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基于MultiTEP平台技术的Tau疫苗在非人灵长类动物中的免疫原性。

Immunogenicity of MultiTEP platform technology-based Tau vaccine in non-human primates.

作者信息

Hovakimyan Armine, Zagorski Karen, Chailyan Gor, Antonyan Tatevik, Melikyan Levon, Petrushina Irina, Batt Dash G, King Olga, Ghazaryan Manush, Donthi Aashrit, Foose Caitlynn, Petrovsky Nikolai, Cribbs David H, Agadjanyan Michael G, Ghochikyan Anahit

机构信息

Department of Molecular Immunology, Institute for Molecular Medicine, Huntington Beach, CA, USA.

Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA, USA.

出版信息

NPJ Vaccines. 2022 Oct 12;7(1):117. doi: 10.1038/s41541-022-00544-3.

DOI:10.1038/s41541-022-00544-3
PMID:36224191
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9556597/
Abstract

Pathological forms of Tau protein are directly associated with neurodegeneration and correlate with Alzheimer's Disease (AD) symptoms, progression, and severity. Previously, using various mouse models of Tauopathies and AD, we have demonstrated the immunogenicity and efficacy of the MultiTEP-based adjuvanted vaccine targeting the phosphatase activating domain (PAD) of Tau, AV-1980R/A. Here, we analyzed its immunogenicity in non-human primates (NHP), the closest phylogenic relatives to humans with a similar immune system, to initiate the transition of this vaccine into clinical trials. We have demonstrated that AV-1980R/A is highly immunogenic in these NHPs, activating a broad but unique to each monkey repertoire of MultiTEP-specific T helper (Th) cells that, in turn, activate B cells specific to PAD. The resulting anti-PAD IgG antibodies recognize pathological Tau tangles and Tau-positive neuritis in AD case brain sections with no staining in control non-AD cases. These published data and efficacy results support the AV-1980R/A vaccine progression to first-in-human clinical trials.

摘要

Tau蛋白的病理形式与神经退行性变直接相关，并与阿尔茨海默病（AD）的症状、进展和严重程度相关。此前，我们使用多种Tau蛋白病和AD的小鼠模型，证明了靶向Tau蛋白磷酸酶激活域（PAD）的基于MultiTEP的佐剂疫苗AV-1980R/A的免疫原性和有效性。在此，我们分析了其在非人灵长类动物（NHP）中的免疫原性，NHP是与人类亲缘关系最近且免疫系统相似的动物，以启动该疫苗向临床试验的转化。我们证明，AV-1980R/A在这些NHP中具有高度免疫原性，可激活广泛但对每只猴子而言独特的MultiTEP特异性辅助性T（Th）细胞库，进而激活针对PAD的特异性B细胞。由此产生的抗PAD IgG抗体可识别AD病例脑切片中的病理性Tau缠结和Tau阳性神经炎，而在对照非AD病例中无染色。这些已发表的数据和有效性结果支持AV-1980R/A疫苗进入首次人体临床试验。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/803f/9556597/74a89dc993c5/41541_2022_544_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/803f/9556597/d9f6781c021f/41541_2022_544_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/803f/9556597/3553966dd6e1/41541_2022_544_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/803f/9556597/dc5e0350ab05/41541_2022_544_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/803f/9556597/ee43229633d8/41541_2022_544_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/803f/9556597/26c26eadb115/41541_2022_544_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/803f/9556597/74a89dc993c5/41541_2022_544_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/803f/9556597/d9f6781c021f/41541_2022_544_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/803f/9556597/3553966dd6e1/41541_2022_544_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/803f/9556597/dc5e0350ab05/41541_2022_544_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/803f/9556597/ee43229633d8/41541_2022_544_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/803f/9556597/26c26eadb115/41541_2022_544_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/803f/9556597/74a89dc993c5/41541_2022_544_Fig6_HTML.jpg

相似文献

[1]
Immunogenicity of MultiTEP platform technology-based Tau vaccine in non-human primates.

