A Toll-like Receptor-Activating, Self-Adjuvant Glycan Nanocarrier

Daping Xie; Yiming Niu; Ruoyu Mu; Senio Campos de Souza; Xiaoyu Yin; Lei Dong; Chunming Wang

doi:10.3389/fchem.2022.864206

A Toll-like Receptor-Activating, Self-Adjuvant Glycan Nanocarrier

Front Chem. 2022 May 3:10:864206. doi: 10.3389/fchem.2022.864206. eCollection 2022.

Authors

Daping Xie¹, Yiming Niu¹, Ruoyu Mu¹, Senio Campos de Souza¹, Xiaoyu Yin^{1

2}, Lei Dong², Chunming Wang¹

Affiliations

¹ State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao SAR, China.
² State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China.

Abstract

The global pandemic of COVID-19 highlights the importance of vaccination, which remains the most efficient measure against many diseases. Despite the progress in vaccine design, concerns with suboptimal antigen immunogenicity and delivery efficiency prevail. Self-adjuvant carriers-vehicles that can simultaneously deliver antigens and act as adjuvants-may improve efficacies in these aspects. Here, we developed a self-adjuvant carrier based on an acetyl glucomannan (acGM), which can activate toll-like receptor 2 (TLR2) and encapsulate the model antigen ovalbumin (OVA) via a double-emulsion process. In vitro tests showed that these OVA@acGM-8k nanoparticles (NPs) enhanced cellular uptake and activated TLR2 on the surface of dendritic cells (DCs), with increased expression of co-stimulatory molecules (e.g. CD80 and CD86) and pro-inflammatory cytokines (e.g. TNF-α and IL12p70). In vivo experiments in mice demonstrated that OVA@acGM-8k NPs accumulated in the lymph nodes and promoted DCs' maturation. The immunization also boosted the humoral and cellular immune responses. Our findings suggest that this self-adjuvant polysaccharide carrier could be a promising approach for vaccine development.

Keywords: glucomannan; polysaccharides; self-adjuvant; toll-like receptors; vaccination.