Siddoway Alaric C, White Brianna M, Narasimhan Balaji, Mallapragada Surya K
Department of Chemical & Biological Engineering, Iowa State University, Ames, IA 50011, USA.
Nanovaccine Institute, Ames, IA 50011, USA.
Vaccines (Basel). 2023 Oct 9;11(10):1572. doi: 10.3390/vaccines11101572.
Polymeric nanomaterials such as Pluronic-based pentablock copolymers offer important advantages over traditional vaccine adjuvants and have been increasingly investigated in an effort to develop more efficacious vaccines. Previous work with Pluronic F127-based pentablock copolymers, functionalized with poly(diethyl aminoethyl methacrylate) (PDEAEM) blocks, demonstrated adjuvant capabilities through the antigen presentation and crosslinking of B cell receptors. In this work, we describe the synthesis and optimization of a new family of low-molecular-weight Pluronic-based pentablock copolymer nanoadjuvants with high biocompatibility and improved adjuvanticity at low doses. We synthesized low-molecular-weight Pluronic P123-based pentablock copolymers with PDEAEM blocks and investigated the relationship between polymer concentration, micellar size, and zeta potential, and measured the release kinetics of a model antigen, ovalbumin, from these nanomaterials. The Pluronic P123-based pentablock copolymer nanoadjuvants showed higher biocompatibility than the first-generation Pluronic F127-based pentablock copolymer nanoadjuvants. We assessed the adjuvant capabilities of the ovalbumin-containing Pluronic P123-based pentablock copolymer-based nanovaccines in mice, and showed that animals immunized with these nanovaccines elicited high antibody titers, even when used at significantly reduced doses compared to Pluronic F127-based pentablock copolymers. Collectively, these studies demonstrate the synthesis, self-assembly, biocompatibility, and adjuvant properties of a new family of low-molecular-weight Pluronic P123-based pentablock copolymer nanomaterials, with the added benefits of more efficient renal clearance, high biocompatibility, and enhanced adjuvanticity at low polymer concentrations.
基于普朗尼克的五嵌段共聚物等聚合物纳米材料相较于传统疫苗佐剂具有重要优势，并且为了开发更有效的疫苗，人们对其研究越来越多。先前使用基于聚（甲基丙烯酸二乙氨基乙酯）（PDEAEM）嵌段功能化的普朗尼克F127五嵌段共聚物的研究表明，其通过抗原呈递和B细胞受体交联展现出佐剂能力。在这项工作中，我们描述了一类具有高生物相容性且在低剂量下具有改善佐剂性的新型低分子量基于普朗尼克的五嵌段共聚物纳米佐剂的合成与优化。我们合成了带有PDEAEM嵌段的低分子量基于普朗尼克P123的五嵌段共聚物，并研究了聚合物浓度、胶束尺寸和zeta电位之间的关系，还测量了模型抗原卵清蛋白从这些纳米材料中的释放动力学。基于普朗尼克P123的五嵌段共聚物纳米佐剂显示出比第一代基于普朗尼克F127的五嵌段共聚物纳米佐剂更高的生物相容性。我们评估了含卵清蛋白的基于普朗尼克P123的五嵌段共聚物纳米疫苗在小鼠体内的佐剂能力，结果表明，用这些纳米疫苗免疫的动物即使在与基于普朗尼克F127的五嵌段共聚物相比显著降低剂量的情况下也能引发高抗体滴度。总体而言，这些研究证明了一类新型低分子量基于普朗尼克P123的五嵌段共聚物纳米材料的合成、自组装、生物相容性和佐剂特性，其还具有更高效的肾脏清除、高生物相容性以及在低聚合物浓度下增强的佐剂性等额外优势。
