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1
A novel adjuvant formulation induces robust Th1/Th17 memory and mucosal recall responses in Non-Human Primates.一种新型佐剂制剂在非人灵长类动物中诱导出强大的Th1/Th17记忆和黏膜回忆反应。
bioRxiv. 2023 Feb 23:2023.02.23.529651. doi: 10.1101/2023.02.23.529651.
2
MINCLE and TLR9 agonists synergize to induce Th1/Th17 vaccine memory and mucosal recall in mice and non-human primates.MINCLE 和 TLR9 激动剂协同诱导小鼠和非人灵长类动物产生 Th1/Th17 疫苗记忆和黏膜回忆。
Nat Commun. 2024 Oct 17;15(1):8959. doi: 10.1038/s41467-024-52863-9.
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Method of manufacturing CAF®09 liposomes affects immune responses induced by adjuvanted subunit proteins.CAF®09 脂质体的制造方法会影响佐剂亚单位蛋白诱导的免疫应答。
Eur J Pharm Biopharm. 2023 Aug;189:84-97. doi: 10.1016/j.ejpb.2023.04.005. Epub 2023 Apr 13.
4
Immunomodulation of TH2 biased immunity with mucosal administration of nanoemulsion adjuvant.通过纳米乳剂佐剂的黏膜给药对TH2偏向性免疫进行免疫调节。
Vaccine. 2016 Jul 25;34(34):4017-24. doi: 10.1016/j.vaccine.2016.06.043. Epub 2016 Jun 23.
5
Adsorption of protein antigen to the cationic liposome adjuvant CAF®01 is required for induction of Th1 and Th17 responses but not for antibody induction.蛋白抗原吸附到阳离子脂质体佐剂 CAF®01 上是诱导 Th1 和 Th17 反应所必需的,但不是诱导抗体所必需的。
Eur J Pharm Biopharm. 2021 Aug;165:293-305. doi: 10.1016/j.ejpb.2021.05.020. Epub 2021 May 24.
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Prophylactic Herpes Simplex Virus 2 (HSV-2) Vaccines Adjuvanted with Stable Emulsion and Toll-Like Receptor 9 Agonist Induce a Robust HSV-2-Specific Cell-Mediated Immune Response, Protect against Symptomatic Disease, and Reduce the Latent Viral Reservoir.佐以稳定乳剂和Toll样受体9激动剂的预防性单纯疱疹病毒2型(HSV-2)疫苗可诱导强烈的HSV-2特异性细胞介导免疫反应,预防症状性疾病,并减少潜伏病毒库。
J Virol. 2017 Apr 13;91(9). doi: 10.1128/JVI.02257-16. Print 2017 May 1.
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Adjuvanting a Simian Immunodeficiency Virus Vaccine with Toll-Like Receptor Ligands Encapsulated in Nanoparticles Induces Persistent Antibody Responses and Enhanced Protection in TRIM5α Restrictive Macaques.用包裹在纳米颗粒中的Toll样受体配体辅助猿猴免疫缺陷病毒疫苗可诱导持续性抗体反应并增强对TRIM5α限制型猕猴的保护。
J Virol. 2017 Jan 31;91(4). doi: 10.1128/JVI.01844-16. Print 2017 Feb 15.
8
A new adjuvanted nanoparticle-based H1N1 influenza vaccine induced antigen-specific local mucosal and systemic immune responses after administration into the lung.一种新型的基于纳米颗粒佐剂的H1N1流感疫苗在经肺部给药后可诱导抗原特异性的局部黏膜和全身免疫反应。
Vaccine. 2014 May 30;32(26):3216-22. doi: 10.1016/j.vaccine.2014.04.011. Epub 2014 Apr 13.
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Oral vaccination using microdevices to deliver α-GalCer adjuvanted vaccine afford a mucosal immune response.口服给药微器件传递 α-GalCer 佐剂疫苗可诱导黏膜免疫应答。
J Control Release. 2023 Jan;353:134-146. doi: 10.1016/j.jconrel.2022.11.015. Epub 2022 Nov 23.
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CpG in Combination with an Inhibitor of Notch Signaling Suppresses Formalin-Inactivated Respiratory Syncytial Virus-Enhanced Airway Hyperresponsiveness and Inflammation by Inhibiting Th17 Memory Responses and Promoting Tissue-Resident Memory Cells in Lungs.CpG与Notch信号通路抑制剂联合使用,通过抑制Th17记忆反应和促进肺组织驻留记忆细胞,抑制福尔马林灭活的呼吸道合胞病毒增强的气道高反应性和炎症。
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引用本文的文献

1
Rabies vaccination induces a CD4+ TEM and CD4+CD8+ TEMRA TH1 phenotype in dogs.狂犬病疫苗接种可在犬类中诱导出CD4+ 效应记忆T细胞(TEM)和CD4+CD8+ 终末分化记忆T细胞(TEMRA)TH1表型。
PLoS One. 2025 May 12;20(5):e0323823. doi: 10.1371/journal.pone.0323823. eCollection 2025.

