Large-Sized Graphene Oxide Nanosheets Increase DC-T-Cell Synaptic Contact and the Efficacy of DC Vaccines against SARS-CoV-2.
Adv Mater
; 33(40): e2102528, 2021 Oct.
Article
in English
| MEDLINE | ID: covidwho-1358054
ABSTRACT
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.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Dendritic Cells
/
Adjuvants, Immunologic
/
Nanostructures
/
COVID-19 Vaccines
/
COVID-19
/
Graphite
Type of study:
Experimental Studies
/
Prognostic study
Topics:
Vaccines
Limits:
Animals
/
Humans
Language:
English
Journal:
Adv Mater
Journal subject:
Biophysics
/
Chemistry
Year:
2021
Document Type:
Article
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