The Shape of Nanostructures Encodes Immunomodulation of Carbohydrate Antigen and Vaccine Development

ACS Chem Biol. 2022 May 20;17(5):1122-1130. doi: 10.1021/acschembio.1c00998. Epub 2022 Apr 15.

Abstract

Gold nanoparticles (AuNPs) have shown remarkable potential for vaccine development, but the influence of the size and shape of nanoparticles modulating the T-cell-dependent carbohydrate antigen processing and immunomodulation is poorly investigated. Here, we described how different shapes and sizes of gold nanostructures carrying adjuvant modulate carbohydrate-based antigen processing in murine dendritic cells (mDCs) and subsequent T-cell activation produce a robust antibody response. As a prototype, CpG-adjuvant-coated spherical and rod- and star-shaped AuNPs were conjugated to the tripodal Tn-glycopeptide antigen to study their DC uptake and activation of T-cells in a DCs/T-cell co-culture assay. Our results showed that the spherical and star-shaped AuNPs displayed relatively weak receptor-mediated uptake and endosomal sequestration; however, they induced a high level of T helper-1 (Th1) biasing immune responses compared with rod-shaped AuNPs. Furthermore, the in vivo administration of AuNPs showed that the small spherical and star-shaped AuNPs induced an effective anti-Tn-glycopeptide immunoglobulin (IgG) antibody response compared with rod-shaped AuNPs. These results indicated that one could obtain superior carbohydrate vaccines by varying the shape and size parameters of nanostructures.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / pharmacology
  • Animals
  • Antigen Presentation
  • Carbohydrates
  • Dendritic Cells
  • Glycopeptides / pharmacology
  • Gold / chemistry
  • Immunomodulation
  • Metal Nanoparticles* / chemistry
  • Mice
  • Nanostructures*
  • Vaccine Development

Substances

  • Adjuvants, Immunologic
  • Carbohydrates
  • Glycopeptides
  • Gold