动物模型对人类疫苗疗效的预测价值是什么？桥接研究和与物种无关的保护相关性的重要性。
What Is the Predictive Value of Animal Models for Vaccine Efficacy in Humans? The Importance of Bridging Studies and Species-Independent Correlates of Protection.
机构信息
Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland 20993.
出版信息
Cold Spring Harb Perspect Biol. 2018 Apr 2;10(4):a028902. doi: 10.1101/cshperspect.a028902.
Abstract
Animal models have played a pivotal role in all stages of vaccine development. Their predictive value for vaccine effectiveness depends on the pathogen, the robustness of the animal challenge model, and the correlates of protection (if known). This article will cover key questions regarding bridging animal studies to efficacy trials in humans. Examples include human papillomavirus (HPV) vaccine in which animal protection after vaccination with heterologous prototype virus-like particles (VLPs) predicted successful efficacy trials in humans, and a recent approval of anthrax vaccine in accordance with the "Animal Rule." The establishment of animal models predictive of vaccine effectiveness in humans has been fraught with difficulties with low success rate to date. Challenges facing the use of animal models for vaccine development against Ebola and HIV will be discussed.
摘要
动物模型在疫苗开发的各个阶段都发挥了关键作用。它们对疫苗有效性的预测价值取决于病原体、动物挑战模型的稳健性以及保护相关性（如果已知）。本文将涵盖将动物研究与人体功效试验联系起来的关键问题。例如，人乳头瘤病毒（HPV）疫苗，其中接种异源原型病毒样颗粒（VLPs）后的动物保护预测了人体功效试验的成功，以及最近根据“动物规则”批准了炭疽疫苗。建立能够预测人类疫苗有效性的动物模型一直充满困难，迄今为止成功率较低。本文将讨论在开发针对埃博拉病毒和艾滋病毒的疫苗时使用动物模型所面临的挑战。
相似文献
1
What Is the Predictive Value of Animal Models for Vaccine Efficacy in Humans? The Importance of Bridging Studies and Species-Independent Correlates of Protection.动物模型对人类疫苗疗效的预测价值是什么？桥接研究和与物种无关的保护相关性的重要性。
Cold Spring Harb Perspect Biol. 2018 Apr 2;10(4):a028902. doi: 10.1101/cshperspect.a028902.
2
What Is the Predictive Value of Animal Models for Vaccine Efficacy in Humans? Rigorous Simian Immunodeficiency Virus Vaccine Trials Can Be Instructive.动物模型对人类疫苗疗效的预测价值如何？严格的猴免疫缺陷病毒疫苗试验可以提供有启发性的信息。
Cold Spring Harb Perspect Biol. 2018 Apr 2;10(4):a029504. doi: 10.1101/cshperspect.a029504.
3
What Is the Predictive Value of Animal Models for Vaccine Efficacy in Humans? Consideration of Strategies to Improve the Value of Animal Models.动物模型对人类疫苗疗效的预测价值如何？考虑提高动物模型价值的策略。
Cold Spring Harb Perspect Biol. 2018 Apr 2;10(4):a031583. doi: 10.1101/cshperspect.a031583.
4
Broad Cross-Protection Is Induced in Preclinical Models by a Human Papillomavirus Vaccine Composed of L1/L2 Chimeric Virus-Like Particles.由L1/L2嵌合病毒样颗粒组成的人乳头瘤病毒疫苗在临床前模型中诱导产生广泛的交叉保护作用。
J Virol. 2016 Jun 24;90(14):6314-25. doi: 10.1128/JVI.00449-16. Print 2016 Jul 15.
5
An update of prophylactic human papillomavirus L1 virus-like particle vaccine clinical trial results.预防性人乳头瘤病毒L1病毒样颗粒疫苗临床试验结果的更新
Vaccine. 2008 Aug 19;26 Suppl 10(Suppl 10):K53-61. doi: 10.1016/j.vaccine.2008.06.002.
