Rationally Designed TLR2-QS-21 Liposomal Adjuvant Enhances Immunogenicity while Reducing Reactogenicity in Subunit Vaccines.

Authors

Wei Ma, Renpeng Tang, Hong Wang, Hongbin Jia, Yuping Wang, Shijun Zhou, Tinghong Lv, Xiaolei Wang

Published in

Journal of medicinal chemistry. Volume 69. Issue 21. Pages 26580-26594. Nov 12, 2026.

Abstract

Potent vaccine adjuvants often link strong adaptive immunity with excessive inflammation. Here, we developed BQS01, a liposomal adjuvant that replaces the TLR4 agonist monophosphoryl lipid A (MPL) with a synthetic TLR2 agonist (BXY-14) while retaining QS-21. BQS01 induced a TLR2-associated transcriptional profile, enhanced dendritic cell activation and T-cell priming, and was associated with increased IL-10 production. In ovalbumin and varicella-zoster virus mouse models, BQS01 generated antibody responses comparable to an AS01b-like MPL/QS-21 comparator and durable polyfunctional cellular immunity, while reducing systemic weight loss, local inflammation, and TNF-α accumulation. These findings suggest that innate signaling architecture, rather than inflammatory magnitude alone, contributes to adjuvant performance and may guide the design of next-generation vaccines with an improved immunogenicity-reactogenicity balance.

PMID:
43018625
Bibliographic data and abstract were imported from PubMed on 12 Nov 2026.

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