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。
What Is the Predictive Value of Animal Models for Vaccine Efficacy in Humans? Rigorous Simian Immunodeficiency Virus Vaccine Trials Can Be Instructive.
机构信息
Department of Pathology, University of Miami, Miami, Florida 33136.
出版信息
Cold Spring Harb Perspect Biol. 2018 Apr 2;10(4):a029504. doi: 10.1101/cshperspect.a029504.
Abstract
Simian immunodeficiency virus (SIV) challenge of rhesus macaques provides an invaluable tool to evaluate the clinical prospects of HIV-1 vaccine concepts. However, as with any animal model of human disease, it is crucial to understand the advantages and limitations of this system to maximize the translational value of SIV vaccine studies. Here, we discuss the importance of assessing the efficacy of vaccine prototypes using stringent SIV challenge regimens that mimic HIV-1 transmission and pathogenesis. We also review some of the cautionary tales of HIV-1 vaccine research because they provide general lessons for the preclinical assessment of vaccine candidates.
摘要
恒河猴感染猴免疫缺陷病毒（SIV）模型为评估 HIV-1 疫苗概念的临床前景提供了非常有价值的工具。然而，就像任何人类疾病的动物模型一样，了解该系统的优势和局限性对于最大限度地提高 SIV 疫苗研究的转化价值至关重要。在这里，我们讨论了使用模拟 HIV-1 传播和发病机制的严格 SIV 挑战方案来评估疫苗原型功效的重要性。我们还回顾了一些 HIV-1 疫苗研究的警示故事，因为它们为疫苗候选物的临床前评估提供了一般性的经验教训。
相似文献
1
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.
2
Monkeying around with HIV vaccines: using rhesus macaques to define 'gatekeepers' for clinical trials.摆弄HIV疫苗：利用恒河猴为临床试验确定“把关因素”
Nat Rev Immunol. 2009 Oct;9(10):717-28. doi: 10.1038/nri2636.
3
Early T Follicular Helper Cell Responses and Germinal Center Reactions Are Associated with Viremia Control in Immunized Rhesus Macaques.早期 T 滤泡辅助细胞反应和生发中心反应与免疫恒河猴的病毒血症控制相关。
J Virol. 2019 Feb 5;93(4). doi: 10.1128/JVI.01687-18. Print 2019 Feb 15.
4
Analysis of Complement-Mediated Lysis of Simian Immunodeficiency Virus (SIV) and SIV-Infected Cells Reveals Sex Differences in Vaccine-Induced Immune Responses in Rhesus Macaques.分析补体介导的猴免疫缺陷病毒（SIV）和感染 SIV 的细胞的溶解作用揭示了恒河猴疫苗诱导免疫反应中的性别差异。
J Virol. 2018 Sep 12;92(19). doi: 10.1128/JVI.00721-18. Print 2018 Oct 1.
5
Simian and feline immunodeficiency viruses: animal lentivirus models for evaluation of AIDS vaccines and antiviral agents.猿猴和猫科动物免疫缺陷病毒：用于评估艾滋病疫苗和抗病毒药物的动物慢病毒模型。
Antiviral Res. 1991 May;15(4):267-86. doi: 10.1016/0166-3542(91)90009-g.
6
Characterization and Implementation of a Diverse Simian Immunodeficiency Virus SIVsm Envelope Panel in the Assessment of Neutralizing Antibody Breadth Elicited in Rhesus Macaques by Multimodal Vaccines Expressing the SIVmac239 Envelope.在评估表达SIVmac239包膜的多模式疫苗在恒河猴中引发的中和抗体广度时，多样化的猿猴免疫缺陷病毒SIVsm包膜组合的表征与应用
J Virol. 2015 Aug;89(16):8130-51. doi: 10.1128/JVI.01221-14. Epub 2015 May 27.
7
Reduced Cell-Associated DNA and Improved Viral Control in Macaques following Passive Transfer of a Single Anti-V2 Monoclonal Antibody and Repeated Simian/Human Immunodeficiency Virus Challenges.在单次被动转移抗 V2 单克隆抗体和重复猴/人免疫缺陷病毒挑战后，猕猴体内细胞相关 DNA 减少和病毒控制得到改善。
J Virol. 2018 May 14;92(11). doi: 10.1128/JVI.02198-17. Print 2018 Jun 1.
