Abstract B143: Lace molecular vaccine with adjuvant booster to enhance immunogenicity

Chunsong Yu, Haipeng Liu
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Abstract

Manipulation of vaccine adjuvants, including bioconjugation and particle formulation, is a prevailing approach to achieve efficient delivery and improve therapeutic efficacy. However, these approaches may compromise bioactivity or may not be desirable when these compounds are chemically or physically unmanipulable. Here, we report an “adjuvant booster” strategy to markedly promote immunogenicity by simply lacing molecular vaccines with an adjuvant booster. We created an adjuvant booster, lipid modified 20-mer thymidine oligodeoxynucleotide (lipo T20), which could significantly increase the potency of Toll-like receptor 7 (TLR7) ligands in both murine and human TLR7 HEK 293 cells and substantially target draining lymph nodes where unmodified adjuvant rarely accumulated. Subcutaneous administration of “imiquimod/protein antigen” vaccine laced with lipo T20 in mice resulted in a five-fold increase in T-cell priming and enhanced antibody response in comparison to booster-free vaccine. “Adjuvant booster” strategy provides an alternative and simple methodology to further enhance immunogenicity of molecular vaccines. Citation Format: Chunson Yu, Haipeng Liu. Lace molecular vaccine with adjuvant booster to enhance immunogenicity [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B143.
B143:蕾丝分子疫苗加佐剂增强免疫原性
操纵疫苗佐剂,包括生物偶联和颗粒配方,是实现有效递送和提高治疗效果的普遍方法。然而,当这些化合物在化学上或物理上无法操作时,这些方法可能会损害生物活性或可能不可取。在这里,我们报告了一种“佐剂增强剂”策略,通过简单地将分子疫苗与佐剂增强剂结合,显着提高免疫原性。我们创造了一种佐剂增强剂,脂质修饰的20聚胸苷寡脱氧核苷酸(lipo T20),它可以显著提高toll样受体7 (TLR7)配体在小鼠和人TLR7 HEK 293细胞中的效力,并且基本上靶向未修饰佐剂很少积聚的引流淋巴结。在小鼠中皮下注射含有脂质T20的“咪喹莫特/蛋白抗原”疫苗,与无增强剂疫苗相比,t细胞启动和抗体反应增加了5倍。“佐剂增强”策略为进一步提高分子疫苗的免疫原性提供了一种简单的替代方法。引文格式:于春森,刘海鹏。分子疫苗加佐剂增强免疫原性[摘要]。第四届CRI-CIMT-EATI-AACR国际癌症免疫治疗会议:将科学转化为生存;2018年9月30日至10月3日;纽约,纽约。费城(PA): AACR;癌症免疫学杂志2019;7(2增刊):摘要nr B143。
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