一种新型佐剂制剂在非人灵长类动物中诱导出强大的Th1/Th17记忆和黏膜回忆反应。

A novel adjuvant formulation induces robust Th1/Th17 memory and mucosal recall responses in Non-Human Primates.

作者信息

Woodworth Joshua S, Contreras Vanessa, Christensen Dennis, Naninck Thibaut, Kahlaoui Nidhal, Gallouët Anne-Sophie, Langlois Sébastien, Burban Emma, Joly Candie, Gros Wesley, Dereuddre-Bosquet Nathalie, Morin Julie, Olsen Ming Liu, Rosenkrands Ida, Stein Ann-Kathrin, Wood Grith Krøyer, Follmann Frank, Lindenstrøm Thomas, LeGrand Roger, Pedersen Gabriel Kristian, Mortensen Rasmus

机构信息

Department of Infectious Disease Immunology, Statens Serum Institut; Artillerivej 5, 2300 Copenhagen, Denmark.

Université Paris-Saclay, Inserm, CEA, Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB/IDMIT/UMR1184); 92265, Fontenay-aux-Roses & Kremlin Bicêtre, France.

出版信息

bioRxiv. 2023 Feb 23:2023.02.23.529651. doi: 10.1101/2023.02.23.529651.

DOI:10.1101/2023.02.23.529651
PMID:36865310
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9980079/
Abstract

After clean drinking water, vaccination is the most impactful global health intervention. However, development of new vaccines against difficult-to-target diseases is hampered by the lack of diverse adjuvants for human use. Of particular interest, none of the currently available adjuvants induce Th17 cells. Here, we develop and test an improved liposomal adjuvant, termed CAF10b, that incorporates a TLR-9 agonist. In a head-to-head study in non-human primates (NHPs), immunization with antigen adjuvanted with CAF10b induced significantly increased antibody and cellular immune responses compared to previous CAF adjuvants, already in clinical trials. This was not seen in the mouse model, demonstrating that adjuvant effects can be highly species specific. Importantly, intramuscular immunization of NHPs with CAF10b induced robust Th17 responses that were observed in circulation half a year after vaccination. Furthermore, subsequent instillation of unadjuvanted antigen into the skin and lungs of these memory animals led to significant recall responses including transient local lung inflammation observed by Positron Emission Tomography-Computed Tomography (PET-CT), elevated antibody titers, and expanded systemic and local Th1 and Th17 responses, including >20% antigen-specific T cells in the bronchoalveolar lavage. Overall, CAF10b demonstrated an adjuvant able to drive true memory antibody, Th1 and Th17 vaccine-responses across rodent and primate species, supporting its translational potential.

摘要

除清洁饮用水外,疫苗接种是最具影响力的全球卫生干预措施。然而,针对难以攻克的疾病研发新型疫苗受到了缺乏适用于人类的多种佐剂的阻碍。特别值得关注的是,目前可用的佐剂均不能诱导Th17细胞。在此,我们研发并测试了一种改良的脂质体佐剂,称为CAF10b,它包含一种TLR-9激动剂。在一项针对非人类灵长类动物(NHP)的直接比较研究中,与已进入临床试验阶段的先前CAF佐剂相比,用CAF10b佐剂的抗原进行免疫接种可显著增强抗体和细胞免疫反应。在小鼠模型中未观察到这种情况,这表明佐剂效应可能具有高度的物种特异性。重要的是,用CAF10b对NHP进行肌肉注射免疫可诱导强烈的Th17反应,在接种疫苗半年后仍可在循环系统中观察到。此外,随后将无佐剂抗原滴注到这些记忆动物的皮肤和肺部会引发显著的回忆反应,包括通过正电子发射断层扫描-计算机断层扫描(PET-CT)观察到的短暂局部肺部炎症、抗体滴度升高以及全身和局部Th1及Th17反应增强,包括支气管肺泡灌洗中>20%的抗原特异性T细胞。总体而言,CAF10b证明是一种能够在啮齿动物和灵长类动物物种中驱动真正的记忆抗体、Th1和Th17疫苗反应的佐剂,支持其转化潜力。