Immunogenicity of a novel Clade B HIV-1 vaccine combination: Results of phase 1 randomized placebo controlled trial of an HIV-1 GM-CSF-expressing DNA prime with a modified vaccinia Ankara vaccine boost in healthy HIV-1 uninfected adults.
Immunogenicity of a novel Clade B HIV-1 vaccine combination: Results of phase 1 randomized placebo controlled trial of an HIV-1 GM-CSF-expressing DNA prime with a modified vaccinia Ankara vaccine boost in healthy HIV-1 uninfected adults.
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DOI：
10.1371/journal.pone.0179597
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
HIV Vaccine Trials Network (HVTN) 094 Study Group
中科院分区：
文献类型：
--
作者：
Buchbinder SP;Grunenberg NA;Sanchez BJ;Seaton KE;Ferrari G;Moody MA;Frahm N;Montefiori DC;Hay CM;Goepfert PA;Baden LR;Robinson HL;Yu X;Gilbert PB;McElrath MJ;Huang Y;Tomaras GD;HIV Vaccine Trials Network (HVTN) 094 Study Group
在未感染 HIV 的成人中进行的 B 分支 HIV 疫苗的 1 期试验评估了共表达 GM-CSF (Dg) 的 DNA Prime 的安全性和免疫原性，然后评估了不同数量和间隔的改良痘苗 Ankara Boosts (M)。两种疫苗都会产生呈现膜结合包膜的病毒样颗粒。美国四个研究中心将 48 名参与者随机分配到在第 0、2、4、6 和 8 个月时接受 1/10 DNA 剂量的 DgDgMMM，或分别在第 0、2、4 和 8 个月以及第 0、2、4、6 和 10 个月时接受全剂量 DgDgM_M 或 DgDgMM_M 方案。最后一次疫苗接种后 2 周测量峰值免疫原性。所有治疗方案均具有良好的耐受性且安全。全剂量 DgDgM_M 和 DgDgMM_M 方案在 >90% 的参与者中产生针对 HIV-1 Env 的 Env 特异性 IgG，在 >80% 的参与者中产生 IgG3，在 <20% 的参与者中产生 IgA。对 gp140 和 gp41 靶标的反应比对 gp120 和 V1V2 的反应更常见且程度更高。 gp41 抗体包括对保守免疫显性区域的反应性，该区域具有已知介导病毒捕获和吞噬作用的特异性，并且不与一组肠道菌群抗原发生交叉反应。第 3 剂 MVA 使引发抗体的亲合力增加（7.5% 至 39%）、对 Bal gp120 的 ADCC 反应（14% 至 64%）以及对 gp41 的 IgG3 反应的一年持久性增加了 4 倍（13% 与 3.5% 峰值反应保留率）。与不含 GM-CSF 的疫苗试验相比，共表达的 GM-CSF 并未增强反应。这种 DNA/MVA 初免-加强方案诱导持久的功能性体液反应，包括 ADCC、高抗体亲和力以及 Env IgG1 和 IgG3 对 gp41 免疫显性区域的结合反应。第三次间隔 MVA 增强提高了抗体反应的整体质量。这些没有共表达 GM-CSF 但与蛋白增强剂相结合的产品将被考虑用于功效评估。临床试验.gov NCT01571960
A phase 1 trial of a clade B HIV vaccine in HIV-uninfected adults evaluated the safety and immunogenicity of a DNA prime co-expressing GM-CSF (Dg) followed by different numbers and intervals of modified vaccinia Ankara Boosts (M). Both vaccines produce virus-like particles presenting membrane-bound Env. Four US sites randomized 48 participants to receiving 1/10th the DNA dose as DgDgMMM given at 0, 2, 4, 6 and 8 months, or full dose DgDgM_M or DgDgMM_M regimens, given at 0, 2, 4, and 8 months, and 0, 2, 4, 6, and 10 months, respectively. Peak immunogenicity was measured 2 weeks post-last vaccination. All regimens were well tolerated and safe. Full dose DgDgM_M and DgDgMM_M regimens generated Env-specific IgG to HIV-1 Env in >90%, IgG3 in >80%, and IgA in <20% of participants. Responses to gp140 and gp41 targets were more common and of higher magnitude than to gp120 and V1V2. The gp41 antibody included reactivity to the conserved immunodominant region with specificities known to mediate virus capture and phagocytosis and did not cross-react with a panel of intestinal flora antigens. The 3rd dose of MVA increased the avidity of elicited antibody (7.5% to 39%), the ADCC response to Bal gp120 (14% to 64%), and the one-year durability of the IgG3 responses to gp41 by 4-fold (13% vs. 3.5% retention of peak response). The co-expressed GM-CSF did not enhance responses over those in trials testing this vaccine without GM-CSF. This DNA/MVA prime-boost regimen induced durable, functional humoral responses that included ADCC, high antibody avidity, and Env IgG1 and IgG3 binding responses to the immunodominant region of gp41. The third, spaced MVA boost improved the overall quality of the antibody response. These products without co-expressed GM-CSF but combined with protein boosts will be considered for efficacy evaluation. ClinicalTrials.gov NCT01571960
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影响因子：
56.3
作者：
Gray, Glenda E.;Allen, Mai;Moodie, Zoe;Churchyard, Gavin;Bekker, Linda-Gail;Nchabeleng, Maphoshane;Mlisana, Koleka;Metch, Barbara;de Bruyn, Guy;Latka, Mary H.;Roux, Surita;Mathebula, Matsontso;Naicker, Nivashnee;Ducar, Constance;Carter, Donald K.;Puren, Adrien;Eaton, Niles;McElrath, M. Julie;Robertson, Michael;Corey, Lawrence;Kublin, James G.
通讯作者：
Kublin, James G.
影响因子：
3.7
作者：
Gottardo R;Bailer RT;Korber BT;Gnanakaran S;Phillips J;Shen X;Tomaras GD;Turk E;Imholte G;Eckler L;Wenschuh H;Zerweck J;Greene K;Gao H;Berman PW;Francis D;Sinangil F;Lee C;Nitayaphan S;Rerks-Ngarm S;Kaewkungwal J;Pitisuttithum P;Tartaglia J;Robb ML;Michael NL;Kim JH;Zolla-Pazner S;Haynes BF;Mascola JR;Self S;Gilbert P;Montefiori DC
通讯作者：
Montefiori DC
影响因子：
5.4
作者：
Gao, F;Weaver, EA;Haynes, BF
通讯作者：
Haynes, BF
影响因子：
1.8
作者：
Agresti, A;Coull, BA
通讯作者：
Coull, BA
影响因子：
4.2
作者：
Chamcha V;Kannanganat S;Gangadhara S;Nabi R;Kozlowski PA;Montefiori DC;LaBranche CC;Wrammert J;Keele BF;Balachandran H;Sahu S;Lifton M;Santra S;Basu R;Moss B;Robinson HL;Amara RR
通讯作者：
Amara RR