Quaternized Cationic Carbon Dots as Antigen Delivery Systems for Improving Humoral and Cellular Immune Responses
Shaomei Huang, Bowen Li, Usama Ashraf, Qi Li, Xingchang Lu, Xiaochen Gao, Min Cui, Muhammad Imran, Jing Ye, Feifei Cao, Jiangjiang Gu, Shengbo Cao
Abstract
Adjuvant selection in vaccines is a key to induce potent immune responses. The current licensed adjuvant alum is found to be insufficient to induce cellular immune responses and a balanced Th1/Th2 ratio, which are desirable against cancers and microbial infections. Hence, it is encouraged to develop adjuvants which can simultaneously improve cell-mediated and humoral immune responses of the antigen and possess a favorable Th1/Th2 balance. Herein, quaternized cationic carbon dots derived from biquaternary ammonium salt (BQAS-CDs) were newly prepared, and their adjuvanticity and biocompatibility were preliminarily explored in vivo. The developed BQAS-CDs are enriched in quaternary ammonium groups on the surface, which enable them to bind to and aggregate with the negatively charged ovalbumin (OVA). The resulting BQAS-CDs + OVA nanocomplexes dramatically enhance the uptake of antigen by the antigen-presenting cells (APCs). Compared to the conventional adjuvant alum, the BQAS-CDs + OVA nanocomplexes significantly increase the anti-OVA IgG2a and IgG2b levels and keep the level of the OVA-specific IgG1 antibody, inducing both robust Th1- and Th2-type immune responses. Furthermore, they stimulate the proliferation of OVA-specific CD4+ and CD8+ T cells. No significant alterations were observed in the hematological and histological parameters of BQAS-CDs + OVA-immunized recipients. These findings suggest the potential benefits of BQAS-CDs as an alternative adjuvant in the future.