Development and Preliminary Mechanistic Evaluation of a Novel Liposomal QS-21 and CpG ODNs Adjuvant System for Enhancing Vaccine Immunogenicity.

Developing potent adjuvants is critical for enhancing vaccine efficacy, particularly for subunit antigens. Background/

Objectives

This study evaluates a novel composite adjuvant system combining liposomal QS-21 and CpG ODNs to enhance vaccine-induced immunogenicity, particularly Th1-type cellular immunity.

Methods

To mitigate QS-21's hemolytic toxicity and ensure precision delivery, a stable liposomal formulation was developed. Mice models were established using varicella-zoster virus (VZV) glycoprotein E (gE) or ovalbumin (OVA) as antigens to evaluate humoral and cellular immune responses.

Results

Immunization with gE protein formulated with this novel adjuvant synergistically triggered robust immune responses, outperforming single adjuvants and the combination of QS-21/MPL. Across broad dose ranges, it induced higher Th1-type cellular immunity and comparable humoral immunity relative to AS01B. Mechanistic studies revealed that the adjuvant significantly enhances the recruitment of dendritic cells (DCs), monocytes, and neutrophils to draining lymph nodes (dLNs) while upregulating co-stimulatory molecules CD40 and CD86 on DCs. Furthermore, the formulation triggered robust, transient increases in Th1-associated cytokines (IFN-γ, IL-12) and chemokines (CXCL9, CXCL10) across the injection site, serum, and dLNs.

Conclusions

These findings indicate that the liposomal QS-21 and CpG ODNs system is a highly effective platform for promoting robust Th1-biased immunity, offering a promising adjuvant candidate and a solid experimental foundation for developing next-generation vaccines requiring potent cellular immunity.