• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

Toll样受体3佐剂与病毒样颗粒联合使用可引发针对HIV的体液免疫反应。

Toll-like receptor 3 adjuvant in combination with virus-like particles elicit a humoral response against HIV.

作者信息

Poteet Ethan, Lewis Phoebe, Chen Changyi, Ho Sam On, Do Thai, Chiang SuMing, Labranche Celia, Montefiori David, Fujii Gary, Yao Qizhi

机构信息

Michael E. DeBakey Department of Surgery, Division of Surgical Research, Baylor College of Medicine, Houston, TX 77030, USA.

Molecular Express, Inc., Rancho Domínguez, CA 90220, USA.

出版信息

Vaccine. 2016 Nov 21;34(48):5886-5894. doi: 10.1016/j.vaccine.2016.10.036. Epub 2016 Oct 27.

DOI:10.1016/j.vaccine.2016.10.036
PMID:27997339
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8370845/
Abstract

Human Immunodeficiency Virus (HIV) Virus-Like Particles (VLPs) composed of HIV Gag and HIV gp120/gp41 envelope are a pseudovirion vaccine capable of presenting antigens in their native conformations. To enhance the immunogenicity of the HIV Env antigen, VLPs were coupled to VesiVax Conjugatable Adjuvant Lipid Vesicles (CALV) containing one of four toll-like-receptor (TLR) ligands, each activating a receptor with distinct cellular localization and downstream pathways. C57BL/6 mice were vaccinated by intranasal prime followed by two sub-cheek boosts and their sera immunoglobulin and neutralizing potency were measured over a duration of 3months after vaccination. PBS control, VLPs alone, CALV+VLPs, and VLPs complexed with CALV and ligands for TLR2 (PAM3CAG), TLR3 (dsRNA), TLR4 (MPLA), or TLR7/8 (resiquimod) were evaluated based on antibody titer, IgG1 and IgG2c class switching, germinal center formation, T follicular cells and potency of neutralizing antibodies. Consistently, the TLR3 ligand dsRNA complexed to CALV and in combination with VLPs (CALV(dsRNA)+VLPs) induced the strongest response. CALV(dsRNA)+VLPs induced the highest titers against the recombinant vaccine antigens clade B Bal gp120 and pr55 Gag. Additionally, CALV(dsRNA)+VLPs induced cross-clade antibodies, represented by high titers of antibody to clade c 96ZM651 gp120. CALV(dsRNA)+VLPs induced predominantly IgG2c over IgG1, a response associated with T helper type 1 (Th1)-like cytokines. In turn, CALV(dsRNA)+VLP immunized mice generated the most potent neutralizing antibodies against HIV strain MN.3. Finally, at time of sacrifice, a significant increase in germinal center B cells and T follicular cells was detected in mice which received CALV(dsRNA)+VLPs compared to PBS. Our results indicate that CALV(dsRNA) is a superior adjuvant for HIV VLPs in generating a Th1-like immunoglobulin profile, while prolonging lymph node germinal centers, T follicular cells and generating neutralizing antibodies to a highly sensitive tier 1A variant of HIV.

