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Injectable Hydrogels for Sustained Codelivery of Subunit Vaccines Enhance Humoral Immunity
ACS Central Science ( IF 18.2 ) Pub Date : 2020-09-16 , DOI: 10.1021/acscentsci.0c00732
Gillie A. Roth 1 , Emily C. Gale 2 , Marcela Alcántara-Hernández 3, 4 , Wei Luo 5 , Eneko Axpe 6 , Rohit Verma 5 , Qian Yin 5 , Anthony C. Yu 6 , Hector Lopez Hernandez 6 , Caitlin L. Maikawa 1 , Anton A. A. Smith 6 , Mark M. Davis 3, 4, 5, 7 , Bali Pulendran 3, 4, 5, 8, 9 , Juliana Idoyaga 3, 4, 5, 9 , Eric A. Appel 1, 5, 6, 9
Affiliation  

Vaccines aim to elicit a robust, yet targeted, immune response. Failure of a vaccine to elicit such a response arises in part from inappropriate temporal control over antigen and adjuvant presentation to the immune system. In this work, we sought to exploit the immune system’s natural response to extended pathogen exposure during infection by designing an easily administered slow-delivery vaccine platform. We utilized an injectable and self-healing polymer–nanoparticle (PNP) hydrogel platform to prolong the codelivery of vaccine components to the immune system. We demonstrated that these hydrogels exhibit unique delivery characteristics, whereby physicochemically distinct compounds (such as antigen and adjuvant) could be codelivered over the course of weeks. When administered in mice, hydrogel-based sustained vaccine exposure enhanced the magnitude, duration, and quality of the humoral immune response compared to standard PBS bolus administration of the same model vaccine. We report that the creation of a local inflammatory niche within the hydrogel, coupled with sustained exposure of vaccine cargo, enhanced the magnitude and duration of germinal center responses in the lymph nodes. This strengthened germinal center response promoted greater antibody affinity maturation, resulting in a more than 1000-fold increase in antigen-specific antibody affinity in comparison to bolus immunization. In summary, this work introduces a simple and effective vaccine delivery platform that increases the potency and durability of subunit vaccines.

中文翻译:

用于亚单位疫苗持续代孕的注射用水凝胶可增强体液免疫力

疫苗旨在引起强大而有针对性的免疫反应。疫苗未能引起这种反应的部分原因是由于对抗原的暂时性时间控制不当以及佐剂呈递给免疫系统。在这项工作中,我们试图通过设计易于管理的缓慢递送疫苗平台来开发免疫系统对感染过程中病原体暴露的自然反应。我们利用可注射且可自我修复的聚合物纳米颗粒(PNP)水凝胶平台来延长疫苗组分向免疫系统的传递。我们证明了这些水凝胶展现出独特的传递特性,从而可以在数周的时间内共传递物理化学上不同的化合物(例如抗原和佐剂)。当在小鼠体内给药时,与相同模型疫苗的标准PBS推注给药相比,基于水凝胶的持续疫苗暴露提高了体液免疫反应的强度,持续时间和质量。我们报告说,水凝胶内的局部炎性生态位的创建,加上持续暴露的疫苗货,增加了淋巴结中生发中心反应的幅度和持续时间。与推注免疫相比,这种增强的生发中心反应促进了更大的抗体亲和力成熟,从而导致抗原特异性抗体亲和力提高了1000倍以上。总之,这项工作引入了一种简单有效的疫苗输送平台,可提高亚单位疫苗的效力和耐用性。与标准PBS推注相同模型疫苗相比,体液免疫反应的质量和质量。我们报告说,水凝胶内的局部炎性生态位的创建,加上持续暴露的疫苗货,增加了淋巴结中生发中心反应的幅度和持续时间。与推注免疫相比,这种增强的生发中心反应促进了更大的抗体亲和力成熟,从而导致抗原特异性抗体亲和力提高了1000倍以上。总之,这项工作引入了一种简单有效的疫苗输送平台,可提高亚单位疫苗的效力和耐用性。与标准PBS推注相同模型疫苗相比,体液免疫反应的质量和质量。我们报告说,水凝胶内的局部炎性生态位的创建,加上持续暴露的疫苗货,增加了淋巴结中生发中心反应的幅度和持续时间。与推注免疫相比,这种增强的生发中心反应促进了更大的抗体亲和力成熟,从而导致抗原特异性抗体亲和力提高了1000倍以上。总而言之,这项工作引入了一个简单有效的疫苗输送平台,可提高亚单位疫苗的效力和耐用性。增强了淋巴结中生发中心反应的强度和持续时间。与推注免疫相比,这种增强的生发中心反应促进了更大的抗体亲和力成熟,从而导致抗原特异性抗体亲和力提高了1000倍以上。总之,这项工作引入了一种简单有效的疫苗输送平台,可提高亚单位疫苗的效力和耐用性。增强了淋巴结中生发中心反应的强度和持续时间。与推注免疫相比,这种增强的生发中心反应促进了更大的抗体亲和力成熟,从而导致抗原特异性抗体亲和力提高了1000倍以上。总之,这项工作引入了一种简单有效的疫苗输送平台,可提高亚单位疫苗的效力和耐用性。
更新日期:2020-10-29
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