PDF(Pubmed)
Abstract：
Vaccines represent a pivotal health advancement for preventing infection. However, because carrier systems with repeated administration can invoke carrier-targeted immune responses that diminish subsequent immune responses (e.g., PEG antibodies), there is a continual need to develop novel vaccine platforms. Zinc carnosine microparticles (ZnCar MPs), which are composed of a one-dimensional coordination polymer formed between carnosine and the metal ion zinc, have exhibited efficacy in inducing an immune response against influenza. However, ZnCar MPs\' limited suspendability hinders clinical application. In this study, we address this issue by mixing mannan, a polysaccharide derived from yeast, with ZnCar MPs. We show that the addition of mannan increases the suspendability of this promising vaccine formulation. Additionally, since mannan is an adjuvant, we illustrate that the addition of mannan increases the antibody response and T cell response when mixed with ZnCar MPs. Mice vaccinated with mannan + OVA/ZnCar MPs had elevated serum IgG and IgG1 levels in comparison to vaccination without mannan. Moreover, in the mannan + OVA/ZnCar MPs vaccinated group, mucosal washes demonstrated increased IgG, IgG1, and IgG2c titers, and antigen recall assays showed enhanced IFN-γ production in response to MHC-I and MHC-II immunodominant peptide restimulation, compared to the vaccination without mannan. These findings suggest that the use of mannan mixed with ZnCar MPs holds potential for subunit vaccination and its improved suspendability further promotes clinical translation.
摘要：
疫苗代表着预防感染的关键健康进步。然而,因为重复给药的载体系统可以引起靶向载体的免疫反应，从而减少随后的免疫反应（例如，PEG抗体），不断需要开发新的疫苗平台.肌肽锌微粒(ZnCarMPs)，它们由肌肽和金属离子锌之间形成的一维配位聚合物组成，在诱导针对流感的免疫应答方面表现出功效。然而,ZnCarMPs有限的悬吊性阻碍了临床应用。在这项研究中,我们通过混合甘露聚糖来解决这个问题，一种来自酵母的多糖，与ZnCarMP。我们表明，甘露聚糖的添加增加了这种有前途的疫苗制剂的悬浮性。此外,因为甘露聚糖是一种佐剂,我们说明，当与ZnCarMPs混合时，添加甘露聚糖会增加抗体应答和T细胞应答。与没有甘露聚糖的接种相比,用甘露聚糖+OVA/ZnCarMPs接种的小鼠具有升高的血清IgG和IgG1水平。此外，在甘露聚糖+OVA/ZnCarMPs疫苗接种组中，粘膜洗液显示IgG增加，IgG1和IgG2c滴度，和抗原召回分析显示增强的IFN-γ产生响应MHC-I和MHC-II免疫优势肽再刺激，与没有甘露聚糖的疫苗相比。这些发现表明，使用甘露聚糖与ZnCarMPs混合具有亚单位疫苗接种的潜力，其改善的悬浮性进一步促进了临床翻译。
