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.