• 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

ICP8-vhs- HSV-2 疫苗表达 B7 共刺激分子优化了针对小鼠 HSV-2 感染的安全性和疗效。

ICP8-vhs- HSV-2 Vaccine Expressing B7 Costimulation Molecules Optimizes Safety and Efficacy against HSV-2 Infection in Mice.

机构信息

Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, 1100 South Grand Blvd., St. Louis, MO 63104, USA.

出版信息

Viruses. 2023 Jul 18;15(7):1570. doi: 10.3390/v15071570.

DOI:10.3390/v15071570
PMID:37515256
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10384616/
Abstract

Herpes simplex virus 2 (HSV-2) causes most sexually transmitted genital ulcerative disease. No effective prophylactic vaccine is currently available. Replication-defective (ICP8-) HSV stimulates immune responses in animals without producing progeny virus, making it potentially useful as a safe form of a live vaccine against HSV. We previously demonstrated that mice generate a stronger response to ICP8- virus encoding B7-2 costimulation molecules than to the parental replication-defective virus. We have also demonstrated enhanced immunogenicity of an ICP8-, virion host shutoff (vhs)- virus which can no longer destabilize viral and host mRNAs. Here, we constructed a triple mutant, ICP8-vhs-B7-2+ strain, and compared it to both double mutant viruses. Immunization of mice with a single dose of ICP8-B7-2+ or ICP8-vhs-B7-2+ virus decreased challenge virus replication in the vaginal mucosa, genital disease, and mortality more effectively than immunization with the ICP8-vhs- virus. Immunization with ICP8-B7-2+ or ICP8-vhs-B7-2+ virus also effectively suppressed subsequent HSV-2 infection of the nervous system compared to immunization with the ICP8-vhs- virus. ICP8-B7-2+ and ICP8-vhs-B7-2+ strains induced more IFN gamma-producing CD8 T cells and memory CD8 T cells than did ICP8-vhs- virus, potentially explaining the enhanced protective effects. Thus, B7 costimulation molecules expressed from a replication-defective vaccine can enhance vaccine efficacy, even in an immunocompetent host.

摘要

单纯疱疹病毒 2（HSV-2）引起大多数性传播的生殖器溃疡性疾病。目前尚无有效的预防性疫苗。复制缺陷（ICP8-）HSV 在不产生后代病毒的情况下刺激动物的免疫反应，使其有可能成为针对 HSV 的安全活疫苗形式。我们之前证明，与亲本复制缺陷病毒相比，携带 B7-2 共刺激分子的 ICP8-病毒在小鼠中产生更强的反应。我们还证明了不能再使病毒和宿主 mRNA 不稳定的 ICP8-、衣壳宿主关闭（vhs）-病毒的免疫原性增强。在这里，我们构建了一个三重突变体 ICP8-vhs-B7-2+株，并将其与两种双突变体病毒进行了比较。单次免疫 ICP8-B7-2+或 ICP8-vhs-B7-2+病毒可更有效地降低阴道黏膜、生殖器疾病和死亡率的挑战病毒复制，而免疫 ICP8-vhs-病毒效果较差。与免疫 ICP8-vhs-病毒相比，免疫 ICP8-B7-2+或 ICP8-vhs-B7-2+病毒还能更有效地抑制随后的 HSV-2 感染神经系统。与 ICP8-vhs-病毒相比，ICP8-B7-2+和 ICP8-vhs-B7-2+株诱导产生更多的 IFNγ 产生 CD8 T 细胞和记忆性 CD8 T 细胞，这可能解释了增强的保护作用。因此，表达自复制缺陷疫苗的 B7 共刺激分子可以增强疫苗的功效，即使在免疫功能正常的宿主中也是如此。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4169/10384616/62ac31ebe4ee/viruses-15-01570-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4169/10384616/e253db837453/viruses-15-01570-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4169/10384616/e8216c4c4c8b/viruses-15-01570-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4169/10384616/4d799568bb47/viruses-15-01570-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4169/10384616/9e7b7510c88e/viruses-15-01570-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4169/10384616/db37fb7369f4/viruses-15-01570-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4169/10384616/886be51abe05/viruses-15-01570-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4169/10384616/ac2405b8ad8a/viruses-15-01570-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4169/10384616/d95458033739/viruses-15-01570-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4169/10384616/62ac31ebe4ee/viruses-15-01570-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4169/10384616/e253db837453/viruses-15-01570-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4169/10384616/e8216c4c4c8b/viruses-15-01570-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4169/10384616/4d799568bb47/viruses-15-01570-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4169/10384616/9e7b7510c88e/viruses-15-01570-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4169/10384616/db37fb7369f4/viruses-15-01570-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4169/10384616/886be51abe05/viruses-15-01570-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4169/10384616/ac2405b8ad8a/viruses-15-01570-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4169/10384616/d95458033739/viruses-15-01570-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4169/10384616/62ac31ebe4ee/viruses-15-01570-g009.jpg

