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Blocking α4β7 integrin delays viral rebound in SHIVSF162P3-infected macaques treated with anti-HIV broadly neutralizing antibodies
Science Translational Medicine ( IF 15.8 ) Pub Date : 2021-08-18 , DOI: 10.1126/scitranslmed.abf7201
Ines Frank 1 , Mariasole Cigoli 1 , Muhammad S Arif 2 , Marissa D Fahlberg 3 , Stephanie Maldonado 1 , Giulia Calenda 1 , Amarendra Pegu 4 , Eun Sung Yang 4 , Reda Rawi 4 , Gwo-Yu Chuang 4 , Hui Geng 4 , Cuiping Liu 4 , Tongqing Zhou 4 , Peter D Kwong 4 , James Arthos 5 , Claudia Cicala 5 , Brooke F Grasperge 3 , James L Blanchard 3 , Agegnehu Gettie 6 , Christine M Fennessey 7 , Brandon F Keele 7 , Monica Vaccari 3 , Thomas J Hope 2 , Anthony S Fauci 5 , John R Mascola 4 , Elena Martinelli 1, 2
Affiliation  

Anti-HIV broadly neutralizing antibodies (bNAbs) may favor development of antiviral immunity by engaging the immune system during immunotherapy. Targeting integrin α4β7 with an anti-α4β7 monoclonal antibody (Rh-α4β7) affects immune responses in SIV/SHIV-infected macaques. To explore the therapeutic potential of combining bNAbs with α4β7 integrin blockade, SHIVSF162P3-infected, viremic rhesus macaques were treated with bNAbs only (VRC07-523LS and PGT128 anti-HIV antibodies) or a combination of bNAbs and Rh-α4β7 or were left untreated as a control. Treatment with bNAbs alone decreased viremia below 200 copies/ml in all macaques, but seven of eight macaques (87.5%) in the bNAbs-only group rebounded within a median of 3 weeks (95% CI: 2 to 9). In contrast, three of six macaques treated with a combination of Rh-α4β7 and bNAbs (50%) maintained a viremia below 200 copies/ml until the end of the follow-up period; viremia in the other three macaques rebounded within a median of 6 weeks (95% CI: 5 to 11). Thus, there was a modest delay in viral rebound in the macaques treated with the combination antibody therapy compared to bNAbs alone. Our study suggests that α4β7 integrin blockade may prolong virologic control by bNAbs in SHIVSF162P3-infected macaques.



中文翻译:


在接受抗 HIV 广泛中和抗体治疗的 SHIVSF162P3 感染猕猴中,阻断 α4β7 整合素可延迟病毒反弹



抗 HIV 广泛中和抗体 (bNAb) 可能通过在免疫治疗过程中激活免疫系统来促进抗病毒免疫的发展。使用抗 α 4 β 7单克隆抗体 (Rh-α 4 β 7 ) 靶向整合素 α 4 β 7会影响 SIV/SHIV 感染的猕猴的免疫反应。为了探索 bNAb 与 α 4 β 7整合素阻断相结合的治疗潜力,仅使用 bNAb(VRC07-523LS 和 PGT128 抗 HIV 抗体)或 bNAb 与 Rh-α 4组合治疗感染 SHIV SF162P3的病毒血症恒河猴。 β 7或未处理作为对照。单独使用 bNAb 治疗可将所有猕猴的病毒血症降至 200 拷贝/ml 以下,但仅使用 bNAb 组的八只猕猴中有七只 (87.5%) 在中位 3 周内出现反弹(95% CI:2 至 9)。相比之下,接受 Rh-α 4 β 7和 bNAb 联合治疗的 6 只猕猴中,有 3 只 (50%) 的病毒血症维持在 200 拷贝/ml 以下,直到随访期结束;其他三只猕猴的病毒血症在中位 6 周内反弹(95% CI:5 至 11)。因此,与单独使用 bNAb 相比,接受联合抗体疗法治疗的猕猴的病毒反弹略有延迟。我们的研究表明,在 SHIV SF162P3感染的猕猴中,α 4 β 7整合素阻断可能会延长 bNAb 的病毒学控制时间。

更新日期:2021-08-19
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