8
Protection against mucosal simian immunodeficiency virus SIV(mac251) challenge by using replicating adenovirus-SIV multigene vaccine priming and subunit boosting.通过使用复制型腺病毒-SIV多基因疫苗初免和亚单位疫苗加强免疫来预防黏膜猿猴免疫缺陷病毒SIV（mac251）攻击。
J Virol. 2004 Mar;78(5):2212-21. doi: 10.1128/jvi.78.5.2212-2221.2004.
9
Targeted lymph-node immunization with whole inactivated simian immunodeficiency virus (SIV) or envelope and core subunit antigen vaccines does not reliably protect rhesus macaques from vaginal challenge with SIVmac251.用全灭活猴免疫缺陷病毒（SIV）或包膜及核心亚单位抗原疫苗进行靶向淋巴结免疫，不能可靠地保护恒河猴免受SIVmac251的阴道攻击。
AIDS. 1998 Jan 1;12(1):1-10. doi: 10.1097/00002030-199801000-00001.
10
Abrogation of attenuated lentivirus-induced protection in rhesus macaques by administration of depo-provera before intravaginal challenge with simian immunodeficiency virus mac239.在经阴道用猿猴免疫缺陷病毒mac239攻击之前给予醋酸甲羟孕酮，可消除减毒慢病毒诱导的恒河猴的保护作用。
J Infect Dis. 2004 Nov 1;190(9):1697-705. doi: 10.1086/424600. Epub 2004 Sep 24.
引用本文的文献
1
The heart of the matter: modeling HIV-associated cardiovascular comorbidities in nonhuman primate models.问题的核心：在非人类灵长类动物模型中模拟与HIV相关的心血管合并症
Front Cell Infect Microbiol. 2025 Apr 22;15:1556315. doi: 10.3389/fcimb.2025.1556315. eCollection 2025.
2
Tetravalent SARS-CoV-2 S1 Subunit Protein Vaccination Elicits Robust Humoral and Cellular Immune Responses in SIV-Infected Rhesus Macaque Controllers.四价严重急性呼吸综合征冠状病毒2（SARS-CoV-2）S1亚基蛋白疫苗接种在感染猴免疫缺陷病毒（SIV）的恒河猴病毒控制者中引发强大的体液和细胞免疫反应。
bioRxiv. 2023 Mar 16:2023.03.15.532808. doi: 10.1101/2023.03.15.532808.
3
Morphine suppresses peripheral responses and transforms brain myeloid gene expression to favor neuropathogenesis in SIV infection.吗啡抑制外周反应，并改变大脑髓样基因表达，有利于 SIV 感染中的神经发病机制。
Front Immunol. 2022 Nov 16;13:1012884. doi: 10.3389/fimmu.2022.1012884. eCollection 2022.
4
Antiretroviral therapy restores the homeostatic state of microglia in SIV-infected rhesus macaques.抗逆转录病毒疗法可恢复 SIV 感染恒河猴小胶质细胞的内稳态。
J Leukoc Biol. 2022 Nov;112(5):969-981. doi: 10.1002/JLB.3HI0422-635R. Epub 2022 Jun 10.
5
Nonhuman Primates in Translational Research.非人类灵长类动物在转化研究中的应用。
Annu Rev Anim Biosci. 2022 Feb 15;10:441-468. doi: 10.1146/annurev-animal-021419-083813.
6
Increased IL-6 expression precedes reliable viral detection in the rhesus macaque brain during acute SIV infection.在急性 SIV 感染期间，恒河猴大脑中 IL-6 表达增加先于可靠的病毒检测。
JCI Insight. 2021 Oct 22;6(20):e152013. doi: 10.1172/jci.insight.152013.
7
Interleukin-15 response signature predicts RhCMV/SIV vaccine efficacy.白细胞介素-15 反应特征可预测 RhCMV/SIV 疫苗的疗效。
PLoS Pathog. 2021 Jul 6;17(7):e1009278. doi: 10.1371/journal.ppat.1009278. eCollection 2021 Jul.
