Next generation polyphosphazene immunoadjuvant: Synthesis, self-assembly and in vivo potency with human papillomavirus VLPs-based vaccine.
Next generation polyphosphazene immunoadjuvant: Synthesis, self-assembly and in vivo potency with human papillomavirus VLPs-based vaccine.
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新一代多磷腈免疫佐剂：合成、自组装和人乳头瘤病毒vlps疫苗的体内效力。
DOI：
10.1016/j.nano.2021.102359
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发表时间：
2021-04
期刊：
影响因子：
--
通讯作者：
Andrianov AK
中科院分区：
文献类型：
--
作者：
Marin A;Chowdhury A;Valencia SM;Zacharia A;Kirnbauer R;Roden RBS;Pinto LA;Shoemaker RH;Marshall JD;Andrianov AK
合成了聚磷腈免疫佐剂家族的新成员--聚[二（羧甲基苯氧基）磷腈]（PCMP）.一种新的大分子的体外评估显示其水解降解特征和免疫刺激活性与其临床阶段同系物- PCPP相当，然而PCMP的特征在于对离子环境的敏感性降低。使用基于人乳头瘤病毒（HPV）病毒样颗粒（VLP）的RG 1-VLP疫苗进行PCMP效力的体内评价。与先前报道的聚磷腈佐剂与蛋白质的自组装（其通常导致形成具有抗原的多聚体展示的复合物）相比，PCMP以组合物依赖性模式表面修饰VLP，其在高聚合物与VLP比率下导致抗原颗粒的稳定化。在小鼠中的免疫实验证明，PCMP佐剂化的RG 1-VLP疫苗诱导有效的体液免疫应答，特别是在高度期望的保护性交叉中和抗体的水平上，并且优于PCPP和铝胶佐剂化的制剂。设计、合成并表征了一种新型生物可降解聚磷腈免疫佐剂（PCMP）。用基于人乳头瘤病毒（HPV）病毒样颗粒（VLP）的疫苗评价其效力。当配制在一起时，PCMP以组合物依赖性图案在VLP表面上自组装，导致分散或聚集的纳米结构，其尺寸超过单个组分的尺寸。在体内，含PCMP佐剂的疫苗优于其他测试制剂，特别是在诱导高度期望的保护性交叉中和抗体方面。
Poly[di(carboxylatomethylphenoxy)phosphazene], PCMP - a new member of polyphosphazene immunoadjuvant family is synthesized. In vitro assessment of a new macromolecule revealed hydrolytic degradation profile and immunostimulatory activity comparable to its clinical stage homologue - PCPP, however PCMP was characterized by a beneficial reduced sensitivity to the ionic environment. In vivo evaluation of PCMP potency was conducted with Human Papillomavirus (HPV) virus-like particles (VLPs) based RG1-VLPs vaccine. In contrast with previously reported self-assembly of polyphosphazene adjuvants with proteins, which typically results in the formation of complexes with multimeric display of antigens, PCMP surface modified VLPs in the composition dependent pattern, which at a high polymer-to VLPs ratio led to stabilization of antigenic particles. Immunization experiments in mice demonstrated that PCMP adjuvanted RG1-VLPs vaccine induced potent humoral immune responses, in particular, on the level of highly desirable protective cross-neutralizing antibodies, and outperformed PCPP and Alhydrogel adjuvanted formulations. Novel biodegradable polyphosphazene immunoadjuvant (PCMP) was designed, synthesized, and characterized. Its potency was evaluated with Human Papillomavirus (HPV) virus-like particles (VLPs) based vaccine. When formulated together, PCMP self-assembled on the surface of VLPs in a composition-dependent pattern resulting in dispersed or aggregated nanostructures with dimensions, which exceeded the size of individual components. In vivo, PCMP adjuvanted vaccine outperforms other tested formulations, especially in the induction of highly desirable protective cross-neutralizing antibodies.
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影响因子：
4
作者：
Andrianov AK;Marin A;Fuerst TR
通讯作者：
Fuerst TR
影响因子：
7.6
作者：
Ison MG;Mills J;Openshaw P;Zambon M;Osterhaus A;Hayden F
通讯作者：
Hayden F
影响因子：
6.2
作者：
Andrianov, AK;Marin, A;Chen, JP
通讯作者：
Chen, JP
影响因子：
16.6
作者：
Grimme, Stefan
通讯作者：
Grimme, Stefan
影响因子：
1.8
作者：
Dar, Arshud;Lai, Ken;Mutwiri, George K.
通讯作者：
Mutwiri, George K.