Large‐Sized Graphene Oxide Nanosheets Increase DC–T‐Cell Synaptic Contact and the Efficacy of DC Vaccines against SARS‐CoV‐2

• Published in: Advanced Materials 2021-10, Vol.33 (40), p.e2102528-n/a
• Main Authors: Zhou, Qianqian, Gu, Hongjing, Sun, Sujing, Zhang, Yulong, Hou, Yangyang, Li, Chenyan, Zhao, Yan, Ma, Ping, Lv, Liping, Aji, Subi, Sun, Shihui, Wang, Xiaohui, Zhan, Linsheng
• Format: Article
• Language: English
• Subjects: Adjuvants; Adjuvants, Immunologic - chemistry; Adjuvants, Immunologic - therapeutic use; Animals; COVID-19 - immunology; COVID-19 - prevention & control; COVID-19 Vaccines - immunology; COVID-19 Vaccines - therapeutic use; DC–T‐cell synapses; dendritic cells; Dendritic Cells - drug effects; Dendritic Cells - immunology; Graphene; Graphite - chemistry; Graphite - therapeutic use; Humans; ICAM‐1; Infectious diseases; Lymphocytes; Materials science; Mice; Nanomaterials; Nanosheets; Nanostructures - chemistry; Nanostructures - therapeutic use; SARS-CoV-2 - immunology; SARS‐CoV‐2; Severe acute respiratory syndrome coronavirus 2; Synapses; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; Vaccines
• ISSN: 0935-9648; 1521-4095; 1521-4095
• DOI: 10.1002/adma.202102528

Dendritic cell (DC) vaccines are used for cancer and infectious diseases, albeit with limited efficacy. Modulating the formation of DC–T‐cell synapses may greatly increase their efficacy. The effects of graphene oxide (GO) nanosheets on DCs and DC–T‐cell synapse formation are evaluated. In particular, size‐dependent interactions are observed between GO nanosheets and DCs. GOs with diameters of >1 µm (L‐GOs) demonstrate strong adherence to the DC surface, inducing cytoskeletal reorganization via the RhoA‐ROCK‐MLC pathway, while relatively small GOs (≈500 nm) are predominantly internalized by DCs. Furthermore, L‐GO treatment enhances DC–T‐cell synapse formation via cytoskeleton‐dependent membrane positioning of integrin ICAM‐1. L‐GO acts as a “nanozipper,” facilitating the aggregation of DC–T‐cell clusters to produce a stable microenvironment for T cell activation. Importantly, L‐GO‐adjuvanted DCs promote robust cytotoxic T cell immune responses against SARS‐CoV‐2 spike 1, leading to >99.7% viral RNA clearance in mice infected with a clinically isolated SARS‐CoV‐2 strain. These findings highlight the potential value of nanomaterials as DC vaccine adjuvants for modulating DC–T‐cell synapse formation and provide a basis for the development of effective COVID‐19 vaccines. A novel material‐based method of regulating dendritic cell (DC)–T‐cell synaptic contact for adoptive DC vaccine engineering is reported. Graphene oxide (GO) nanosheets serve as a “nanozipper” or “double‐sided tape” facilitating the formation and aggregation of DC–T‐cell immune synapses to elicit robust cytotoxic T cell immune responses against SARS‐CoV‐2 infection. Cytoskeleton‐dependent membrane‐positioning of intercellular cell adhesion molecule‐1 (ICAM‐1) might be the underlying mechanism.