8
Recombinant Herpesvirus Vectors: Durable Immune Responses and Durable Protection against Simian Immunodeficiency Virus SIVmac239 Acquisition.重组单纯疱疹病毒载体：持久的免疫应答和对猴免疫缺陷病毒 SIVmac239 获得性感染的持久保护。
J Virol. 2021 Jun 24;95(14):e0033021. doi: 10.1128/JVI.00330-21.
9
Rectal Acquisition of Simian Immunodeficiency Virus (SIV) SIVmac239 Infection despite Vaccine-Induced Immune Responses against the Entire SIV Proteome.直肠获取猴免疫缺陷病毒（SIV），尽管针对整个 SIV 蛋白组产生了疫苗诱导的免疫反应，但仍会感染 SIVmac239。
J Virol. 2020 Nov 23;94(24). doi: 10.1128/JVI.00979-20.
10
Design of a Novel Multi Epitope-Based Vaccine for Pandemic Coronavirus Disease (COVID-19) by Vaccinomics and Probable Prevention Strategy against Avenging Zoonotics.基于疫苗学设计的新型多表位疫苗用于大流行性冠状病毒病 (COVID-19) 及对报复性人畜共患病的可能预防策略。
Eur J Pharm Sci. 2020 Aug 1;151:105387. doi: 10.1016/j.ejps.2020.105387. Epub 2020 May 23.
本文引用的文献
1
Rapid development of a DNA vaccine for Zika virus.寨卡病毒DNA疫苗的快速研发。
Science. 2016 Oct 14;354(6309):237-240. doi: 10.1126/science.aai9137. Epub 2016 Sep 22.
2
Protective efficacy of multiple vaccine platforms against Zika virus challenge in rhesus monkeys.多种疫苗平台对恒河猴寨卡病毒攻击的保护效力
Science. 2016 Sep 9;353(6304):1129-32. doi: 10.1126/science.aah6157. Epub 2016 Aug 4.
3
Vaccine protection against Zika virus from Brazil.来自巴西的针对寨卡病毒的疫苗防护
Nature. 2016 Aug 25;536(7617):474-8. doi: 10.1038/nature18952. Epub 2016 Jun 28.
4
A rhesus macaque model of Asian-lineage Zika virus infection.亚洲谱系寨卡病毒感染恒河猴模型。
Nat Commun. 2016 Jun 28;7:12204. doi: 10.1038/ncomms12204.
5
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.
6
Prospective Study of Acute HIV-1 Infection in Adults in East Africa and Thailand.东非和泰国成人急性HIV-1感染的前瞻性研究。
N Engl J Med. 2016 Jun 2;374(22):2120-30. doi: 10.1056/NEJMoa1508952. Epub 2016 May 18.
7
Broadly targeted CD8⁺ T cell responses restricted by major histocompatibility complex E.由主要组织相容性复合体E限制的广泛靶向性CD8⁺T细胞反应
Science. 2016 Feb 12;351(6274):714-20. doi: 10.1126/science.aac9475. Epub 2016 Jan 21.
8
Protective efficacy of adenovirus/protein vaccines against SIV challenges in rhesus monkeys.腺病毒/蛋白质疫苗对恒河猴感染猴免疫缺陷病毒的保护效力
Science. 2015 Jul 17;349(6245):320-4. doi: 10.1126/science.aab3886. Epub 2015 Jul 2.
9
Bottlenecks in HIV-1 transmission: insights from the study of founder viruses.人类免疫缺陷病毒1型传播中的瓶颈：来自奠基者病毒研究的见解
Nat Rev Microbiol. 2015 Jul;13(7):414-25. doi: 10.1038/nrmicro3471. Epub 2015 Jun 8.
10
The chimpanzee model for hepatitis B virus infection.乙型肝炎病毒感染的黑猩猩模型。
Cold Spring Harb Perspect Med. 2015 Jun 1;5(6):a021469. doi: 10.1101/cshperspect.a021469.
Zotero 插件