Stephenson School of Biomedical Engineering, University of Oklahoma, Norman, OK, 73069, USA.
Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA.
Adv Sci (Weinh). 2022 Jul;9(21):e2105868. doi: 10.1002/advs.202105868. Epub 2022 May 22.
Immunogenic cell death (ICD) arises when cells are under stress, and their membranes are damaged. They release damage-associated molecular patterns (DAMPs) that stimulate and drive the type and magnitude of the immune response. In the presence of an antigen, DAMPs ride the longevity and efficacy of antigen-specific immunity. Yet, no tool can induce the controlled ICD with predictable results. A peptide-based tool, [II], is designed that aggregates in the cell and causes cell membrane damage, generates ICD and DAMPs release on various cell types, and hence can act as an adjuvant. An influenza vaccine is prepared by combining [II] with influenza hemagglutinin (HA) subunit antigens. The results show that [II] induced significantly higher HA-specific immunoglobulin G1 (IgG1) and IgG2a antibodies than HA-only immunized mice, while the peptide itself did not elicit antibodies. This paper demonstrates the first peptide-aggregation induced immunogenic rupture (PAIIR) approach as a vaccine adjuvant. PAIIR is a promising adjuvant with a high potential to promote universal protection upon influenza HA vaccination.
免疫原性细胞死亡 (ICD) 发生在细胞受到压力，其细胞膜受损时。它们释放损伤相关分子模式 (DAMPs)，刺激并驱动免疫反应的类型和幅度。在存在抗原的情况下，DAMPs 延长了抗原特异性免疫的持久性和效力。然而，没有一种工具可以诱导具有可预测结果的可控 ICD。设计了一种基于肽的工具 [II]，它在细胞中聚集并导致细胞膜损伤，在各种细胞类型上产生 ICD 和 DAMPs 释放，因此可以作为佐剂。流感疫苗通过将 [II] 与流感血凝素 (HA) 亚单位抗原结合制备。结果表明，[II] 诱导的 HA 特异性免疫球蛋白 G1 (IgG1) 和 IgG2a 抗体明显高于仅用 HA 免疫的小鼠，而肽本身并未引起抗体产生。本文首次证明了肽聚集诱导免疫破裂 (PAIIR) 作为疫苗佐剂的方法。PAIIR 是一种很有前途的佐剂，具有在流感 HA 疫苗接种时促进普遍保护的高潜力。
