通过被动免疫保护人源化小鼠免受反复阴道内HIV攻击：一种用于研究体内中和抗体功效的模型。
Protection of Humanized Mice From Repeated Intravaginal HIV Challenge by Passive Immunization: A Model for Studying the Efficacy of Neutralizing Antibodies In Vivo.
作者信息
Deruaz Maud, Moldt Brian, Le Khoa M, Power Karen A, Vrbanac Vladimir D, Tanno Serah, Ghebremichael Musie S, Allen Todd M, Tager Andrew M, Burton Dennis R, Luster Andrew D
机构信息
Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston.
Department of Immunology and Microbial Science, Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, and IAVI Neutralizing Antibody Center, Scripps Research Institute, La Jolla, California.
出版信息
J Infect Dis. 2016 Aug 15;214(4):612-6. doi: 10.1093/infdis/jiw203. Epub 2016 Jun 29.
Abstract
Humanized mice reconstituted with a human immune system can be mucosally infected with human immunodeficiency virus (HIV), opening up the possibility of studying HIV transmission in a small-animal model. Here we report that passive immunization with the broadly neutralizing antibody b12 protected humanized mice against repetitive intravaginal infection in a dose-dependent manner. In addition, treatment with the antibody PGT126, which is more potent in vitro, was more efficacious in vivo and provided sterilizing protection. Our results demonstrate that humanized mice can be used as a small-animal model to study the efficacy and mechanism of broadly neutralizing antibody protection against HIV acquisition.
摘要
用人免疫系统重建的人源化小鼠可通过黏膜感染人类免疫缺陷病毒（HIV），这为在小动物模型中研究HIV传播开辟了可能性。在此我们报告，用广泛中和抗体b12进行被动免疫以剂量依赖方式保护人源化小鼠免受重复性阴道内感染。此外，在体外更有效的抗体PGT126治疗在体内更有效，并提供了无菌保护。我们的结果表明，人源化小鼠可作为小动物模型来研究广泛中和抗体预防HIV感染的疗效和机制。
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本文引用的文献
1
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Nature. 2015 Jun 25;522(7557):487-91. doi: 10.1038/nature14411. Epub 2015 Apr 8.
2
Broadly neutralizing anti-HIV-1 antibodies require Fc effector functions for in vivo activity.广谱中和抗 HIV-1 抗体需要 Fc 效应功能才能在体内发挥作用。
Cell. 2014 Sep 11;158(6):1243-1253. doi: 10.1016/j.cell.2014.08.023.
3
Vectored immunoprophylaxis protects humanized mice from mucosal HIV transmission.载体免疫预防可保护人源化小鼠免受黏膜 HIV 传播。
Nat Med. 2014 Mar;20(3):296-300. doi: 10.1038/nm.3471. Epub 2014 Feb 9.
4
Antibodies in HIV-1 vaccine development and therapy.HIV-1 疫苗开发和治疗中的抗体。
Science. 2013 Sep 13;341(6151):1199-204. doi: 10.1126/science.1241144.
5
Antibody and antiretroviral preexposure prophylaxis prevent cervicovaginal HIV-1 infection in a transgenic mouse model.抗体和抗逆转录病毒药物预先暴露预防在转基因小鼠模型中预防宫颈阴道 HIV-1 感染。
J Virol. 2013 Aug;87(15):8535-44. doi: 10.1128/JVI.00868-13. Epub 2013 May 29.
6
HIV therapy by a combination of broadly neutralizing antibodies in humanized mice.在人源化小鼠中通过广泛中和抗体的组合进行 HIV 治疗。
Nature. 2012 Dec 6;492(7427):118-22. doi: 10.1038/nature11604. Epub 2012 Oct 24.
7
Highly potent HIV-specific antibody neutralization in vitro translates into effective protection against mucosal SHIV challenge in vivo.在体外具有高效的 HIV 特异性抗体中和作用可转化为体内对黏膜 SHIV 挑战的有效保护。
Proc Natl Acad Sci U S A. 2012 Nov 13;109(46):18921-5. doi: 10.1073/pnas.1214785109. Epub 2012 Oct 25.
8
Inhibitory effect of HIV-specific neutralizing IgA on mucosal transmission of HIV in humanized mice.HIV 特异性中和 IgA 抑制人源化小鼠肠道内 HIV 的传播。
Blood. 2012 Nov 29;120(23):4571-82. doi: 10.1182/blood-2012-04-422303. Epub 2012 Oct 11.
9
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Virology. 2012 Oct 25;432(2):505-10. doi: 10.1016/j.virol.2012.06.025. Epub 2012 Jul 24.
10
Broad neutralization coverage of HIV by multiple highly potent antibodies.多种高效价抗体对 HIV 的广泛中和覆盖。
Nature. 2011 Sep 22;477(7365):466-70. doi: 10.1038/nature10373.
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