Incorporation of a GPI-anchored engineered cytokine as a molecular adjuvant enhances the immunogenicity of HIV VLPs.
Incorporation of a GPI-anchored engineered cytokine as a molecular adjuvant enhances the immunogenicity of HIV VLPs.
复制标题
DOI：
10.1038/srep11856
复制
发表时间：
2015-07-07
影响因子：
4.6
通讯作者：
Wang BZ
中科院分区：
文献类型：
--
作者：
Feng H;Zhang H;Deng J;Wang L;He Y;Wang S;Seyedtabaei R;Wang Q;Liu L;Galipeau J;Compans RW;Wang BZ
HIV疫苗应该在进入的粘膜入口处引起免疫应答以阻断传播，并在全身隔室引起免疫应答以清除传播的病毒。已经显示粘膜佐剂的共递送对于通过非复制型疫苗诱导有效的粘膜免疫是必不可少的。一种新的细胞因子，GIFT 4，融合GM-CSF和白细胞介素-4工程，以前发现模拟B细胞增殖和效应功能。本文通过融合糖脂（GPI）锚定序列构建GIFT 4的膜锚定形式，并将其掺入Env富集的HIV病毒样颗粒（VLP）中作为分子佐剂。通过肌内引发-鼻内加强免疫途径用所得HIV VLP免疫豚鼠。含有GIFT 4的VLP诱导更高水平的全身性抗体应答，具有显著增加的结合亲合力和改善的对一组选定菌株的中和宽度和效力，以及在几个粘膜部位的更高水平的IgG和伊加。因此，新的GPI-GIFT 4-containing VLP有可能被开发成一种预防性HIV疫苗。将GPI锚定的GIFT 4作为分子佐剂掺入VLP中代表了增加其免疫原性的新方法。
HIV vaccines should elicit immune responses at both the mucosal portals of entry to block transmission and systemic compartments to clear disseminated viruses. Co-delivery of mucosal adjuvants has been shown to be essential to induce effective mucosal immunity by non-replicating vaccines. A novel cytokine, GIFT4, engineered by fusing GM-CSF and interleukin-4, was previously found to simulate B cell proliferation and effector function. Herein a membrane-anchored form of GIFT4 was constructed by fusing a glycolipid (GPI)-anchoring sequence and incorporated into Env-enriched HIV virus-like particles (VLPs) as a molecular adjuvant. Guinea pigs were immunized with the resulting HIV VLPs through an intramuscular priming-intranasal boosting immunization route. The GIFT4-containing VLPs induced higher levels of systemic antibody responses with significantly increased binding avidity and improved neutralizing breadth and potency to a panel of selected strains, as well as higher levels of IgG and IgA at several mucosal sites. Thus, the novel GPI-GIFT4-containging VLPs have the potential to be developed into a prophylactic HIV vaccine. Incorporation of GPI-anchored GIFT4 into VLPs as a molecular adjuvant represents a novel approach to increase their immunogenicity.
登录
查看更多内容
影响因子：
4.4
作者：
Hedden SL;Whitaker D;Floyd L;Latimer WW
通讯作者：
Latimer WW
影响因子：
56.9
作者：
BARRESINOUSSI, F;CHERMANN, JC;MONTAGNIER, L
通讯作者：
MONTAGNIER, L
影响因子：
5.4
作者：
Barnett, Susan W.;Burke, Brian;Srivastava, Indresh K.
通讯作者：
Srivastava, Indresh K.
影响因子：
4.4
作者：
Alfsen, A;Iniguez, P;Bomsel, M
通讯作者：
Bomsel, M
HIV-1 疫苗功效试验的免疫相关分析。
DOI：
10.1056/nejmoa1113425
发表时间：
2012-04-05
期刊：
The New England journal of medicine
影响因子：
--
作者：
Haynes BF;Gilbert PB;McElrath MJ;Zolla-Pazner S;Tomaras GD;Alam SM;Evans DT;Montefiori DC;Karnasuta C;Sutthent R;Liao HX;DeVico AL;Lewis GK;Williams C;Pinter A;Fong Y;Janes H;DeCamp A;Huang Y;Rao M;Billings E;Karasavvas N;Robb ML;Ngauy V;de Souza MS;Paris R;Ferrari G;Bailer RT;Soderberg KA;Andrews C;Berman PW;Frahm N;De Rosa SC;Alpert MD;Yates NL;Shen X;Koup RA;Pitisuttithum P;Kaewkungwal J;Nitayaphan S;Rerks-Ngarm S;Michael NL;Kim JH
通讯作者：
Kim JH