摘要

由HIV Gag和HIV gp120/gp41包膜组成的人类免疫缺陷病毒（HIV）病毒样颗粒（VLP）是一种能够以天然构象呈递抗原的假病毒疫苗。为增强HIV Env抗原的免疫原性，将VLP与包含四种Toll样受体（TLR）配体之一的VesiVax可共轭佐剂脂质囊泡（CALV）偶联，每种配体激活具有不同细胞定位和下游途径的受体。对C57BL/6小鼠进行鼻内初免，随后进行两次颊下加强免疫，并在接种后3个月内测量其血清免疫球蛋白和中和效力。基于抗体滴度、IgG1和IgG2c类别转换、生发中心形成、T滤泡细胞以及中和抗体效力，对PBS对照、单独的VLP、CALV+VLP以及与CALV和TLR2（PAM3CAG）、TLR3（dsRNA）、TLR4（MPLA）或TLR7/8（瑞喹莫德）配体复合的VLP进行了评估。一致的是，与CALV复合并与VLP联合使用的TLR3配体dsRNA（CALV(dsRNA)+VLP）诱导了最强的反应。CALV(dsRNA)+VLP诱导了针对重组疫苗抗原B亚型Bal gp120和pr55 Gag的最高滴度。此外，CALV(dsRNA)+VLP诱导了交叉亚型抗体，以针对C亚型96ZM651 gp120的高滴度抗体为代表。CALV(dsRNA)+VLP主要诱导IgG2c而非IgG1，这是一种与1型辅助性T细胞（Th1）样细胞因子相关的反应。相应地，用CALV(dsRNA)+VLP免疫的小鼠产生了针对HIV毒株MN.3的最有效的中和抗体。最后，在处死时，与PBS相比，在接受CALV(dsRNA)+VLP的小鼠中检测到生发中心B细胞和T滤泡细胞显著增加。我们的结果表明，CALV(dsRNA)是HIV VLP的一种优质佐剂，可产生Th1样免疫球蛋白谱，同时延长淋巴结生发中心、T滤泡细胞，并产生针对HIV高度敏感的1A组变体的中和抗体。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b9f/8370845/5d3a752d620b/nihms-843361-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b9f/8370845/43998ea6b92e/nihms-843361-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b9f/8370845/65877495008f/nihms-843361-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b9f/8370845/2a5c299c61ec/nihms-843361-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b9f/8370845/5d3a752d620b/nihms-843361-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b9f/8370845/43998ea6b92e/nihms-843361-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b9f/8370845/65877495008f/nihms-843361-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b9f/8370845/2a5c299c61ec/nihms-843361-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b9f/8370845/5d3a752d620b/nihms-843361-f0004.jpg

相似文献

1
Toll-like receptor 3 adjuvant in combination with virus-like particles elicit a humoral response against HIV.Toll样受体3佐剂与病毒样颗粒联合使用可引发针对HIV的体液免疫反应。
Vaccine. 2016 Nov 21;34(48):5886-5894. doi: 10.1016/j.vaccine.2016.10.036. Epub 2016 Oct 27.
2
A Novel Prime and Boost Regimen of HIV Virus-Like Particles with TLR4 Adjuvant MPLA Induces Th1 Oriented Immune Responses against HIV.一种新型的含TLR4佐剂MPLA的HIV病毒样颗粒初免-加强方案可诱导针对HIV的Th1型定向免疫反应。
PLoS One. 2015 Aug 27;10(8):e0136862. doi: 10.1371/journal.pone.0136862. eCollection 2015.
3
A Novel MVA-Based HIV Vaccine Candidate (MVA-gp145-GPN) Co-Expressing Clade C Membrane-Bound Trimeric gp145 Env and Gag-Induced Virus-Like Particles (VLPs) Triggered Broad and Multifunctional HIV-1-Specific T Cell and Antibody Responses.一种新型基于 MVA 的 HIV 疫苗候选物（MVA-gp145-GPN），共表达 C 型膜结合三聚体 gp145Env 和 Gag 诱导的病毒样颗粒（VLPs），引发广泛的多功能 HIV-1 特异性 T 细胞和抗体反应。