6
Bridging non-human primate correlates of protection to reassess the Anthrax Vaccine Adsorbed booster schedule in humans.建立非人类灵长类动物的保护相关性以重新评估人类吸附炭疽疫苗的加强免疫程序。
Vaccine. 2015 Jul 17;33(31):3709-16. doi: 10.1016/j.vaccine.2015.05.091. Epub 2015 Jun 10.
7
Human papillomavirus first and second generation vaccines-current status and future directions.人乳头瘤病毒第一代和第二代疫苗——现状与未来方向
Biol Chem. 2017 Jul 26;398(8):871-889. doi: 10.1515/hsz-2017-0105.
8
Chapter 16: Prophylactic human papillomavirus vaccines.第16章：预防性人乳头瘤病毒疫苗
J Natl Cancer Inst Monogr. 2003(31):111-6. doi: 10.1093/oxfordjournals.jncimonographs.a003472.
9
Toward a human papillomavirus vaccine.迈向人乳头瘤病毒疫苗。
Dermatol Clin. 1998 Oct;16(4):835-8. doi: 10.1016/s0733-8635(05)70056-5.
10
Human papillomavirus vaccines.人乳头瘤病毒疫苗
Semin Cancer Biol. 1999 Dec;9(6):431-44. doi: 10.1006/scbi.1999.0147.
引用本文的文献
1
Innovative micro physiological systems for vaccine development.用于疫苗开发的创新型微生理系统。
Hum Vaccin Immunother. 2025 Dec;21(1):2518641. doi: 10.1080/21645515.2025.2518641. Epub 2025 Jun 17.
2
Screening for variable drug responses using human iPSC cohorts.使用人类诱导多能干细胞队列筛选药物反应的变异性。
PLoS One. 2025 May 30;20(5):e0323953. doi: 10.1371/journal.pone.0323953. eCollection 2025.
3
A next-generation system for smoke inhalation integrated with a breathing lung-on-chip to model human lung responses to cigarette exposure.一种与呼吸肺芯片集成的下一代烟雾吸入系统，用于模拟人类肺部对香烟暴露的反应。
Sci Rep. 2025 May 25;15(1):18181. doi: 10.1038/s41598-025-00438-z.
4
A new dawn: Vitalising translational oncology research in Africa with the help of advanced cell culture models.新的曙光：借助先进的细胞培养模型振兴非洲转化肿瘤学研究。
Transl Oncol. 2025 Jun;56:102391. doi: 10.1016/j.tranon.2025.102391. Epub 2025 Apr 13.
5
Advanced liver-on-chip model mimicking hepatic lobule with continuous microvascular network via high-definition laser patterning.通过高清激光图案化模拟具有连续微血管网络的肝小叶的先进芯片肝脏模型。
Mater Today Bio. 2025 Mar 7;32:101643. doi: 10.1016/j.mtbio.2025.101643. eCollection 2025 Jun.
6
Deep Thought on the HIV Cured Cases: Where Have We Been and What Lies Ahead?对艾滋病治愈病例的深度思考：我们走过了哪些历程，未来又将如何？
Biomolecules. 2025 Mar 5;15(3):378. doi: 10.3390/biom15030378.
7
Assessment of Models of the Human Buccal Mucosa for Vaccine and Adjuvant Development.用于疫苗和佐剂开发的人体颊黏膜模型评估
Mol Pharm. 2025 Jun 2;22(6):2868-2880. doi: 10.1021/acs.molpharmaceut.4c01186. Epub 2025 Mar 26.
8
Autonomous Nucleic Acid and Protein Nanocomputing Agents Engineered to Operate in Living Cells.经设计可在活细胞中运行的自主核酸和蛋白质纳米计算剂。
ACS Nano. 2025 Jan 21;19(2):1865-1883. doi: 10.1021/acsnano.4c13663. Epub 2025 Jan 6.
9
Tonsil explants as a human model to study vaccine responses.扁桃体外植体作为研究疫苗反应的人体模型。
Front Immunol. 2024 Sep 17;15:1425455. doi: 10.3389/fimmu.2024.1425455. eCollection 2024.
