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恒河猴感染 SHIV 后阴道内潜伏时间，以及 VRC01 和抗 α4β7 治疗的影响。

Delayed vaginal SHIV infection in VRC01 and anti-α4β7 treated rhesus macaques.

机构信息

Center for Biomedical Research, Population Council, New York, New York, United States of America.

Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, United States of America.

出版信息

PLoS Pathog. 2019 May 13;15(5):e1007776. doi: 10.1371/journal.ppat.1007776. eCollection 2019 May.

DOI:10.1371/journal.ppat.1007776
PMID:31083697
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6533011/
Abstract

VRC01 protects macaques from vaginal SHIV infection after a single high-dose challenge. Infusion of a simianized anti-α4β7 mAb (Rh-α4β7) just prior to, and during repeated vaginal exposures to SIVmac251 partially protected macaques from vaginal SIV infection and rescued CD4+ T cells. To investigate the impact of combining VRC01 and Rh-α4β7 on SHIV infection, 3 groups of macaques were treated with a suboptimal dosing of VRC01 alone or in combination with Rh-α4β7 or with control antibodies prior to the initiation of weekly vaginal exposures to a high dose (1000 TCID50) of SHIVAD8-EO. The combination Rh-α4β7-VRC01 significantly delayed SHIVAD8-EO vaginal infection. Following infection, VRC01-Rh-α4β7-treated macaques maintained higher CD4+ T cell counts and exhibited lower rectal SIV-DNA loads compared to controls. Interestingly, VRC01-Rh-α4β7-treated macaques had fewer IL-17-producing cells in the blood and the gut during the acute phase of infection. Moreover, higher T cell responses to the V2-loop of the SHIVAD8-EO envelope in the VRC01-Rh-α4β7 group inversely correlated with set point viremia. The combination of suboptimal amounts of VRC01 and Rh-α4β7 delayed infection, altered antiviral immune responses and minimized CD4+ T cell loss. Further exploration of the effect of combining bNAbs with Rh-α4β7 on SIV/HIV infection and antiviral immune responses is warranted and may lead to novel preventive and therapeutic strategies.

摘要

VRC01 在单次高剂量挑战后可保护猕猴免受阴道 SHIV 感染。在反复阴道暴露于 SIVmac251 之前和期间输注模拟化抗 α4β7 mAb（Rh-α4β7）可部分保护猕猴免受阴道 SIV 感染并挽救 CD4+T 细胞。为了研究 VRC01 和 Rh-α4β7 联合使用对 SHIV 感染的影响，3 组猕猴在用亚最佳剂量的 VRC01 单独或与 Rh-α4β7 联合或与对照抗体治疗后开始每周阴道暴露于高剂量（1000 TCID50）SHIVAD8-EO。组合 Rh-α4β7-VRC01 显著延迟了 SHIVAD8-EO 阴道感染。感染后，与对照组相比，VRC01-Rh-α4β7 治疗的猕猴保持更高的 CD4+T 细胞计数，并表现出更低的直肠 SIV-DNA 负荷。有趣的是，VRC01-Rh-α4β7 治疗的猕猴在感染的急性期血液和肠道中产生 IL-17 的细胞较少。此外，VRC01-Rh-α4β7 组对 SHIVAD8-EO 包膜 V2 环的 T 细胞反应与病毒学临界点呈负相关。亚最佳剂量的 VRC01 和 Rh-α4β7 的组合延迟了感染，改变了抗病毒免疫反应，并最大限度地减少了 CD4+T 细胞的损失。进一步探索联合使用 bNAbs 和 Rh-α4β7 对 SIV/HIV 感染和抗病毒免疫反应的影响是必要的，可能会导致新的预防和治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e67d/6533011/e28dfb12f822/ppat.1007776.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e67d/6533011/07a425d0c2ca/ppat.1007776.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e67d/6533011/5243b7ed0598/ppat.1007776.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e67d/6533011/95d7516ed172/ppat.1007776.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e67d/6533011/97cc3a09f665/ppat.1007776.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e67d/6533011/e28dfb12f822/ppat.1007776.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e67d/6533011/07a425d0c2ca/ppat.1007776.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e67d/6533011/5243b7ed0598/ppat.1007776.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e67d/6533011/95d7516ed172/ppat.1007776.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e67d/6533011/97cc3a09f665/ppat.1007776.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e67d/6533011/e28dfb12f822/ppat.1007776.g005.jpg

