A GLYCOLIPID ADJUVANT 7DW8-5 FOR MALARIA VACCINES

该合同项目的目标是开发人类使用的以糖脂为基础的佐剂，具有疟疾疫苗的初步适应症。我们的产品开发项目的范围是开发我们的新型CD1d结合的自然杀伤T(NKT)细胞刺激糖脂，称为7DW8-5，作为一种多功能疫苗佐剂。最初的合作伙伴疫苗是以核酸为基础的启动疫苗和以全寄生虫为基础的以肝脏为靶标的增强疟疾疫苗。我们已经发表了7DW8-5糖脂在小鼠模型中显著提高核酸原虫诱捕型疟疾疫苗的免疫原性和效力，并有更多的数据表明这种佐剂简化了疫苗的配制和给药。在这里，我们将对非GMP级7DW8-5的配方、溶解性、释放度、稳定性和毒理学进行评估。我们还将确认7DW8-5/疟疾疫苗在非人类灵长类动物(NHP)中的安全性、免疫原性和有效性。最后，我们将为未来的7DW8-5 FDA审查制定IND前的监管包。

The goal of this contract project is to develop the glycolipid-based adjuvant for human use, with initial indications for a malaria vaccine. The scope of our product development project is to develop our novel CD1d-binding natural killer T (NKT) cell-stimulatory glycolipid, called 7DW8-5, as a versatile vaccine adjuvant. Initial partner vaccines are based on a nucleic acid-based priming and whole parasite-based boosting liver-targeted malaria vaccine. We have published that that the 7DW8-5 glycolipid significantly increases the immunogenicity and efficacy of the nucleic acid prime-and-parasite trap malaria vaccines in a mouse model and have additional data showing that the adjuvant simplifies formulation and administration of this vaccine. Here, we will evaluate non-GMP-grade 7DW8-5 for formulation, solubility, release, stability, and toxicology. We will also confirm safety, immunogenicity, and efficacy of the 7DW8-5/malaria vaccine in non-human primates (NHPs). Lastly, we will develop a pre-IND regulatory package for future 7DW8-5 FDA review.