Potent functional antibody responses elicited by HIV-I DNA priming and boosting with heterologous HIV-1 recombinant MVA in healthy Tanzanian adults.
Potent functional antibody responses elicited by HIV-I DNA priming and boosting with heterologous HIV-1 recombinant MVA in healthy Tanzanian adults.
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DOI：
10.1371/journal.pone.0118486
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Polonis VR
中科院分区：
文献类型：
--
作者：
Joachim A;Nilsson C;Aboud S;Bakari M;Lyamuya EF;Robb ML;Marovich MA;Earl P;Moss B;Ochsenbauer C;Wahren B;Mhalu F;Sandström E;Biberfeld G;Ferrari G;Polonis VR
在从参与I/II期安慰剂对照双盲试验的健康坦桑尼亚志愿者中采集的血清样品中评价疫苗诱导的HIV抗体，该试验使用多进化枝、多基因HIV-DNA引发和重组改良安卡拉牛痘（HIV-MVA）病毒加强（HIVIS 03）。HIV-DNA疫苗含有表达HIV-1 gp 160 A、B、C、Rev B、Gag A、B和RTmut B亚型的质粒，重组HIV-MVA加强免疫表达CRF 01_AE HIV-1 Env E亚型和Gag-Pol A亚型。虽然在TZM-bl细胞测定中使用假病毒没有检测到中和抗体，但是当使用荧光素酶抑制剂感染性分子克隆（LucR-IMC）进行外周血单核细胞（PBMC）测定时，这种初免-加强疫苗接种在83%的HIVIS 03疫苗接种者中诱导中和抗体。PBMC中自然杀伤（NK）细胞耗竭后，血清中和活性显著（但不完全）降低（p=0.006），表明抗体介导的Fcγ受体功能发挥作用。随后在97%的疫苗接种者血清中证实了高水平的抗体依赖性细胞毒性（ADCC）介导的抗CRF 01_AE和/或亚型B抗体。在IMC/PBMC试验中，针对CM 235 CRF01_AE IMC感染细胞的ADCC介导抗体的大小与针对CM 235的中和抗体相关。总之，HIV-DNA引发，然后两次HIV-MVA加强，在很大一部分坦桑尼亚疫苗接种者中引起了有效的ADCC反应。我们的研究结果强调了HIV-DNA初免HIV-MVA加强疫苗诱导功能性抗体应答的潜力，并表明这种疫苗方案和ADCC研究是HIV疫苗开发的潜在重要新途径。对照试验ISRCTN 90053831泛非临床试验登记研究ATMR 2009040001075080（目前为PACTR 2009040001075080）
Vaccine-induced HIV antibodies were evaluated in serum samples collected from healthy Tanzanian volunteers participating in a phase I/II placebo-controlled double blind trial using multi-clade, multigene HIV-DNA priming and recombinant modified vaccinia Ankara (HIV-MVA) virus boosting (HIVIS03). The HIV-DNA vaccine contained plasmids expressing HIV-1 gp160 subtypes A, B, C, Rev B, Gag A, B and RTmut B, and the recombinant HIV-MVA boost expressed CRF01_AE HIV-1 Env subtype E and Gag-Pol subtype A. While no neutralizing antibodies were detected using pseudoviruses in the TZM-bl cell assay, this prime-boost vaccination induced neutralizing antibodies in 83% of HIVIS03 vaccinees when a peripheral blood mononuclear cell (PBMC) assay using luciferase reporter-infectious molecular clones (LucR-IMC) was employed. The serum neutralizing activity was significantly (but not completely) reduced upon depletion of natural killer (NK) cells from PBMC (p=0.006), indicating a role for antibody-mediated Fcγ-receptor function. High levels of antibody-dependent cellular cytotoxicity (ADCC)-mediating antibodies against CRF01_AE and/or subtype B were subsequently demonstrated in 97% of the sera of vaccinees. The magnitude of ADCC-mediating antibodies against CM235 CRF01_AE IMC-infected cells correlated with neutralizing antibodies against CM235 in the IMC/PBMC assay. In conclusion, HIV-DNA priming, followed by two HIV-MVA boosts elicited potent ADCC responses in a high proportion of Tanzanian vaccinees. Our findings highlight the potential of HIV-DNA prime HIV-MVA boost vaccines for induction of functional antibody responses and suggest this vaccine regimen and ADCC studies as potentially important new avenues in HIV vaccine development. Controlled-Trials ISRCTN90053831 The Pan African Clinical Trials Registry ATMR2009040001075080 (currently PACTR2009040001075080)
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影响因子：
3.7
作者：
Edmonds TG;Ding H;Yuan X;Wei Q;Smith KS;Conway JA;Wieczorek L;Brown B;Polonis V;West JT;Montefiori DC;Kappes JC;Ochsenbauer C
通讯作者：
Ochsenbauer C
影响因子：
3.7
作者：
Lambotte O;Pollara J;Boufassa F;Moog C;Venet A;Haynes BF;Delfraissy JF;Saez-Cirion A;Ferrari G
通讯作者：
Ferrari G
影响因子：
5.4
作者：
Hessell, Ann J.;Rakasz, Eva G.;Burton, Dennis R.
通讯作者：
Burton, Dennis R.
DOI：
10.1073/pnas.1217609110
发表时间：
2013-01-02
影响因子：
11.1
作者：
Guan, Yongjun;Pazgier, Marzena;Lewis, George K.
通讯作者：
Lewis, George K.
影响因子：
5.4
作者：
Hidajat, Rachmat;Xiao, Peng;Robert-Guroff, Marjorie
通讯作者：
Robert-Guroff, Marjorie