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1
Chimpanzees immunized with recombinant soluble CD4 develop anti-self CD4 antibody responses with anti-human immunodeficiency virus activity.用重组可溶性CD4免疫的黑猩猩会产生具有抗人类免疫缺陷病毒活性的抗自身CD4抗体反应。
Proc Natl Acad Sci U S A. 1992 Jun 1;89(11):5103-7. doi: 10.1073/pnas.89.11.5103.
2
Immunization of simian immunodeficiency virus-infected rhesus monkeys with soluble human CD4 elicits an antiviral response.用可溶性人CD4免疫感染猿猴免疫缺陷病毒的恒河猴可引发抗病毒反应。
Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):4616-20. doi: 10.1073/pnas.88.11.4616.
3
Soluble human CD4 elicits an antibody response in rhesus monkeys that inhibits simian immunodeficiency virus replication.
Proc Natl Acad Sci U S A. 1991 Jan 1;88(1):120-4. doi: 10.1073/pnas.88.1.120.
4
A humanized form of a CD4-specific monoclonal antibody exhibits decreased antigenicity and prolonged plasma half-life in rhesus monkeys while retaining its unique biological and antiviral properties.一种人源化形式的CD4特异性单克隆抗体在恒河猴中表现出抗原性降低和血浆半衰期延长，同时保留其独特的生物学和抗病毒特性。
AIDS Res Hum Retroviruses. 1997 Jul 20;13(11):933-43. doi: 10.1089/aid.1997.13.933.
5
Antibody responses elicited in macaques immunized with human immunodeficiency virus type 1 (HIV-1) SF162-derived gp140 envelope immunogens: comparison with those elicited during homologous simian/human immunodeficiency virus SHIVSF162P4 and heterologous HIV-1 infection.用1型人类免疫缺陷病毒（HIV-1）SF162衍生的gp140包膜免疫原免疫的猕猴引发的抗体反应：与同源猿猴/人类免疫缺陷病毒SHIVSF162P4和异源HIV-1感染期间引发的抗体反应的比较。
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6
A glycan shield on chimpanzee CD4 protects against infection by primate lentiviruses (HIV/SIV).黑猩猩 CD4 上的糖蛋白盾牌可防止灵长类慢病毒（HIV/SIV）感染。
Proc Natl Acad Sci U S A. 2019 Jun 4;116(23):11460-11469. doi: 10.1073/pnas.1813909116. Epub 2019 May 21.
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Vaccination with the Conserved Caveolin-1 Binding Motif in Human Immunodeficiency Virus Type 1 Glycoprotein gp41 Delays the Onset of Viral Infection and Provides Partial Protection in Simian/Human Immunodeficiency Virus-Challenged Cynomolgus Macaques.用人类免疫缺陷病毒 1 糖蛋白 gp41 中的保守 caveolin-1 结合基序进行免疫接种可延迟病毒感染的发作，并为感染猴免疫缺陷病毒的食蟹猴提供部分保护。
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Vaccination of rhesus macaques with recombinant Mycobacterium bovis bacillus Calmette-Guérin Env V3 elicits neutralizing antibody-mediated protection against simian-human immunodeficiency virus with a homologous but not a heterologous V3 motif.用重组卡介苗（Mycobacterium bovis bacillus Calmette-Guérin）Env V3免疫恒河猴，可引发中和抗体介导的针对猿猴-人类免疫缺陷病毒的保护作用，该保护作用针对具有同源而非异源V3基序的病毒。
J Virol. 2005 Feb;79(3):1452-62. doi: 10.1128/JVI.79.3.1452-1462.2005.
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Cross-Linking of a CD4-Mimetic Miniprotein with HIV-1 Env gp140 Alters Kinetics and Specificities of Antibody Responses against HIV-1 Env in Macaques.一种模拟CD4的微小蛋白质与HIV-1包膜糖蛋白gp140的交联改变了猕猴体内针对HIV-1包膜的抗体反应动力学和特异性。
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Increased, Durable B-Cell and ADCC Responses Associated with T-Helper Cell Responses to HIV-1 Envelope in Macaques Vaccinated with gp140 Occluded at the CD4 Receptor Binding Site.在接种CD4受体结合位点被封闭的gp140的猕猴中，与针对HIV-1包膜的辅助性T细胞反应相关的增强、持久的B细胞和ADCC反应。
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引用本文的文献

