Engineered hepatitis B core virus-like particle carrier for precise and personalized Alzheimer's disease vaccine preparation via fixed-point coupling

Heterogenous aggregates of amyloid beta (A beta) and tau protein play a key role in Alzheimer's disease (AD) progression. As the epitope profiles of A beta and abnormally phosphorylated tau change over the course of the disease, tailor immunotherapy to specific patient groups according to the disease stage by targeting corresponding A beta and tau species or both of tau and A beta might improve treatment efficacy. However, epitope peptides have low immunogenicity and peptide vaccine preparation is laborious and time-consuming. We here first constructed a platform for peptide vaccine preparation by inserting SpyCatcher into the major immunodominant region (MIR) of truncated Hepatitis B core protein (HBc)(1-149). The resulted recombinant protein HBc-SpyCatcher (HBc-S) could assemble into uniform and stable virus-like particles (VLPs), and readily bind to the SpyTag conjugated epitope peptides. Several series of peptides such as linear, cyclic and phosphorylated peptides including A beta(1-6), A beta(1-15), cA beta(1-7), cEP1, cEP2 from (beta-amyloid monomer or oligomers, T294, pTau396-404, pTau422 from tau proteins, were glued onto HBc-S VLPs, forming HBc-S-peptide (HBc-S-P) VLPs and efficiently elicited specific Th2-type immune responses. When applied to AD transgenic mice, HBc-S-pTau422 alleviated cognition deficits and neuropathology progression in Tau.P301S transgenic mice. The present study provides an easy, quick, convenient and universal platform for high-throughput peptide epitope screening and personalized peptide vaccine preparation. (C) 2020 Elsevier Ltd. All rights reserved.