Current efforts to develop novel vaccine nanotechnologies to increase cytotoxic T lymphocytes have met the challenges of the limited efficacy of antigen cross-presentation. Recent studies have uncovered a unique biological mechanism by which activation of the NADPH oxidase 2 (NOX2) complex, a major source of reactive oxygen species (ROS), enhances the cross-presentation by antigen-presenting cells (APCs). Inspired by the NOX2 mechanism, we devise biomineralized nanovaccines named NVs, which are developed by in situ growth of calcium peroxide on nanovaccines self-assembled with the model antigen ovalbumin. The ~80 nm NVs efficiently flow to the draining lymph nodes, where they accumulate within APC endo-/lysosomes, and generate a rapid burst of ROS in response to the acidic endo-/lysosomal environment with the subsequent endo-/lysosomal lipid peroxidation. Accompanied by the process, NVs stimulate distinct APCs maturation and antigen presentation to T lymphocytes. Notably, high levels of antigen-specific CD8 T cell responses, accompanied by the induction of CD4 T helper cells, are achieved. More importantly, NVs significantly increase the ratios of intratumoral CD8 T/regulatory T cells and achieve prominent tumor therapy effects. The NOX2-inspired biomineralized NVs represent an effective and easily applicable strategy that enables the strong cross-presentation of exogenous vaccine antigens.Copyright © 2021. Published by Elsevier Ltd.
About The Expert
Runping Su
Gaowei Chong
Haiqing Dong
Jingjing Gu
Jie Zang
Ruiqing He
Juanjuan Sun
Tingting Zhang
Yuge Zhao
Xiao Zheng
Yan Yang
Yan Li
Yongyong Li
References
PubMed