1
An HIV gp120-CD4 Immunogen Does Not Elicit Autoimmune Antibody Responses in Cynomolgus Macaques.一种HIV gp120-CD4免疫原不会在食蟹猴中引发自身免疫抗体反应。
Clin Vaccine Immunol. 2016 Jul 5;23(7):618-27. doi: 10.1128/CVI.00115-16. Print 2016 Jul.
2
Generation of MHC class I-restricted cytotoxic T cell lines and clones against colonic epithelial cells from ulcerative colitis.针对溃疡性结肠炎患者结肠上皮细胞产生MHC I类限制性细胞毒性T细胞系及克隆。
J Clin Immunol. 1999 Jan;19(1):77-85. doi: 10.1023/a:1020570719888.
3
Pathogenesis of human immunodeficiency virus infection.人类免疫缺陷病毒感染的发病机制
Microbiol Rev. 1993 Mar;57(1):183-289. doi: 10.1128/mr.57.1.183-289.1993.
4
Active immunity against the CD4 receptor by using an antibody antigenized with residues 41-55 of the first extracellular domain.通过使用用第一细胞外结构域的41-55位残基进行抗原化的抗体来获得针对CD4受体的主动免疫。
Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):11683-7. doi: 10.1073/pnas.90.24.11683.
5
Synergistic inhibition of human immunodeficiency virus type 1 envelope glycoprotein-mediated cell fusion and infection by an antibody to CD4 domain 2 in combination with anti-gp120 antibodies.抗CD4结构域2抗体与抗gp120抗体联合对人免疫缺陷病毒1型包膜糖蛋白介导的细胞融合和感染的协同抑制作用
J Virol. 1995 Jul;69(7):4267-73. doi: 10.1128/JVI.69.7.4267-4273.1995.
6
A human recombinant Fab identifies a human immunodeficiency virus type 1-induced conformational change in cell surface-expressed CD4.一种人重组Fab可识别1型人类免疫缺陷病毒诱导的细胞表面表达的CD4的构象变化。
J Virol. 1995 Sep;69(9):5734-42. doi: 10.1128/JVI.69.9.5734-5742.1995.
7
CD4 and its role in infection of rabbit cell lines by human immunodeficiency virus type 1.CD4及其在1型人类免疫缺陷病毒感染兔细胞系中的作用。
Proc Natl Acad Sci U S A. 1992 Sep 1;89(17):7963-7. doi: 10.1073/pnas.89.17.7963.

