Center for Immunity and Inflammation, Rutgers New Jersey Medical School, Newark, NJ 07103, United States of America.
Tempo Therapeutics, 3030 Bunker Hill st., suite 104, San Diego, CA 92109, United States of America.
J Control Release. 2024 Jun;370:570-582. doi: 10.1016/j.jconrel.2024.05.008. Epub 2024 May 11.
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.
目前的抗原递送平台,如铝佐剂和纳米颗粒,不易调节,因此可能无法产生最佳的适应性免疫反应。我们通过将冻干的微孔退火颗粒(MAP)加载到含有目标抗原的水溶液中,创建了一种抗原递送平台。在给予负载抗原的 MAP(VaxMAP)后,生物材料重构形成具有持续释放特征的即时抗原负载多孔支架区域,以最大限度地提高体液免疫。VaxMAP 在淋巴结中诱导 CD4 滤泡辅助(Tfh)细胞和生发中心(GC)B 细胞反应,类似于铝佐剂。与接种铝佐剂的小鼠相比,负载 SARS-CoV-2 刺突蛋白的 VaxMAP 提高了抗体的效价、中和作用和持续时间。单次注射流感特异性 HA1 负载-VaxMAP 可增强中和抗体,并对流感病毒攻击产生更好的保护作用,优于 HA1 负载的铝佐剂。因此,VaxMAP 是一种可以用来促进适应性免疫细胞反应的平台,以产生更强大的中和抗体,并在病原体攻击时提供更好的保护。
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