una fuerte correlación con la protección y la eliminación de parásitos de ratones vacunados con BALB/c después de haber sido letalmente desafiados con las cepas de malaria P. berghei-ANKA y P. yoelii 17XL. Además, las características de la estructura en 3D mostradas por la quimera grande animaron a proponer el uso de estas grandes moléculas sintéticas de diseño racional como sistemas confiables de presentación de vacunas.

Título traducido de la contribución	Un péptido quimérico altamente inmunogénico de gran tamaño presenta antígenos de plasmodium multietapa como sistema candidato a vacuna contra la malaria.
Idioma original	Inglés estadounidense
Número de artículo	1837
Páginas (desde-hasta)	1837
Número de páginas	16
Publicación	Molecules
Volumen	22
N.º	11
DOI	https://doi.org/10.3390/molecules22111837 https://doi.org/10.3390/molecules22111837
Estado	Publicada - nov. 22 2017

Áreas temáticas de ASJC Scopus

Química analítica
Química (miscelánea)
Medicina molecular
Ciencias farmacéuticas
Descubrimiento de medicamentos
Química física y teórica
Química orgánica

ODS de las Naciones Unidas

Este resultado contribuye a los siguientes Objetivos de Desarrollo Sostenible

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Lozano, J. M., Varela, Y., Silva, Y., Ardila, K., Forero, M., Guasca, L., Guerrero, Y., Bermudez, A., Alba, P., Vanegas, M., & Patarroyo, M. E. (2017). A Large Size Chimeric Highly Immunogenic Peptide Presents Multistage Plasmodium Antigens as a Vaccine Candidate System against Malaria. Molecules, 22(11), 1837. Artículo 1837. https://doi.org/10.3390/molecules22111837, https://doi.org/10.3390/molecules22111837

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

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.",

author = "Lozano, {Jos{\'e} Manuel} and Yahson Varela and Yolanda Silva and Karen Ardila and Martha Forero and Laura Guasca and Yuly Guerrero and Adriana Bermudez and Patricia Alba and Magnolia Vanegas and Patarroyo, {Manuel Elkin}",

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Lozano, JM, Varela, Y, Silva, Y, Ardila, K, Forero, M, Guasca, L, Guerrero, Y, Bermudez, A, Alba, P, Vanegas, M & Patarroyo, ME 2017, 'A Large Size Chimeric Highly Immunogenic Peptide Presents Multistage Plasmodium Antigens as a Vaccine Candidate System against Malaria', Molecules, vol. 22, n.º 11, 1837, pp. 1837. https://doi.org/10.3390/molecules22111837, https://doi.org/10.3390/molecules22111837

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AU - Lozano, José Manuel

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AU - Ardila, Karen

AU - Forero, Martha

AU - Guasca, Laura

AU - Guerrero, Yuly

AU - Bermudez, Adriana

AU - Alba, Patricia

AU - Vanegas, Magnolia

AU - Patarroyo, Manuel Elkin

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N2 - 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.

AB - 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.

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

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ODS de las Naciones Unidas

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