相似文献

1
ICP8-vhs- HSV-2 Vaccine Expressing B7 Costimulation Molecules Optimizes Safety and Efficacy against HSV-2 Infection in Mice.ICP8-vhs- HSV-2 疫苗表达 B7 共刺激分子优化了针对小鼠 HSV-2 感染的安全性和疗效。
Viruses. 2023 Jul 18;15(7):1570. doi: 10.3390/v15071570.
2
Virus-encoded b7-2 costimulation molecules enhance the protective capacity of a replication-defective herpes simplex virus type 2 vaccine in immunocompetent mice.病毒编码的共刺激分子b7-2增强了复制缺陷型单纯疱疹病毒2型疫苗在免疫活性小鼠中的保护能力。
J Virol. 2009 Jan;83(2):953-60. doi: 10.1128/JVI.02022-08. Epub 2008 Nov 5.
3
Disruption of virion host shutoff activity improves the immunogenicity and protective capacity of a replication-incompetent herpes simplex virus type 1 vaccine strain.病毒体宿主关闭活性的破坏提高了一种无复制能力的单纯疱疹病毒1型疫苗株的免疫原性和保护能力。
J Virol. 2000 Dec;74(23):11137-44. doi: 10.1128/jvi.74.23.11137-11144.2000.
4
B7 costimulation molecules expressed from the herpes simplex virus 2 genome rescue immune induction in B7-deficient mice.由单纯疱疹病毒2基因组表达的B7共刺激分子挽救了B7缺陷小鼠的免疫诱导。
J Virol. 2007 Nov;81(22):12200-9. doi: 10.1128/JVI.01224-07. Epub 2007 Sep 5.
5
B7 costimulation molecules encoded by replication-defective, vhs-deficient HSV-1 improve vaccine-induced protection against corneal disease.复制缺陷型、vhs 缺陷型单纯疱疹病毒 1 编码的 B7 共刺激分子可提高疫苗诱导的角膜疾病保护作用。
PLoS One. 2011;6(8):e22772. doi: 10.1371/journal.pone.0022772. Epub 2011 Aug 3.
6
Therapeutic immunization with a virion host shutoff-defective, replication-incompetent herpes simplex virus type 1 strain limits recurrent herpetic ocular infection.用病毒体宿主关闭缺陷、复制无能力的单纯疱疹病毒1型毒株进行治疗性免疫可限制复发性疱疹性眼部感染。
J Virol. 2002 Apr;76(8):3615-25. doi: 10.1128/jvi.76.8.3615-3625.2002.
7
Attenuated Herpes Simplex Virus 1 (HSV-1) Expressing a Mutant Form of ICP6 Stimulates a Strong Immune Response That Protects Mice against HSV-1-Induced Corneal Disease.单纯疱疹病毒 1（HSV-1）表达突变型 ICP6 的减毒病毒可刺激强烈的免疫反应，保护小鼠免受 HSV-1 诱导的角膜疾病。
J Virol. 2018 Aug 16;92(17). doi: 10.1128/JVI.01036-18. Print 2018 Sep 1.
8
Construction and properties of a herpes simplex virus 2 dl5-29 vaccine candidate strain encoding an HSV-1 virion host shutoff protein.构建并评价编码单纯疱疹病毒 1 型病毒粒子宿主关闭蛋白的单纯疱疹病毒 2 dl5-29 候选减毒活疫苗株。
Vaccine. 2010 Mar 24;28(15):2754-62. doi: 10.1016/j.vaccine.2010.01.030. Epub 2010 Jan 29.
9
Herpes simplex virus type 2 virion host shutoff protein regulates alpha/beta interferon but not adaptive immune responses during primary infection in vivo.2型单纯疱疹病毒病毒体宿主关闭蛋白在体内原发性感染期间调节α/β干扰素，但不调节适应性免疫反应。
J Virol. 2003 Sep;77(17):9337-45. doi: 10.1128/jvi.77.17.9337-9345.2003.
10
Construction and characterization of a replication-defective herpes simplex virus 2 ICP8 mutant strain and its use in immunization studies in a guinea pig model of genital disease.复制缺陷型单纯疱疹病毒2型ICP8突变株的构建、特性鉴定及其在豚鼠生殖器疾病模型免疫研究中的应用。
Virology. 1997 May 26;232(1):1-12. doi: 10.1006/viro.1997.8564.

