Transgenic papaya: a useful platform for oral vaccines
Por:
Fragoso G., Hernández M., Cervantes-Torres J., Ramírez-Aquino R., Chapula H., Villalobos N., Segura-Velázquez R., Figueroa A., Flores I., Jiménez H., Adalid L., Rosas G., Galvez L., Pezzat E., Monreal-Escalante E., Rosales-Mendoza S., Vazquez L.G., Sciutto E.
Publicada:
1 may 2017
Resumen:
Main conclusion Transgenic papaya callus lines expressing the components
of the S3Pvac vaccine constitute a stable platform to produce an oral
vaccine against cysticercosis caused by Taenia solium or T. crassiceps.
The development of effective delivery systems to cope with the reduced
immunogenicity of new subunit vaccines is a priority in vaccinology.
Herein, experimental evidence supporting a papaya-based platform to
produce needle-free, recombinant, highly immunogenic vaccines is shown.
Papaya (Carica papaya) callus lines were previously engineered by
particle bombardment to express the three protective peptides of the
S3Pvac anti-cysticercosis vaccine (KETc7, KETc12, KETc1). Calli were
propagated in vitro, and a stable integration and expression of the
target genes has been maintained, as confirmed by PCR, qRT-PCR, and
HPLC. These results point papaya calli as a suitable platform for
long-term transgenic expression of the vaccine peptides. The previously
demonstrated protective immunogenic efficacy of S3Pvac-papaya orally
administered to mice is herein confirmed in a wider dose-range and
formulated with different delivery vehicles, adequate for oral
vaccination. This protection is accompanied by an increase in
anti-S3Pvac antibody titers and a delayed hypersensitivity response
against the vaccine. A significant increase in CD4+ and CD8+ lymphocyte
proliferation was induced in vitro by each vaccine peptide in mice
immunized with the lowest dose of S3Pvac papaya (0.56 ng of the three
peptides in 0.1 A mu g of papaya callus total protein per mouse). In
pigs, the obliged intermediate host for Taenia solium, S3Pvac papaya was
also immunogenic when orally administered in a two-log dose range.
Vaccinated pigs significantly increased anti-vaccine antibodies and
mononuclear cell proliferation. Overall, the oral immunogenicity of this
stable S3Pvac-papaya vaccine in mice and pigs, not requiring additional
adjuvants, supports the interest in papaya callus as a useful platform
for plant-based vaccines.
Filiaciones:
Fragoso G.:
Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Av. Universidad 3000, Mexico City, CP 04510, Mexico
Hernández M.:
Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Av. Universidad 3000, Mexico City, CP 04510, Mexico
Cervantes-Torres J.:
Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Av. Universidad 3000, Mexico City, CP 04510, Mexico
Ramírez-Aquino R.:
Facultad de Medicina, Benemérita Universidad Autónoma de Puebla, Calle 13 Sur 2702, Puebla, CP 72420, Mexico
Chapula H.:
Facultad de Medicina Veterinaria y Zootecnia, Universidad Nacional Autónoma de México, Av. Universidad 3000, Mexico City, CP 04510, Mexico
Villalobos N.:
Facultad de Medicina Veterinaria y Zootecnia, Universidad Nacional Autónoma de México, Av. Universidad 3000, Mexico City, CP 04510, Mexico
Segura-Velázquez R.:
Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Av. Universidad 3000, Mexico City, CP 04510, Mexico
Figueroa A.:
Unidad Académica de Ciencias Químico Biológicas, Universidad Autónoma de Guerrero, Av. Lázaro Cárdenas s/n, Chilpancingo, GRO CP 39087, Mexico
Flores I.:
Facultad de Ciencias Agropecuarias, Universidad Autónoma del Estado de Morelos, Av. Universidad 1001, Cuernavaca, MOR CP 62209, Mexico
Jiménez H.:
Facultad de Medicina, Benemérita Universidad Autónoma de Puebla, Calle 13 Sur 2702, Puebla, CP 72420, Mexico
Adalid L.:
Instituto Nacional de Neurología y Neurocirugía, SSA, Colonia la Fama, Delegación Tlalpan, Mexico, DF, Mexico
Rosas G.:
Facultad de Medicina, Universidad Autónoma del Estado de Morelos, Av. Universidad 1001, Cuernavaca, MOR CP 62209, Mexico
Galvez L.:
Facultad de Medicina, Benemérita Universidad Autónoma de Puebla, Calle 13 Sur 2702, Puebla, CP 72420, Mexico
Pezzat E.:
Facultad de Medicina, Benemérita Universidad Autónoma de Puebla, Calle 13 Sur 2702, Puebla, CP 72420, Mexico
Monreal-Escalante E.:
Laboratorio de Biofarmacéuticos Recombinantes, Facultad de Ciencias Químicas, Universidad Autónoma de San Luis Potosí, Av. Dr. Manuel Nava 6, San Luis Potosí, 78210, Mexico
Rosales-Mendoza S.:
Laboratorio de Biofarmacéuticos Recombinantes, Facultad de Ciencias Químicas, Universidad Autónoma de San Luis Potosí, Av. Dr. Manuel Nava 6, San Luis Potosí, 78210, Mexico
Vazquez L.G.:
Facultad de Medicina, Benemérita Universidad Autónoma de Puebla, Calle 13 Sur 2702, Puebla, CP 72420, Mexico
Sciutto E.:
Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Av. Universidad 3000, Mexico City, CP 04510, Mexico
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