Viruses. 2019 Feb 16;11(2):160. doi: 10.3390/v11020160.
4
HIV/AIDS Vaccine Candidates Based on Replication-Competent Recombinant Poxvirus NYVAC-C-KC Expressing Trimeric gp140 and Gag-Derived Virus-Like Particles or Lacking the Viral Molecule B19 That Inhibits Type I Interferon Activate Relevant HIV-1-Specific B and T Cell Immune Functions in Nonhuman Primates.基于表达三聚体gp140和Gag衍生病毒样颗粒的复制能力重组痘病毒NYVAC-C-KC或缺乏抑制I型干扰素的病毒分子B19的HIV/AIDS候选疫苗，在非人灵长类动物中激活相关的HIV-1特异性B和T细胞免疫功能。
J Virol. 2017 Apr 13;91(9). doi: 10.1128/JVI.02182-16. Print 2017 May 1.
5
Virus-Like Particles Displaying Trimeric Simian Immunodeficiency Virus (SIV) Envelope gp160 Enhance the Breadth of DNA/Modified Vaccinia Virus Ankara SIV Vaccine-Induced Antibody Responses in Rhesus Macaques.展示三聚体猴免疫缺陷病毒（SIV）包膜糖蛋白160的病毒样颗粒增强了恒河猴中DNA/改良痘苗病毒安卡拉SIV疫苗诱导的抗体反应的广度。
J Virol. 2016 Sep 12;90(19):8842-54. doi: 10.1128/JVI.01163-16. Print 2016 Oct 1.
6
In vivo electroporation in DNA-VLP prime-boost preferentially enhances HIV-1 envelope-specific IgG2a, neutralizing antibody and CD8 T cell responses.在DNA-病毒样颗粒初免-加强免疫中进行体内电穿孔可优先增强HIV-1包膜特异性IgG2a、中和抗体及CD8 T细胞反应。
Vaccine. 2017 Apr 11;35(16):2042-2051. doi: 10.1016/j.vaccine.2017.03.006. Epub 2017 Mar 17.
7
Potent Induction of Envelope-Specific Antibody Responses by Virus-Like Particle Immunogens Based on HIV-1 Envelopes from Patients with Early Broadly Neutralizing Responses.基于具有早期广泛中和反应的患者的 HIV-1 包膜的病毒样颗粒免疫原可有效诱导包膜特异性抗体应答。
J Virol. 2022 Jan 12;96(1):e0134321. doi: 10.1128/JVI.01343-21. Epub 2021 Oct 20.
8
Effect of HIV-1 envelope cytoplasmic tail on adenovirus primed virus encoded virus-like particle immunizations.HIV-1包膜蛋白胞质尾对腺病毒引发的病毒编码病毒样颗粒免疫的影响。
Vaccine. 2016 Oct 17;34(44):5344-5351. doi: 10.1016/j.vaccine.2016.08.089. Epub 2016 Sep 12.
9
Recombinant human immunodeficiency Pr55gag virus-like particles presenting chimeric envelope glycoproteins induce cytotoxic T-cells and neutralizing antibodies.呈现嵌合包膜糖蛋白的重组人免疫缺陷病毒Pr55gag病毒样颗粒可诱导细胞毒性T细胞和中和抗体。
Virology. 1997 Aug 18;235(1):26-39. doi: 10.1006/viro.1997.8668.
10
Development of HIV/AIDS vaccine using chimeric gag-env virus-like particles.利用嵌合gag-env病毒样颗粒开发艾滋病毒/艾滋病疫苗。
Biol Chem. 1999 Mar;380(3):353-64. doi: 10.1515/BC.1999.047.