本文引用的文献

1
Alphaherpesvirus Vaccines.甲型疱疹病毒疫苗
Curr Issues Mol Biol. 2021;41:469-508. doi: 10.21775/cimb.041.469. Epub 2020 Sep 23.
2
Herpes simplex virus: global infection prevalence and incidence estimates, 2016.单纯疱疹病毒：2016 年全球感染流行率和发病率估计。
Bull World Health Organ. 2020 May 1;98(5):315-329. doi: 10.2471/BLT.19.237149. Epub 2020 Mar 25.
3
A Randomized, Double-Blinded, Placebo-Controlled, Phase 1 Study of a Replication-Defective Herpes Simplex Virus (HSV) Type 2 Vaccine, HSV529, in Adults With or Without HSV Infection.
一项随机、双盲、安慰剂对照、1 期研究，评估复制缺陷型单纯疱疹病毒 2 型（HSV）疫苗 HSV529 在有或无 HSV 感染的成人中的效果。
J Infect Dis. 2019 Aug 9;220(6):990-1000. doi: 10.1093/infdis/jiz225.
4
The HSV-1 live attenuated VC2 vaccine provides protection against HSV-2 genital infection in the guinea pig model of genital herpes.HSV-1 活病毒减毒 VC2 疫苗在生殖器疱疹豚鼠模型中提供针对 HSV-2 生殖器感染的保护。
Vaccine. 2019 Jan 3;37(1):61-68. doi: 10.1016/j.vaccine.2018.11.042. Epub 2018 Nov 22.
5
Herpes simplex type 2 virus deleted in glycoprotein D protects against vaginal, skin and neural disease.糖蛋白D缺失的2型单纯疱疹病毒可预防阴道、皮肤和神经疾病。
Elife. 2015 Mar 10;4:e06054. doi: 10.7554/eLife.06054.
6
Global estimates of prevalent and incident herpes simplex virus type 2 infections in 2012.2012年全球单纯疱疹病毒2型感染的流行率和发病率估计数。
PLoS One. 2015 Jan 21;10(1):e114989. doi: 10.1371/journal.pone.0114989. eCollection 2015.
7
Seroprevalence of herpes simplex virus types 1 and 2--United States, 1999-2010.单纯疱疹病毒 1 型和 2 型的血清流行率 - 美国，1999-2010 年。
J Infect Dis. 2014 Feb 1;209(3):325-33. doi: 10.1093/infdis/jit458. Epub 2013 Oct 16.
8
Sexually transmitted infections among US women and men: prevalence and incidence estimates, 2008.美国男女人群中的性传播感染：2008 年的流行率和发病率估计。
Sex Transm Dis. 2013 Mar;40(3):187-93. doi: 10.1097/OLQ.0b013e318286bb53.
9
Efficacy results of a trial of a herpes simplex vaccine.一项单纯疱疹疫苗试验的疗效结果。
N Engl J Med. 2012 Jan 5;366(1):34-43. doi: 10.1056/NEJMoa1103151.
10
Cross-presentation and genome-wide screening reveal candidate T cells antigens for a herpes simplex virus type 1 vaccine.交叉呈递和全基因组筛选揭示候选 T 细胞抗原用于单纯疱疹病毒 1 型疫苗。
J Clin Invest. 2012 Feb;122(2):654-73. doi: 10.1172/JCI60556. Epub 2012 Jan 3.