10
A noninvasive BCG skin challenge model for assessing tuberculosis vaccine efficacy.一种用于评估结核疫苗效力的非侵入性卡介苗皮肤挑战模型。
PLoS Biol. 2024 Aug 19;22(8):e3002766. doi: 10.1371/journal.pbio.3002766. eCollection 2024 Aug.
本文引用的文献
1
A Randomized, Controlled Trial of ZMapp for Ebola Virus Infection.ZMapp治疗埃博拉病毒感染的随机对照试验。
N Engl J Med. 2016 Oct 13;375(15):1448-1456. doi: 10.1056/NEJMoa1604330.
2
Antibody-Mediated Internalization of Infectious HIV-1 Virions Differs among Antibody Isotypes and Subclasses.抗体介导的感染性HIV-1病毒粒子的内化在抗体同种型和亚类之间存在差异。
PLoS Pathog. 2016 Aug 31;12(8):e1005817. doi: 10.1371/journal.ppat.1005817. eCollection 2016 Aug.
3
Nonhuman primate models for the evaluation of HIV-1 preventive vaccine strategies: model parameter considerations and consequences.用于评估HIV-1预防性疫苗策略的非人灵长类动物模型：模型参数考量及影响
Curr Opin HIV AIDS. 2016 Nov;11(6):546-554. doi: 10.1097/COH.0000000000000311.
4
IgG Binding Characteristics of Rhesus Macaque FcγR.恒河猴FcγR的IgG结合特性
J Immunol. 2016 Oct 1;197(7):2936-47. doi: 10.4049/jimmunol.1502252. Epub 2016 Aug 24.
5
Derivation and Characterization of Pathogenic Transmitted/Founder Molecular Clones from Simian Immunodeficiency Virus SIVsmE660 and SIVmac251 following Mucosal Infection.黏膜感染后从猿猴免疫缺陷病毒SIVsmE660和SIVmac251衍生并鉴定致病性传播/奠基分子克隆
J Virol. 2016 Sep 12;90(19):8435-53. doi: 10.1128/JVI.00718-16. Print 2016 Oct 1.
6
Envelope residue 375 substitutions in simian-human immunodeficiency viruses enhance CD4 binding and replication in rhesus macaques.猿猴-人类免疫缺陷病毒中包膜残基375的替换增强了恒河猴体内的CD4结合及病毒复制。
Proc Natl Acad Sci U S A. 2016 Jun 14;113(24):E3413-22. doi: 10.1073/pnas.1606636113. Epub 2016 May 31.
7
Adjuvant-dependent innate and adaptive immune signatures of risk of SIVmac251 acquisition.依赖佐剂的SIVmac251感染风险的固有免疫和适应性免疫特征。
Nat Med. 2016 Jul;22(7):762-70. doi: 10.1038/nm.4105. Epub 2016 May 30.
8
Evaluation of Convalescent Plasma for Ebola Virus Disease in Guinea.几内亚埃博拉病毒病恢复期血浆的评估
N Engl J Med. 2016 Jan 7;374(1):33-42. doi: 10.1056/NEJMoa1511812.
9
Use of ChAd3-EBO-Z Ebola virus vaccine in Malian and US adults, and boosting of Malian adults with MVA-BN-Filo: a phase 1, single-blind, randomised trial, a phase 1b, open-label and double-blind, dose-escalation trial, and a nested, randomised, double-blind, placebo-controlled trial.ChAd3-EBO-Z埃博拉病毒疫苗在马里和美国成年人中的应用，以及用MVA-BN-Filo对马里成年人进行加强免疫：一项1期单盲随机试验、一项1b期开放标签和双盲剂量递增试验，以及一项嵌套随机双盲安慰剂对照试验。
Lancet Infect Dis. 2016 Jan;16(1):31-42. doi: 10.1016/S1473-3099(15)00362-X. Epub 2015 Nov 4.
10
Dissecting Polyclonal Vaccine-Induced Humoral Immunity against HIV Using Systems Serology.利用系统血清学剖析多克隆疫苗诱导的抗HIV体液免疫。
Cell. 2015 Nov 5;163(4):988-98. doi: 10.1016/j.cell.2015.10.027.
Zotero 插件