关键词: Antigen delivery platform Biomaterial Sustained release Vaccine platform

Mesh : Animals Spike Glycoprotein, Coronavirus / immunology Immunity, Humoral COVID-19 Vaccines / immunology administration & dosage Mice COVID-19 / prevention & control immunology Porosity Female Antibodies, Neutralizing / immunology Antibodies, Viral / immunology Biocompatible Materials / chemistry Mice, Inbred BALB C B-Lymphocytes / immunology SARS-CoV-2 / immunology Influenza Vaccines / immunology administration & dosage Mice, Inbred C57BL Orthomyxoviridae Infections / immunology prevention & control

来  源:   DOI:10.1016/j.jconrel.2024.05.008

Abstract:
Current antigen delivery platforms, such as alum and nanoparticles, are not readily tunable, thus may not generate optimal adaptive immune responses. We created an antigen delivery platform by loading lyophilized Microporous Annealed Particle (MAP) with aqueous solution containing target antigens. Upon administration of antigen loaded MAP (VaxMAP), the biomaterial reconstitution forms an instant antigen-loaded porous scaffold area with a sustained release profile to maximize humoral immunity. VaxMAP induced CD4+ T follicular helper (Tfh) cells and germinal center (GC) B cell responses in the lymph nodes similar to Alum. VaxMAP loaded with SARS-CoV-2 spike protein improved the magnitude, neutralization, and duration of anti-receptor binding domain antibodies compared to Alum vaccinated mice. A single injection of Influenza specific HA1-loaded-VaxMAP enhanced neutralizing antibodies and elicited greater protection against influenza virus challenge than HA1-loaded-Alum. Thus, VaxMAP is a platform that can be used to promote adaptive immune cell responses to generate more robust neutralizing antibodies, and better protection upon pathogen challenge.
摘要:
目前的抗原递送平台,如明矾和纳米粒子,不容易可调,因此可能不会产生最佳的适应性免疫反应。我们通过用含有靶抗原的水溶液装载冻干的微孔退火颗粒(MAP)来创建抗原递送平台。在施用抗原负载的MAP(VaxMAP)后,生物材料重建形成具有持续释放曲线的即时抗原负载多孔支架区域以最大化体液免疫。与明矾相似,VaxMAP诱导淋巴结中的CD4T滤泡辅助(Tfh)细胞和生发中心(GC)B细胞反应。负载SARS-CoV-2刺突蛋白的VaxMAP提高了幅度,中和,和抗受体结合结构域抗体与明矾疫苗接种小鼠相比的持续时间。与HA1负载明矾相比,单次注射流感特异性HA1负载VaxMAP增强了中和抗体,并引发了针对流感病毒攻击的更大保护。因此,VaxMAP是一个平台,可用于促进适应性免疫细胞反应,以产生更强大的中和抗体,以及更好的病原体攻击保护。
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