Institute for Bioscience and Biotechnology Research, University of Maryland, Rockville, MD, United States.
Cancer ImmunoPrevention Laboratory, Frederick National Laboratory for Cancer Research, Frederick, MD, United States.
Nanomedicine. 2021 Apr;33:102359. doi: 10.1016/j.nano.2021.102359. Epub 2021 Jan 18.
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 a 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.
聚[双（羧甲基苯氧基）磷腈]（PCMP）是聚磷腈免疫佐剂家族的新成员，现已合成。对一种新的大分子的体外评估显示，其水解降解谱和免疫刺激活性与临床阶段同源物 PCPP 相当；然而，PCMP 的特点是对离子环境的敏感性降低。基于人乳头瘤病毒（HPV）病毒样颗粒（VLPs）的 RG1-VLPs 疫苗对 PCMP 效力进行了体内评估。与先前报道的聚磷腈佐剂与蛋白质的自组装形成多聚体展示抗原的复合物不同，PCMP 以依赖于组成的方式表面修饰 VLPs，在高聚合物与 VLPs 的比例下导致抗原性颗粒的稳定。在小鼠中的免疫实验表明，PCMP 佐剂的 RG1-VLPs 疫苗诱导了强烈的体液免疫应答，特别是在高度理想的保护性交叉中和抗体水平上，优于 PCPP 和 Alhydrogel 佐剂制剂。
