Vaccine Adjuvant/ Delivery Systems Core

新的佐剂/递送策略可以使蛋白质和多肽疫苗同时诱导有效的细胞 体液免疫将极大地补充艾滋病毒疫苗开发的现有方法。 在这个核心，我们将供应和进一步开发两类最近开发的有效新型佐剂 欧文实验室将支持项目1和项目2的亚单位疫苗研究，以研究人类免疫 BLT人源化小鼠对HIV免疫原的反应：稳定的脂质纳米胶囊(SLNC)和 膜靶向胶束(MTM)。SLNC是一种脂质纳米胶囊系统，用于运送蛋白质或 多肽抗原和分子危险信号，如TLR激动剂(TLRa)，它们保留 包埋抗原/TLRa比传统脂质体更有效，导致增强 抗原/佐剂向树突状细胞递送和引流淋巴结中抗原的持续积聚 在接种疫苗后。第二种佐剂系统，膜靶向胶束(MTM)，是基于 分子佐剂或多肽抗原与形成胶束的脂尾的结合。这些 两亲性分子在水中自组装形成直径15纳米的纳米颗粒，但也是动态的 当与细胞接触时，解体将其脂尾固定在膜中。MTMS戏剧性地瞄准 TLRa或多肽进入淋巴结，形成结内疫苗仓库。注射，和驾驶 强烈增强对联合注射蛋白抗原的免疫反应。我们将提供这些强大的 项目1和2的BLT人源化小鼠免疫研究需要佐剂。此外，我们 将进一步开发这些佐剂，以最大限度地提高BLT小鼠的有效性，同时设计的佐剂可以忽略不计 毒性/反应性，以确保它们与人类疫苗开发的相关性。这些研究的结果 将进一步将BLT人源化小鼠模型作为疫苗开发的工具，通过识别有效的 疫苗接种佐剂和给药途径，并提供适用于多种疾病的新佐剂 艾滋病毒以外的亚单位疫苗。

New adjuvant/delivery strategies that could enable protein and peptide vaccines to elicit both potent cellular and humoral immunity would be highly complementary to existing approaches in HIV vaccine development. In this Core, we will supply and further develop two classes of potent novel adjuvants recently developed in the Irvine lab to support the subunit vaccine studies of projects 1 and 2 in studying human immune responses to HIV immunogens in BLT humanized mice: stabilized lipid nanocapsules (SLNCs) and membrane-targeted micelles (MTMs). SLNCs are a lipid nanocapsule system for delivery of protein or peptide antigens together with molecular danger signals such as TLR agonists (TLRa), which retain entrapped antigen/TLRa much more effectively than traditional liposomes, leading to enhanced antigen/adjuvant delivery to dendritic cells and sustained accumulation of antigen in draining lymph nodes following vaccination. The second adjuvant system, membrane-targeted micelles (MTM), is based on the conjugation of molecular adjuvants or peptide antigen cargos to a micelle-forming lipid tail. These amphiphilic molecules self-assemble to form nanoparticles -15 nm in diameter in water, but also dynamically dis-assemble to anchor their lipid tails in the membrane on contact with cells. MTMs dramatically target TLRa or peptides to lymph nodes, forming intranodal vaccine depots following s.c. injection, and driving strongly enhanced immune responses to co-administered protein antigens. We will provide these potent adjuvants on demand for BLT humanized mouse immunization studies for projects 1 and 2. In addition, we will further develop these adjuvants to maximize the effectiveness in BLT mice while designing for negligible toxicity/reactogenicity, to ensure their relevance for human vaccine development. Results from these studies will further the BLT humanized mouse model as a tool for vaccine development, by identifying effective adjuvants and routes of administration for vaccine delivery, and provide new adjuvants applicable to diverse subunit vaccines beyond HIV.