Heterogenous aggregates of amyloid β (Aβ) and tau protein play a key role in Alzheimer’s disease (AD) progression. As the epitope profiles of Aβ 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 Aβ and tau species or both of tau and Aβ 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 Aβ(1-6), Aβ(1-15), cAβ(1-7), cEP1, cEP2 from β-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.

淀粉样蛋白β（Aβ）和tau蛋白的异质聚集体在阿尔茨海默病（AD）的进展中起关键作用。由于Aβ的抗原决定簇特征和异常磷酸化的tau在疾病过程中发生变化，通过针对相应的Aβ和tau物种或tau和Aβ两者针对特定的患者群体，根据疾病阶段调整免疫疗法可能会提高治疗效果。然而，表位肽具有低免疫原性，并且肽疫苗的制备费力且费时。我们在这里首先通过将SpyCatcher插入截短的乙型肝炎核心蛋白（HBc）（1-149）的主要免疫优势区（MIR）中，构建了多肽疫苗制备平台。产生的重组蛋白HBc-SpyCatcher（HBc-S）可以组装成均匀且稳定的病毒样颗粒（VLP），并易于与SpyTag缀合的表位肽结合。β-淀粉样单体或寡聚体的几种系列肽，例如线性，环状和磷酸化肽，包括Aβ（1-6），Aβ（1-15），cAβ（1-7），cEP1，cEP2，T294，pTau396-404将来自tau蛋白的pTau422胶粘到HBc-S VLP上，形成HBc-S肽（HBc-SP）VLP，并有效引发特异性Th2型免疫应答。当应用于AD转基因小鼠时，HBc-S-pTau422可减轻Tau.P301S转基因小鼠的认知缺陷和神经病理学进程。本研究为高通量肽表位的筛选和个性化肽疫苗的制备提供了一个简单，快速，方便和通用的平台。将来自β淀粉样单体或寡聚体的cEP2，来自tau蛋白的T294，pTau396-404，pTau422粘在HBc-S VLP上，形成HBc-S肽（HBc-SP）VLP，并有效引发特异性Th2型免疫反应。当应用于AD转基因小鼠时，HBc-S-pTau422可减轻Tau.P301S转基因小鼠的认知缺陷和神经病理学进程。本研究为高通量肽表位的筛选和个性化肽疫苗的制备提供了一个简单，快速，方便和通用的平台。将来自β淀粉样单体或寡聚体的cEP2，来自tau蛋白的T294，pTau396-404，pTau422粘在HBc-S VLP上，形成HBc-S肽（HBc-SP）VLP，并有效引发特异性Th2型免疫反应。当应用于AD转基因小鼠时，HBc-S-pTau422可减轻Tau.P301S转基因小鼠的认知缺陷和神经病理学进程。本研究为高通量肽表位的筛选和个性化肽疫苗的制备提供了一个简单，快速，方便和通用的平台。P301S转基因小鼠。本研究为高通量肽表位的筛选和个性化肽疫苗的制备提供了一个简单，快速，方便和通用的平台。P301S转基因小鼠。本研究为高通量肽表位的筛选和个性化肽疫苗的制备提供了一个简单，快速，方便和通用的平台。