Plant-based chimeric HPV-virus-like particles bearing amyloid-β epitopes elicit antibodies able to recognize amyloid plaques in APP-tg mouse and Alzheimer’s disease brains
The main amyloid-beta (Aβ) variants detected in the human brain are full-length Aβ1–40 and Aβ1–42 peptides; however, a significant proportion of AD brain Aβ 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 Aβ; however, most of the pathological N-truncated forms of Aβ 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 β-amyloid 11–28 epitope (Aβ 11–28) into the h4 helix or into the coil regions of the L1 protein. The Aβ 11–28 epitope was chosen because it is present in the full-length Aβ 1–42 as well as in the truncated/modified amyloid peptide species. After expression, we assembled the chimerical L1/Aβ 11–28 into a VLP in which the Aβ 11–28 epitope is exposed at very high density (360 times) on the surface of the VLP. The chimeric VLPs elicited in mice Aβ-specific antibodies binding to β-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 Aβ epitope that may be of potential relevance for the development of multivalent vaccines for a multifactorial disease such as AD.
KeywordsAlzheimer disease Virus-like particles Molecular pharming Amyloid-β epitopes Vaccine Antibodies
The authors thank Martin Estrada, Alejandra Aguilar and Diana E. Zavala for excellent technical assistance and Georgina Diaz Herrera for animal care. Funding was provided by DGAPA-UNAM (201116) to G.G.
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