Blocking α(4)β(7) integrin delays viral rebound in SHIV(SF162P3)-infected macaques treated with anti-HIV broadly neutralizing antibodies.
Blocking α(4)β(7) integrin delays viral rebound in SHIV(SF162P3)-infected macaques treated with anti-HIV broadly neutralizing antibodies.
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DOI：
10.1126/scitranslmed.abf7201
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发表时间：
2021-08-18
影响因子：
17.1
通讯作者：
Martinelli E
中科院分区：
文献类型：
--
作者：
Frank I;Cigoli M;Arif MS;Fahlberg MD;Maldonado S;Calenda G;Pegu A;Yang ES;Rawi R;Chuang GY;Geng H;Liu C;Zhou T;Kwong PD;Arthos J;Cicala C;Grasperge BF;Blanchard JL;Gettie A;Fennessey CM;Keele BF;Vaccari M;Hope TJ;Fauci AS;Mascola JR;Martinelli E
抗hiv广泛中和抗体（bNAbs）可能在免疫治疗过程中通过参与免疫系统而促进抗病毒免疫的发展。抗α4β7单克隆抗体（Rh-α4β7）靶向整合素α4β7影响SIV/ shiv感染猕猴的免疫应答。为了探索bNAbs联合α4β7整合素阻断剂的治疗潜力，我们将shivsf162p3感染的病毒血症恒河猴单独用bNAbs （VRC07-523LS和PGT128抗hiv抗体）或bNAbs与Rh-α4β7联合治疗或不治疗作为对照。在所有猕猴中，单独使用bNAbs治疗将病毒血症降低到200拷贝/ml以下，但仅使用bNAbs组的8只猕猴中有7只（87.5%）在中位3周内反弹（95% CI: 2至9）。相比之下，Rh-α4β7和bNAbs联合治疗的6只猕猴中有3只（50%）在随访结束前将病毒血症维持在200拷贝/ml以下；其他三只猕猴的病毒血症在6周内反弹（95%置信区间：5至11）。因此，与单独使用bnab相比，在接受联合抗体治疗的猕猴中，病毒反弹有适度的延迟。我们的研究表明α4β7整合素阻断可能延长了shivsf162p3感染猕猴的bnab病毒学控制。
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.
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影响因子：
4.6
作者：
Bankhead P;Loughrey MB;Fernández JA;Dombrowski Y;McArt DG;Dunne PD;McQuaid S;Gray RT;Murray LJ;Coleman HG;James JA;Salto-Tellez M;Hamilton PW
通讯作者：
Hamilton PW
影响因子：
64.8
作者：
Caskey M;Klein F;Lorenzi JC;Seaman MS;West AP Jr;Buckley N;Kremer G;Nogueira L;Braunschweig M;Scheid JF;Horwitz JA;Shimeliovich I;Ben-Avraham S;Witmer-Pack M;Platten M;Lehmann C;Burke LA;Hawthorne T;Gorelick RJ;Walker BD;Keler T;Gulick RM;Fätkenheuer G;Schlesinger SJ;Nussenzweig MC
通讯作者：
Nussenzweig MC
影响因子：
16.6
作者：
Francica, Joseph R.;Sheng, Zizhang;Zhang, Zhenhai;Nishimura, Yoshiaki;Shingai, Masashi;Ramesh, Akshaya;Keele, Brandon F.;Schmidt, Stephen D.;Flynn, Barbara J.;Darko, Sam;Lynch, Rebecca M.;Yamamoto, Takuya;Matus-Nicodemos, Rodrigo;Wolinsky, David;Nason, Martha;Valiante, Nicholas M.;Malyala, Padma;De Gregorio, Ennio;Barnett, Susan W.;Singh, Manmohan;O'Hagan, Derek T.;Koup, Richard A.;Mascola, John R.;Martin, Malcolm A.;Kepler, Thomas B.;Douek, Daniel C.;Shapiro, Lawrence;Seder, Robert A.
通讯作者：
Seder, Robert A.
影响因子：
64.8
作者：
通讯作者：
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影响因子：
5.4
作者：
Julg, Boris;Pegu, Amarendra;Barouch, Dan H.
通讯作者：
Barouch, Dan H.