Plant-based chimeric HPV-virus-like particles bearing amyloid-ß epitopes elicit antibodies able to recognize amyloid plaques in APP-tg mouse and Alzheimer’s disease brains
Por:
Gonzalez-Castro, R., Acero Galindo, G., Garcia Salcedo, Y., Uribe Campero, L., Vazquez Perez, V., Carrillo-Tripp, M., Gevorkian, G., Gomez Lim, M. A.
Publicada:
1 jun 2018
Resumen:
The main amyloid-beta (Aß) variants detected in the human brain are full-length Aß1–40 and Aß1–42 peptides; however, a significant proportion of AD brain Aß consists also of N-terminal truncated/modified species. The majority of the previous immunotherapeutic strategies targeted the N-terminal immunodominant epitope of the full-length Aß; however, most of the pathological N-truncated forms of Aß lack this critical B cell epitope. Recently, virus-like particles (VLPs), self-assembled structures with highly ordered repetitive patterns on their surface and capable of inducing robust immune responses, were applied as a promising platform for various antigen expressions. In this study, we expressed in plants two chimeric HPV16 L1 capsid proteins obtained by introduction of the ß-amyloid 11–28 epitope (Aß 11–28) into the h4 helix or into the coil regions of the L1 protein. The Aß 11–28 epitope was chosen because it is present in the full-length Aß 1–42 as well as in the truncated/modified amyloid peptide species. After expression, we assembled the chimerical L1/Aß 11–28 into a VLP in which the Aß 11–28 epitope is exposed at very high density (360 times) on the surface of the VLP. The chimeric VLPs elicited in mice Aß-specific antibodies binding to ß-amyloid plaques in APP-tg mouse and AD brains. Our study is the first to demonstrate a successful production in plants and immunogenic properties in mice of chimeric HPV16 L1 VLPs bearing Aß epitope that may be of potential relevance for the development of multivalent vaccines for a multifactorial disease such as AD. © 2017, Springer International Publishing AG.
Filiaciones:
Gonzalez-Castro, R.:
Centro de Investigación y de Estudios Avanzados del IPN, Unidad Irapuato, Km. 9.6 Libramiento Norte, Carretera Irapuato-León, Irapuato, Guanajuato, Mexico
IPN, Unidad Irapuato, Ctr Invest & Estudios Avanzados, Km 9-6 Libramiento Norte,Carretera Irapuato Leon, Guanajuato 36500, Mexico
Acero Galindo, G.:
Instituto de Investigaciones Biomedicas, Universidad Nacional Autonoma de Mexico (UNAM), Cuidad Universitaria, Apartado Postal 70228, Mexico, DF, Mexico
Univ Nacl Autonoma Mexico, Inst Invest Biomed, Apartado Postal 70228,Cuidad Univ, Mexico City 04510, DF, Mexico
Garcia Salcedo, Y.:
Centro de Investigación y de Estudios Avanzados del IPN, Unidad Irapuato, Km. 9.6 Libramiento Norte, Carretera Irapuato-León, Irapuato, Guanajuato, Mexico
IPN, Unidad Irapuato, Ctr Invest & Estudios Avanzados, Km 9-6 Libramiento Norte,Carretera Irapuato Leon, Guanajuato 36500, Mexico
Uribe Campero, L.:
Centro de Investigación y de Estudios Avanzados del IPN, Unidad Irapuato, Km. 9.6 Libramiento Norte, Carretera Irapuato-León, Irapuato, Guanajuato, Mexico
IPN, Unidad Irapuato, Ctr Invest & Estudios Avanzados, Km 9-6 Libramiento Norte,Carretera Irapuato Leon, Guanajuato 36500, Mexico
Vazquez Perez, V.:
Centro de Investigación y de Estudios Avanzados del IPN, Unidad Irapuato, Km. 9.6 Libramiento Norte, Carretera Irapuato-León, Irapuato, Guanajuato, Mexico
IPN, Unidad Irapuato, Ctr Invest & Estudios Avanzados, Km 9-6 Libramiento Norte,Carretera Irapuato Leon, Guanajuato 36500, Mexico
Carrillo-Tripp, M.:
Centro de Investigación y de Estudios Avanzados del IPN, Unidad Irapuato, Km. 9.6 Libramiento Norte, Carretera Irapuato-León, Irapuato, Guanajuato, Mexico
IPN, Unidad Irapuato, Ctr Invest & Estudios Avanzados, Km 9-6 Libramiento Norte,Carretera Irapuato Leon, Guanajuato 36500, Mexico
Gevorkian, G.:
Instituto de Investigaciones Biomedicas, Universidad Nacional Autonoma de Mexico (UNAM), Cuidad Universitaria, Apartado Postal 70228, Mexico, DF, Mexico
Univ Nacl Autonoma Mexico, Inst Invest Biomed, Apartado Postal 70228,Cuidad Univ, Mexico City 04510, DF, Mexico
Gomez Lim, M. A.:
Centro de Investigación y de Estudios Avanzados del IPN, Unidad Irapuato, Km. 9.6 Libramiento Norte, Carretera Irapuato-León, Irapuato, Guanajuato, Mexico
IPN, Unidad Irapuato, Ctr Invest & Estudios Avanzados, Km 9-6 Libramiento Norte,Carretera Irapuato Leon, Guanajuato 36500, Mexico
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