Development of Membrane Anchored Cytokines as Novel Vaccine Adjuvants for the Elderly

白细胞介素-12 （IL-12）和粒细胞巨噬细胞集落刺激因子（GM-CSF）是内源性免疫激活剂。早期使用可溶性IL-12和GM-CSF作为疫苗佐剂的研究由于毒性或次优反应而失败。Metaclipse治疗公司开发了在羧基端添加糖基化磷脂酰肌醇（GPI）锚点的IL-12和GM-CSF版本，允许将其结合到脂质双层中，如流感病毒样颗粒（VLPs）。先前在年轻和老年小鼠中使用GPI-GM-CSF和GPI-IL-12合并流感H1 VLPs的研究诱导了强大的体液和细胞免疫，保护年轻和老年小鼠免受同源和异源病毒的攻击。该SBIR项目将评估临床前动物模型的长期保护作用，并参与ind启用活动。目前，老年患者对流感疫苗反应不佳。该SBIR项目将有助于开发安全有效的佐剂组合，可用于提高老年人急需的流感和其他抗病毒疫苗的效力。

Interleukin-12 (IL-12) and granulocyte macrophage colony-stimulating factor (GM-CSF) are endogenous immune activators. Earlier studies using soluble IL-12 and GM-CSF as vaccine adjuvants were unsuccessful due to toxicity or suboptimal response. Metaclipse Therapeutic Corporation has developed versions of IL-12 and GM-CSF with a glycosylated phosphatidylinositol (GPI) anchor added at the carboxyl terminus, allowing incorporation into lipid bilayers such as in influenza virus-like particles (VLPs). Previous studies in young and aged mice using GPI-GM-CSF and GPI-IL-12 incorporated influenza H1 VLPs induced strong humoral and cellular immunity that protected both young and aged mice from homologous and heterologous viral challenge. This SBIR project will assess the long-term protection in preclinical animal models and engage in IND-enabling activities. Currently, elderly patients fail to respond well to influenza vaccines. This SBIR project will contribute to the development of safe and effective adjuvant combinations that can be used to enhance the efficacy of influenza and other antiviral vaccines critically needed for the elderly.