Department of Immunology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
Department of Polymer Chemistry, Graduate School of Engineering, Kyoto University, Kyoto, Japan.
Vaccine. 2021 Dec 20;39(52):7526-7530. doi: 10.1016/j.vaccine.2021.11.047. Epub 2021 Nov 29.
Carriers that augment delivery, immunogenicity or both are crucial in the development of vaccines especially component vaccines as components of pathogens are often poorly immunogenic. Cholesteryl pullulan (CHP) that forms nano-sized hydrogel (nanogel) and encapsulates proteins was shown to be useful in the delivery of vaccines. Here we demonstrate that subcutaneous immunization of mice with bovine serum albumin (BSA) chemically conjugated to NH-CHP nanogel induces strong antibody production. This augmented antibody production requires covalent conjugation between BSA and CHP, but does not require nanogel formation. Conjugation of NH-CHP nanogel induces persistence of BSA in dendritic cells (DCs) in vivo. As resistance to lysosomal degradation was previously shown to augment antigen presentation by DCs, conjugation of antigens with CHP nanogel may enhance antibody production to antigens by delaying lysosomal degradation. Therefore, delayed degradation of antigens by covalent conjugation with nanoparticles may be a good strategy for the development of effective vaccines.
载体可以增强递呈、免疫原性或两者兼具，在疫苗的开发中至关重要，特别是成分疫苗，因为病原体的成分通常免疫原性较差。胆固醇普鲁兰（CHP）可形成纳米级水凝胶（纳米凝胶）并包封蛋白质，已被证明可用于疫苗的递呈。在这里，我们证明了用化学偶联到 NH-CHP 纳米凝胶的牛血清白蛋白（BSA）对小鼠进行皮下免疫可诱导强烈的抗体产生。这种增强的抗体产生需要 BSA 和 CHP 之间的共价偶联，但不需要纳米凝胶形成。NH-CHP 纳米凝胶的偶联诱导 BSA 在体内树突状细胞（DC）中的持久性。由于先前已显示对溶酶体降解的抗性可增强 DC 的抗原呈递，因此用 CHP 纳米凝胶偶联抗原可能通过延迟溶酶体降解来增强针对抗原的抗体产生。因此，通过与纳米颗粒共价偶联来延迟抗原的降解可能是开发有效疫苗的一种好策略。
