Molecular engineering and plant expression of an immunoglobulin heavy chain scaffold for delivery of a dengue vaccine candidate.
Molecular engineering and plant expression of an immunoglobulin heavy chain scaffold for delivery of a dengue vaccine candidate.
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DOI：
10.1111/pbi.12741
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发表时间：
2017-12
影响因子：
13.8
通讯作者：
Ma JK
中科院分区：
文献类型：
--
作者：
Kim MY;Van Dolleweerd C;Copland A;Paul MJ;Hofmann S;Webster GR;Julik E;Ceballos-Olvera I;Reyes-Del Valle J;Yang MS;Jang YS;Reljic R;Ma JK
为了增强体内免疫细胞对疫苗的摄取，采用分子工程方法构建了一种聚合免疫球蛋白G支架（猪），该支架包含抗原的多个拷贝，并靶向抗原呈递细胞上的Fc γ受体。这些自我佐剂免疫原在登革热感染的背景下进行了测试，目前还没有全球许可的登革热疫苗。因此，登革糖蛋白E的共识结构域III序列（cEDIII）被纳入猪，并在烟草和中国子房仓鼠细胞中表达。纯化的小鼠和人cEDIII‐猪通过高效液相色谱分离成低分子量和高分子量形式，分别对应于单体、二聚体和聚合物。cEDIII‐猪被证明保留了与免疫球蛋白相关的重要Fc受体功能，包括与补体的C1q组分和低亲和力Fcγ受体II结合，以及在体外与巨噬细胞结合。这些分子在小鼠中显示出免疫原性，无论是否有佐剂，诱导高水平的IgG抗体反应，显示出对2型登革热病毒的中和潜力。cEDIII‐猪也诱导了显著的细胞免疫应答、IFN‐γ的产生和CD4+和CD8+区室的多功能T细胞。这项原理验证研究表明，有效的抗体Fc介导的细胞功能可用于改进疫苗设计，强调了该技术诱导和调节广泛免疫反应的潜力。
In order to enhance vaccine uptake by the immune cells in vivo, molecular engineering approach was employed to construct a polymeric immunoglobulin G scaffold (PIGS) that incorporates multiple copies of an antigen and targets the Fc gamma receptors on antigen‐presenting cells. These self‐adjuvanting immunogens were tested in the context of dengue infection, for which there is currently no globally licensed vaccine yet. Thus, the consensus domain III sequence (cEDIII) of dengue glycoprotein E was incorporated into PIGS and expressed in both tobacco plants and Chinese Ovary Hamster cells. Purified mouse and human cEDIII‐PIGS were fractionated by HPLC into low and high molecular weight forms, corresponding to monomers, dimers and polymers. cEDIII‐PIGS were shown to retain important Fc receptor functions associated with immunoglobulins, including binding to C1q component of the complement and the low affinity Fcγ receptor II, as well as to macrophage cells in vitro. These molecules were shown to be immunogenic in mice, with or without an adjuvant, inducing a high level IgG antibody response which showed a neutralizing potential against the dengue virus serotype 2. The cEDIII‐PIGS also induced a significant cellular immune response, IFN‐γ production and polyfunctional T cells in both the CD4+ and CD8+ compartments. This proof‐of‐principle study shows that the potent antibody Fc‐mediated cellular functions can be harnessed to improve vaccine design, underscoring the potential of this technology to induce and modulate a broad‐ranging immune response.
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影响因子：
6.7
作者：
Balsitis SJ;Williams KL;Lachica R;Flores D;Kyle JL;Mehlhop E;Johnson S;Diamond MS;Beatty PR;Harris E
通讯作者：
Harris E
影响因子：
5.5
作者：
Govindarajan, Dhanasekaran;Meschino, Steven;Bett, Andrew J.
通讯作者：
Bett, Andrew J.
影响因子：
5.5
作者：
Guy, Bruno;Barrere, Beatrice;Lang, Jean
通讯作者：
Lang, Jean
影响因子：
5.5
作者：
Chiang, Chen-Yi;Hsieh, Chun-Hsiang;Chen, Hsin-Wei
通讯作者：
Chen, Hsin-Wei
影响因子：
158.5
作者：
Hadinegoro, S. R.;Arredondo-Garcia, J. L.;Saville, M.
通讯作者：
Saville, M.