Nanoparticle Shape Governs Immunomodulation of MUC1 Antigen to Develop Anti-cancer Vaccine

T-cell-dependent immunomodulation of carbohydrate antigens under benign conditions is the most promising approach for carbohydrate-based vaccine development. However, to achieve such adaptive immune responses, well-defined multifunctional nanocarriers loaded with immunogenic materials must be explor...

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Bibliographic Details
Published inbioRxiv
Main Authors Turaskar, Suraj, Preeti Madhukar Chaudhary, Raghavendra Kikkeri
Format Paper
LanguageEnglish
Published Cold Spring Harbor Cold Spring Harbor Laboratory Press 01.10.2021
Subjects
Adaptive immunity
Antibody response
Antigen processing
Antigens
Cancer vaccines
Carbohydrates
Cell activation
Cell culture
CpG islands
Dendritic cells
Glycopeptides
Immunogenicity
Immunoglobulin G
Immunomodulation
Lymphocytes T
MUC-1 antigen
Nanoparticles
Vaccine development
Vaccines
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Summary:T-cell-dependent immunomodulation of carbohydrate antigens under benign conditions is the most promising approach for carbohydrate-based vaccine development. However, to achieve such adaptive immune responses, well-defined multifunctional nanocarriers loaded with immunogenic materials must be explored. Current efforts to use gold nanoparticles (AuNPs) as antigen carriers in vaccine development have conveniently introduced considerable diversity. Here, we show that the shape of AuNPs markedly influences carbohydrate-based antigen processing in murine dendritic cells (mDCs) and subsequent T-cell activation. In the study, CpG-adjuvant coated sphere-, rod-, and star-shaped AuNPs were conjugated to the tripodal Tn-glycopeptide antigen to study their DC uptake and the activation of T-cells in the DCs/T-cell co-culture assay. Our results showed that sphere- and star-shaped AuNPs displayed relatively weak receptor-mediated uptake but induced a high level of T helper-1 (Th1) biasing immune responses compared with rod-shaped AuNPs, showing that receptor-mediated uptake and cytokine secretion of nanostructures are two independent mechanisms. Significantly, the shapes of AuNPs and antigen/adjuvant conjugation synergistically work together to modulate the effective anti-Tn-glycopeptide immunoglobulin (IgG) antibody response after in vivo administration of the AuNPs. These results show that by varying the shape parameter, one can alter the immunomodulation, leading to the development of carbohydrate vaccines. Competing Interest Statement The authors have declared no competing interest.
DOI:10.1101/2021.09.29.460739