NPJ Vaccines. 2022-10-12

[2]
Alzheimer's disease Advax(CpG)- adjuvanted MultiTEP-based dual and single vaccines induce high-titer antibodies against various forms of tau and Aβ pathological molecules.

Sci Rep. 2016-7-1

[3]
A MultiTEP platform-based epitope vaccine targeting the phosphatase activating domain (PAD) of tau: therapeutic efficacy in PS19 mice.

Sci Rep. 2019-10-29

[4]
Active immunization with tau epitope in a mouse model of tauopathy induced strong antibody response together with improvement in short memory and pSer396-tau pathology.

Neurobiol Dis. 2020-2

[5]
Testing a MultiTEP-based combination vaccine to reduce Aβ and tau pathology in Tau22/5xFAD bigenic mice.

Alzheimers Res Ther. 2019-12-17

[6]
MultiTEP platform-based DNA epitope vaccine targeting N-terminus of tau induces strong immune responses and reduces tau pathology in THY-Tau22 mice.

Vaccine. 2017-4-11

[7]
The MultiTEP platform-based Alzheimer's disease epitope vaccine activates a broad repertoire of T helper cells in nonhuman primates.

Alzheimers Dement. 2014-2-20

[8]
MultiTEP platform-based DNA vaccines for alpha-synucleinopathies: preclinical evaluation of immunogenicity and therapeutic potency.

Neurobiol Aging. 2017-11

[9]
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Vaccines (Basel). 2024-6-14

[10]
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Neurobiol Dis. 2016-10

引用本文的文献

[1]
mRNA Vaccine for Alzheimer's Disease: Pilot Study.

Vaccines (Basel). 2024-6-14

[2]
Alzheimer's disease and its treatment-yesterday, today, and tomorrow.

Front Pharmacol. 2024-5-24

[3]
Inflammation, Autoimmunity and Neurodegenerative Diseases, Therapeutics and Beyond.

Curr Neuropharmacol. 2024

[4]
Advax-CpG55.2-adjuvanted monovalent or trivalent SARS-CoV-2 recombinant spike protein vaccine protects hamsters against heterologous infection with Beta or Delta variants.

Vaccine. 2023-11-22

[5]
Therapies for Tau-associated neurodegenerative disorders: targeting molecules, synapses, and cells.

Neural Regen Res. 2023-12

[6]
Novel Vaccine against Pathological Pyroglutamate-Modified Amyloid Beta for Prevention of Alzheimer's Disease.

Int J Mol Sci. 2023-6-6

本文引用的文献

[1]
ADAMANT: a placebo-controlled randomized phase 2 study of AADvac1, an active immunotherapy against pathological tau in Alzheimer's disease.

Nat Aging. 2021-6

[2]
Efficacy and immunogenicity of MultiTEP-based DNA vaccines targeting human α-synuclein: prelude for IND enabling studies.

NPJ Vaccines. 2022-1-10

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Drugs Context. 2021-10-4

[4]
Can we learn lessons from the FDA's approval of aducanumab?

Nat Rev Neurol. 2021-11

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A truncated glycoprotein G vaccine formulated with Advax-CpG adjuvant provides protection of mice against genital herpes simplex virus 2 infection.

Vaccine. 2021-9-24

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Safety and efficacy of anti-tau monoclonal antibody gosuranemab in progressive supranuclear palsy: a phase 2, randomized, placebo-controlled trial.

Nat Med. 2021-8

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Antibody semorinemab reduces tau pathology in a transgenic mouse model and engages tau in patients with Alzheimer's disease.

Sci Transl Med. 2021-5-12

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Advax-CpG Adjuvant Provides Antigen Dose-Sparing and Enhanced Immunogenicity for Inactivated Poliomyelitis Virus Vaccines.

Pathogens. 2021-4-21

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New Insights Into Drug Discovery Targeting Tau Protein.

Front Mol Neurosci. 2020-12-3

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Alzheimers Dement. 2021-4

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