2. Academic Validation
  3. Synergistic immune augmentation enabled by covalently conjugating TLR4 and NOD2 agonists

Synergistic immune augmentation enabled by covalently conjugating TLR4 and NOD2 agonists

  • Eur J Med Chem. 2024 Nov 15:278:116792. doi: 10.1016/j.ejmech.2024.116792.
Dong Ding 1,  Runing Gao 2,  Yujuan Lei 1,  Jianing Liu 2,  Chengkai Zhou 2,  Yu Wen 1,  Shihao Zhou 1,  Jun Guo 3,  Tiehai Li 4
Affiliations

Affiliations

  • 1 National Key Laboratory of Green Pesticide, International Joint Research Center for Intelligent Biosensing Technology and Health, College of Chemistry, Central China Normal University, Wuhan, 430079, China.
  • 2 State Key Laboratory of Chemical Biology, Carbohydrate-Based Drug Research Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
  • 3 National Key Laboratory of Green Pesticide, International Joint Research Center for Intelligent Biosensing Technology and Health, College of Chemistry, Central China Normal University, Wuhan, 430079, China. Electronic address: jguo@ccnu.edu.cn.
  • 4 State Key Laboratory of Chemical Biology, Carbohydrate-Based Drug Research Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China. Electronic address: tiehaili@simm.ac.cn.
PMID: 39217861 DOI: 10.1016/j.ejmech.2024.116792
Abstract

Enhancing the efficacy of subunit vaccines relies significantly on the utilization of potent adjuvants, particularly those capable of triggering multiple immune pathways. To achieve synergistic immune augmentation by Toll-like Receptor 4 agonist (TLR4a) and nucleotide-binding oligomerization-domain-containing protein 2 agonist (NOD2a), in this work, we conjugated RC529 (TLR4a) and MDP (NOD2a) to give RC529-MDP, and evaluated its adjuvanticity for OVA antigen. Compared to the unconjugated RC529+MDP, RC529-MDP remarkably enhanced innate immune responses with 6.8-fold increase in IL-6 cytokine, and promoted the maturation of antigen-presenting cells (APCs), possibly because of the conjugation of multiple agonists ensuring their delivery to the same cell and activation of various signaling pathways within that cell. Furthermore, RC529-MDP improved OVA-specific antibody response, T cells response and the memory T cells ratio relative to the unconjugated mixture. Therefore, covalently conjugating TLR4 Agonist and NOD2 agonist was an effective strategy to enhance immune responses, providing the potential to design and develop more effective vaccines.

Keywords

Adjuvant; Covalent conjugation; NOD2 agonist; Subunit vaccine; TLR4 agonist.

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