Stimulation Effects and Mechanisms of Different Adjuvants on a Norovirus P Particle-Based Active Amyloid-β Vaccine

免疫原性 佐剂 免疫系统 抗原 表位 生物 免疫学 病毒学 医学
作者
Mingrui Dai,Xuejian Feng,Zengshuo Mo,Yao Sun,Lu Fu,Yong Zhang,Jiaxin Wu,Bin Yu,Haihong Zhang,Xianghui Yu,Hui Wu,Wei Kong
出处
期刊:Journal of Alzheimer's Disease [IOS Press]
卷期号:77 (4): 1717-1732 被引量:1
标识
DOI:10.3233/jad-200351
摘要

Background: Adjuvants are important components of vaccines and effectively enhance the immune response of specific antigens. However, the role of adjuvants or combinations of adjuvants in stimulating immunogenicity of the amyloid-β (Aβ) vaccine, as well as molecular mechanisms underlying such stimulation still remain unclear. A previous study of ours developed a norovirus P particle-based active Aβ epitope vaccine, PP-3copy-Aβ1-6-loop123, which stimulates a high titer of Aβ-specific antibodies in mouse Alzheimer’s disease (AD) models. Objective: The most effective and safe adjuvant that maximizes the immunogenicity of our protein vaccine was determined. Methods: We investigated four adjuvants (CpG, AS02, AS03, and MF59), and combinations of those, for capacity to enhance immunogenicity, and performed transcriptome analysis to explore mechanisms underlying the role of these in AD immunotherapy. Results: Addition of the adjuvant, AS02, remarkably improved the immunogenicity of the PP-3copy-Aβ1-6-loop123 vaccine without triggering an Aβ-specific T-cell response. Combinations of adjuvants, particularly CpG + AS02 and CpG + AS03, elicited a significantly elevated and prolonged Aβ-specific antibody response. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses indicated that a combination of two adjuvants was more effective in activating immune-related pathways, thereby enhancing the immunogenicity of PP-3copy-Aβ1-6-loop123. Conclusion: These findings demonstrated that adjuvants can be used as enhancers in AD protein vaccination, and that a combination of CpG and AS-related adjuvants may be a very effective adjuvant candidate suitable for further clinical trials of the PP-3copy-Aβ1-6-loop123 vaccine. Our studies also revealed potential mechanisms underlying the stimulation of immune response of protein vaccines by adjuvants.
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