引用本文的文献

1
Identifying Key Drivers of Efficient B Cell Responses: On the Role of T Help, Antigen-Organization, and Toll-like Receptor Stimulation for Generating a Neutralizing Anti-Dengue Virus Response.确定高效B细胞反应的关键驱动因素：关于T辅助、抗原组织和Toll样受体刺激在产生中和性抗登革病毒反应中的作用
Vaccines (Basel). 2024 Jun 14;12(6):661. doi: 10.3390/vaccines12060661.
2
DC-targeting lentivectors for cancer immunotherapy.用于癌症免疫治疗的靶向树突状细胞慢病毒载体
Immunother Adv. 2023 Nov 1;3(1):ltad023. doi: 10.1093/immadv/ltad023. eCollection 2023.
3
Enhanced T-Cell Priming and Improved Anti-Tumor Immunity through Lymphatic Delivery of Checkpoint Blockade Immunotherapy.

本文引用的文献

1
A Novel Prime and Boost Regimen of HIV Virus-Like Particles with TLR4 Adjuvant MPLA Induces Th1 Oriented Immune Responses against HIV.一种新型的含TLR4佐剂MPLA的HIV病毒样颗粒初免-加强方案可诱导针对HIV的Th1型定向免疫反应。
PLoS One. 2015 Aug 27;10(8):e0136862. doi: 10.1371/journal.pone.0136862. eCollection 2015.
2
Human circulating PD-1+CXCR3-CXCR5+ memory Tfh cells are highly functional and correlate with broadly neutralizing HIV antibody responses.人类循环 PD-1+CXCR3-CXCR5+记忆性滤泡辅助 T 细胞具有高度功能性，与广泛中和 HIV 抗体反应相关。
Immunity. 2013 Oct 17;39(4):758-69. doi: 10.1016/j.immuni.2013.08.031. Epub 2013 Sep 12.
3
通过淋巴途径递送检查点阻断免疫疗法增强T细胞启动并改善抗肿瘤免疫
Cancers (Basel). 2022 Apr 4;14(7):1823. doi: 10.3390/cancers14071823.
4
Innovative vaccine platforms against infectious diseases: Under the scope of the COVID-19 pandemic.创新型传染病疫苗平台：在 COVID-19 大流行背景下。
Int J Pharm. 2021 Dec 15;610:121212. doi: 10.1016/j.ijpharm.2021.121212. Epub 2021 Oct 20.
5
Orthogonal modular biosynthesis of nanoscale conjugate vaccines for vaccination against infection.用于抗感染疫苗接种的纳米级缀合疫苗的正交模块化生物合成。
Nano Res. 2022;15(2):1645-1653. doi: 10.1007/s12274-021-3713-4. Epub 2021 Aug 12.
6
CTLA-4 Blockade, during HIV Virus-Like Particles Immunization, Alters HIV-Specific B-Cell Responses.在HIV病毒样颗粒免疫期间阻断CTLA-4，会改变HIV特异性B细胞反应。
Vaccines (Basel). 2020 Jun 6;8(2):284. doi: 10.3390/vaccines8020284.
7
Recent Advances in Nanovaccines Using Biomimetic Immunomodulatory Materials.使用仿生免疫调节材料的纳米疫苗的最新进展
Pharmaceutics. 2019 Oct 14;11(10):534. doi: 10.3390/pharmaceutics11100534.
8
The differences in immunoadjuvant mechanisms of TLR3 and TLR4 agonists on the level of antigen-presenting cells during immunization with recombinant adenovirus vector.在重组腺病毒载体免疫接种过程中，TLR3 和 TLR4 激动剂在抗原呈递细胞水平上的免疫佐剂机制的差异。
BMC Immunol. 2018 Jul 28;19(1):26. doi: 10.1186/s12865-018-0264-x.
9
Engineering a Rugged Nanoscaffold To Enhance Plug-and-Display Vaccination.工程化坚固纳米支架以增强即插即用型疫苗接种。
ACS Nano. 2018 Sep 25;12(9):8855-8866. doi: 10.1021/acsnano.8b02805. Epub 2018 Jul 26.
10
Viruses Seen by Our Cells: The Role of Viral RNA Sensors.细胞所看到的病毒：病毒 RNA 传感器的作用。
J Immunol Res. 2018 Apr 30;2018:9480497. doi: 10.1155/2018/9480497. eCollection 2018.
Persistent antigen and germinal center B cells sustain T follicular helper cell responses and phenotype.
持续存在的抗原和生发中心 B 细胞维持 T 滤泡辅助细胞的反应和表型。
Immunity. 2013 Mar 21;38(3):596-605. doi: 10.1016/j.immuni.2012.11.020. Epub 2013 Mar 14.
4
Effects of adjuvants on IgG subclasses elicited by virus-like particles.佐剂对病毒样颗粒诱导的 IgG 亚类的影响。
J Transl Med. 2012 Jan 5;10:4. doi: 10.1186/1479-5876-10-4.
5
Sequence and structural convergence of broad and potent HIV antibodies that mimic CD4 binding.序列和结构上与 CD4 结合模拟广泛而有效的 HIV 抗体的趋同。
Science. 2011 Sep 16;333(6049):1633-7. doi: 10.1126/science.1207227. Epub 2011 Jul 14.
6
Enhanced mucosal immune responses to HIV virus-like particles containing a membrane-anchored adjuvant.增强含有膜锚定佐剂的 HIV 病毒样颗粒的黏膜免疫应答。
mBio. 2011 Feb 15;2(1):e00328-10. doi: 10.1128/mBio.00328-10. Print 2011.
7
TLR-based immune adjuvants.基于 Toll 样受体的免疫佐剂。
Vaccine. 2011 Apr 12;29(17):3341-55. doi: 10.1016/j.vaccine.2010.08.002. Epub 2010 Aug 14.
8
Structural basis for broad and potent neutralization of HIV-1 by antibody VRC01.抗体 VRC01 广谱且强效中和 HIV-1 的结构基础。
Science. 2010 Aug 13;329(5993):811-7. doi: 10.1126/science.1192819. Epub 2010 Jul 8.
9
Virus-like particle vaccine activates conventional B2 cells and promotes B cell differentiation to IgG2a producing plasma cells.病毒样颗粒疫苗可激活传统B2细胞，并促进B细胞分化为产生IgG2a的浆细胞。
Mol Immunol. 2009 Jun;46(10):1988-2001. doi: 10.1016/j.molimm.2009.03.008. Epub 2009 Apr 18.
10
Measuring HIV neutralization in a luciferase reporter gene assay.在荧光素酶报告基因检测中测量HIV中和作用。
Methods Mol Biol. 2009;485:395-405. doi: 10.1007/978-1-59745-170-3_26.