Suppr超能文献

一种能够增强多糖抗原保护性抗体反应并引发回忆反应的佐剂。

An Adjuvant That Increases Protective Antibody Responses to Polysaccharide Antigens and Enables Recall Responses.

机构信息

Department of Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, North Carolina.

出版信息

J Infect Dis. 2019 Jan 7;219(2):323-334. doi: 10.1093/infdis/jiy506.

Abstract

Protection against encapsulated bacteria can be elicited using polysaccharide vaccines. These antigens often behave as T-cell-independent type 2 antigens (TI-2 Ags). However, TI-2 Ags, including pneumococcal polysaccharides, often elicit weak immunoglobulin G (IgG) responses and are refractive to boosting. Conjugate vaccines have not completely overcome this challenge and hence, alternative strategies are required to enhance polysaccharide vaccine responses. Herein, we describe an adjuvant consisting of a Toll-like receptor and C-type lectin receptor agonist pairing that significantly increases primary immunoglobulin M and IgG responses to TI-2 Ags as well as enables significant boosting when coadministered with polysaccharide vaccines. Consistent with this, the adjuvant significantly increased the generation of both TI-2 memory B cells and long-lived antibody secreting cells. Adjuvant effects were highly dependent on B-cell-intrinsic MyD88, but not Trif expression. Importantly, coadministration of the adjuvant with the Pneumovax vaccine significantly increased the protective efficacy of vaccination in a lethal challenge mouse model of pneumococcal respiratory infection. Collectively, these data provide evidence that B-cell-directed adjuvants have promise in significantly improving the quality and quantity of serologic and B-cell memory responses to clinically relevant polysaccharide vaccines.

摘要

针对囊膜细菌的保护作用可以通过多糖疫苗来诱导。这些抗原通常表现为 T 细胞非依赖性 2 型抗原(TI-2 抗原)。然而,包括肺炎球菌多糖在内的 TI-2 抗原通常会引起较弱的免疫球蛋白 G(IgG)反应,并且对增强反应具有抵抗力。结合疫苗并未完全克服这一挑战,因此需要采用替代策略来增强多糖疫苗的反应。在此,我们描述了一种佐剂,由 Toll 样受体和 C 型凝集素受体激动剂配对组成,该佐剂可显著提高 TI-2 抗原的初次免疫球蛋白 M 和 IgG 反应,并在与多糖疫苗共同给药时实现显著增强。与之一致的是,该佐剂显著增加了 TI-2 记忆 B 细胞和长寿抗体分泌细胞的产生。佐剂作用高度依赖于 B 细胞内在的 MyD88,但不依赖于 Trif 表达。重要的是,佐剂与 Pneumovax 疫苗共同给药可显著提高肺炎球菌呼吸道感染致死性挑战小鼠模型中疫苗接种的保护效力。总之,这些数据提供了证据,表明针对 B 细胞的佐剂有望显著提高临床相关多糖疫苗的血清学和 B 细胞记忆反应的质量和数量。

相似文献

6
Compound 48/80 acts as a potent mucosal adjuvant for vaccination against Streptococcus pneumoniae infection in young mice.
Vaccine. 2015 Feb 18;33(8):1008-16. doi: 10.1016/j.vaccine.2015.01.013. Epub 2015 Jan 14.
8
Mucosal vaccination against encapsulated respiratory bacteria--new potentials for conjugate vaccines?
Scand J Immunol. 2003 Aug;58(2):119-28. doi: 10.1046/j.1365-3083.2003.01292.x.

引用本文的文献

1
Distinct effects of adjuvants on B cell responses to protein or polysaccharide antigens contained in glycoconjugate vaccines.
Front Immunol. 2025 Aug 22;16:1574941. doi: 10.3389/fimmu.2025.1574941. eCollection 2025.
2
B cell-expressed CD1d promotes MPL/TDCM lipid emulsion adjuvant effects in polysaccharide vaccines.
J Immunol. 2025 Jul 1;214(7):1630-1642. doi: 10.1093/jimmun/vkaf074.
3
Recent Advances in the Development of Mincle-Targeting Vaccine Adjuvants.
Vaccines (Basel). 2024 Nov 26;12(12):1320. doi: 10.3390/vaccines12121320.
4
A TLR4 ligand-based adjuvant for promoting the immunogenicity of typhoid subunit vaccines.
Front Immunol. 2024 May 10;15:1383476. doi: 10.3389/fimmu.2024.1383476. eCollection 2024.
5
TLR4 Ligands in Typhoid Vi Polysaccharide Subunit Vaccines Contribute to Immunogenicity.
Immunohorizons. 2024 Jan 1;8(1):29-34. doi: 10.4049/immunohorizons.2300085.
6
Type I IFN Receptor Signaling on B Cells Promotes Antibody Responses to Polysaccharide Antigens.
J Immunol. 2023 Jan 15;210(2):148-157. doi: 10.4049/jimmunol.2200538.
7
Vaccination of older adults: Influenza, pneumococcal disease, herpes zoster, COVID-19 and beyond.
Immun Ageing. 2021 Oct 9;18(1):38. doi: 10.1186/s12979-021-00249-6.
8
The PD-1 Regulatory Axis Inhibits T Cell-Independent B Cell Memory Generation and Reactivation.
J Immunol. 2021 Oct 15;207(8):1978-1989. doi: 10.4049/jimmunol.2100336. Epub 2021 Sep 17.
9
An Overview of Nanocarrier-Based Adjuvants for Vaccine Delivery.
Pharmaceutics. 2021 Mar 27;13(4):455. doi: 10.3390/pharmaceutics13040455.
10
B Cell Subsets Differentially Contribute to the T Cell-Independent Memory Pool.
J Immunol. 2020 Nov 1;205(9):2362-2374. doi: 10.4049/jimmunol.1901453. Epub 2020 Sep 25.

本文引用的文献

1
PD-L2 Regulates B-1 Cell Antibody Production against Phosphorylcholine through an IL-5-Dependent Mechanism.
J Immunol. 2017 Sep 15;199(6):2020-2029. doi: 10.4049/jimmunol.1700555. Epub 2017 Aug 2.
2
Typhi Porins OmpC and OmpF Are Potent Adjuvants for T-Dependent and T-Independent Antigens.
Front Immunol. 2017 Mar 9;8:230. doi: 10.3389/fimmu.2017.00230. eCollection 2017.
3
Why the recent ACIP recommendations regarding conjugate pneumococcal vaccine in adults may be irrelevant.
Hum Vaccin Immunother. 2016;12(2):331-5. doi: 10.1080/21645515.2015.1098794.
4
PD-1 suppresses protective immunity to Streptococcus pneumoniae through a B cell-intrinsic mechanism.
J Immunol. 2015 Mar 1;194(5):2289-99. doi: 10.4049/jimmunol.1401673. Epub 2015 Jan 26.
9
The Mincle-activating adjuvant TDB induces MyD88-dependent Th1 and Th17 responses through IL-1R signaling.
PLoS One. 2013;8(1):e53531. doi: 10.1371/journal.pone.0053531. Epub 2013 Jan 7.
10
Effects of Differences in Lipid A Structure on TLR4 Pro-Inflammatory Signaling and Inflammasome Activation.
Front Immunol. 2012 Jun 13;3:154. doi: 10.3389/fimmu.2012.00154. eCollection 2012.

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验