本文引用的文献

1
HIV infection is blocked in vitro by recombinant soluble CD4.在体外，重组可溶性CD4可阻断HIV感染。
Nature. 1988 Jan 7;331(6151):76-8. doi: 10.1038/331076a0.
2
Effect of recombinant soluble CD4 in rhesus monkeys infected with simian immunodeficiency virus of macaques.重组可溶性CD4对感染猕猴猿猴免疫缺陷病毒的恒河猴的影响。
Nature. 1989 Jan 19;337(6204):267-70. doi: 10.1038/337267a0.
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Monoclonal antibodies reactive with the T cell receptor zeta chain: production and characterization using a new method.
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The safety and pharmacokinetics of recombinant soluble CD4 (rCD4) in subjects with the acquired immunodeficiency syndrome (AIDS) and AIDS-related complex. A phase 1 study.重组可溶性CD4（rCD4）在获得性免疫缺陷综合征（AIDS）和AIDS相关综合征患者中的安全性和药代动力学。一项1期研究。
Ann Intern Med. 1990 Feb 15;112(4):254-61. doi: 10.7326/0003-4819-112-4-.
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Recombinant soluble CD4 therapy in patients with the acquired immunodeficiency syndrome (AIDS) and AIDS-related complex. A phase I-II escalating dosage trial.
Ann Intern Med. 1990 Feb 15;112(4):247-53. doi: 10.7326/0003-4819-112-4-247.
6
Antibody raised against soluble CD4-rgp120 complex recognizes the CD4 moiety and blocks membrane fusion without inhibiting CD4-gp120 binding.针对可溶性CD4-rgp120复合物产生的抗体可识别CD4部分，并阻断膜融合，而不抑制CD4与gp120的结合。
J Exp Med. 1990 Oct 1;172(4):1143-50. doi: 10.1084/jem.172.4.1143.
7
A CD4 domain important for HIV-mediated syncytium formation lies outside the virus binding site.对HIV介导的合胞体形成至关重要的CD4结构域位于病毒结合位点之外。
Cell. 1990 Mar 9;60(5):747-54. doi: 10.1016/0092-8674(90)90089-w.
8
Immunization of simian immunodeficiency virus-infected rhesus monkeys with soluble human CD4 elicits an antiviral response.用可溶性人CD4免疫感染猿猴免疫缺陷病毒的恒河猴可引发抗病毒反应。
Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):4616-20. doi: 10.1073/pnas.88.11.4616.
9
Soluble human CD4 elicits an antibody response in rhesus monkeys that inhibits simian immunodeficiency virus replication.
Proc Natl Acad Sci U S A. 1991 Jan 1;88(1):120-4. doi: 10.1073/pnas.88.1.120.
10
Immunization with soluble murine CD4 induces an anti-self antibody response without causing impairment of immune function.用可溶性小鼠CD4进行免疫接种可诱导自身抗体反应，而不会导致免疫功能受损。
J Immunol. 1991 Sep 1;147(5):1470-6.

用重组可溶性CD4免疫的黑猩猩会产生具有抗人类免疫缺陷病毒活性的抗自身CD4抗体反应。

Chimpanzees immunized with recombinant soluble CD4 develop anti-self CD4 antibody responses with anti-human immunodeficiency virus activity.

作者信息

Watanabe M, Boyson J E, Lord C I, Letvin N L

机构信息

Harvard Medical School, New England Regional Primate Research Center, Southborough, MA 01772.

出版信息

Proc Natl Acad Sci U S A. 1992 Jun 1;89(11):5103-7. doi: 10.1073/pnas.89.11.5103.

DOI:10.1073/pnas.89.11.5103
PMID:1594618
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC49237/
Abstract

In view of the efficiency with which human immunodeficiency virus replication can be blocked in vitro with anti-CD4 antibodies, the elicitation of an anti-CD4 antibody response through active immunization might represent a useful therapeutic strategy for AIDS. Here we demonstrate that immunization of chimpanzees with recombinant soluble human CD4 elicited an anti-CD4 antibody response. The elicited antibody bound self CD4 on digitonin-treated but not freshly isolated lymphocytes. Nevertheless, this antibody blocked human immunodeficiency virus replication in chimpanzee and human lymphocytes. These observations suggest that immunization with recombinant soluble CD4 from human immunodeficiency virus-infected humans may be feasible and therapeutically beneficial.

摘要

鉴于抗CD4抗体在体外能够有效阻断人类免疫缺陷病毒的复制，通过主动免疫引发抗CD4抗体反应可能是一种治疗艾滋病的有效策略。在此，我们证明用重组可溶性人CD4免疫黑猩猩可引发抗CD4抗体反应。所引发的抗体可与经洋地黄皂苷处理的淋巴细胞上的自身CD4结合，但不能与新鲜分离的淋巴细胞上的自身CD4结合。然而，这种抗体可阻断黑猩猩和人类淋巴细胞中的人类免疫缺陷病毒复制。这些观察结果表明，用来自感染人类免疫缺陷病毒的人的重组可溶性CD4进行免疫可能是可行的，并且在治疗上有益。