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本文引用的文献

1
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Science. 2019 Sep 6;365(6457):1025-1029. doi: 10.1126/science.aav6695.
2
Anti-α4β7 therapy targets lymphoid aggregates in the gastrointestinal tract of HIV-1-infected individuals.抗 α4β7 治疗针对 HIV-1 感染个体胃肠道中的淋巴聚集物。
Sci Transl Med. 2018 Oct 3;10(461). doi: 10.1126/scitranslmed.aau4711.
3
Select gp120 V2 domain specific antibodies derived from HIV and SIV infection and vaccination inhibit gp120 binding to α4β7.
抗 αβ 单克隆抗体偶联纳米颗粒阻断恒河猴阴道内 T 细胞上的整合素 αβ。
Sci Adv. 2020 Aug 21;6(34). doi: 10.1126/sciadv.abb9853. Print 2020 Aug.
4
Broadly neutralizing plasma antibodies effective against autologous circulating viruses in infants with multivariant HIV-1 infection.广谱中和血浆抗体对多变异 HIV-1 感染婴儿体内自身循环病毒有效。
Nat Commun. 2020 Sep 2;11(1):4409. doi: 10.1038/s41467-020-18225-x.
5
SMAC Mimetic Plus Triple-Combination Bispecific HIVxCD3 Retargeting Molecules in SHIV.C.CH505-Infected, Antiretroviral Therapy-Suppressed Rhesus Macaques.SMAC 模拟物增强型三联双特异性 HIVxCD3 重定向分子在感染 SHIV.C.CH505、抗逆转录病毒治疗抑制的恒河猴中的作用。
J Virol. 2020 Oct 14;94(21). doi: 10.1128/JVI.00793-20.
6
Safety and Immunological Evaluation of Interleukin-21 Plus Anti-α4β7 mAb Combination Therapy in Rhesus Macaques.白细胞介素-21 联合抗 α4β7 mAb 组合疗法在恒河猴中的安全性和免疫原性评价。
Front Immunol. 2020 Jul 17;11:1275. doi: 10.3389/fimmu.2020.01275. eCollection 2020.
7
A Rare Mutation in an Infant-Derived HIV-1 Envelope Glycoprotein Alters Interprotomer Stability and Susceptibility to Broadly Neutralizing Antibodies Targeting the Trimer Apex.婴儿来源的 HIV-1 包膜糖蛋白中的一个罕见突变改变了二聚体间的稳定性，并影响了针对三聚体顶部的广谱中和抗体的敏感性。
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10
V2-Specific Antibodies in HIV-1 Vaccine Research and Natural Infection: Controllers or Surrogate Markers.HIV-1疫苗研究与自然感染中的V2特异性抗体：控制因素还是替代标志物
Vaccines (Basel). 2019 Aug 6;7(3):82. doi: 10.3390/vaccines7030082.
选择源自 HIV 和 SIV 感染和疫苗接种的 gp120 V2 结构域特异性抗体，抑制 gp120 与 α4β7 的结合。
PLoS Pathog. 2018 Aug 28;14(8):e1007278. doi: 10.1371/journal.ppat.1007278. eCollection 2018 Aug.
4
Importance of Fc-mediated functions of anti-HIV-1 broadly neutralizing antibodies.抗 HIV-1 广谱中和抗体 Fc 介导功能的重要性。
Retrovirology. 2018 Aug 22;15(1):58. doi: 10.1186/s12977-018-0438-x.
5
MAdCAM costimulation through Integrin-αβ promotes HIV replication.整合素-αβ通过黏附分子细胞间黏附分子共刺激促进 HIV 复制。
Mucosal Immunol. 2018 Sep;11(5):1342-1351. doi: 10.1038/s41385-018-0044-1. Epub 2018 Jun 6.
6
Potential of conventional & bispecific broadly neutralizing antibodies for prevention of HIV-1 subtype A, C & D infections.传统和双特异性广谱中和抗体预防 HIV-1 亚型 A、C 和 D 感染的潜力。
PLoS Pathog. 2018 Mar 5;14(3):e1006860. doi: 10.1371/journal.ppat.1006860. eCollection 2018 Mar.
7
Rational design of a trispecific antibody targeting the HIV-1 Env with elevated anti-viral activity.一种具有增强抗病毒活性的靶向HIV-1包膜糖蛋白的三特异性抗体的合理设计。
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8
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