In addition to an antigen, many vaccines also contain substances, called adjuvants, which stimulate the immune system. Using computer-aided molecular design and machine learning, Bing Yan, Guangzhou University, China, Sijin Liu, Research Center for Eco-Environmental Sciences and University of Chinese Academy of Sciences, both Beijing, China, and Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China, and colleagues have developed two novel broad-spectrum adjuvants that can significantly amplify the immune response to vaccines. The team was able to enhance the effectiveness of immunization against certain forms of cancer in animal models.
Adjuvants with Broad-Spectrum Effectiveness
Adjuvants amplify and prolong the effect of vaccine immunizations. Aluminum salts have been successfully used as adjuvants for many decades. Alternatively, there are oil-in-water emulsions that target pattern recognition receptors on immune cells. However, older versions of this type of adjuvant were not effective enough or had troublesome side effects. Newer versions are well-tolerated and effective but need to be tailored for every individual vaccine.
The researchers have developed two novel adjuvants with broad-spectrum effectiveness that can significantly boost the immune response to vaccines. The new adjuvants are designed to bind to toll-like receptors (TLR), a class of proteins used by dendritic cells to detect the characteristic molecular patterns of pathogens. If an “enemy” is recognized, the dendritic cell moves into a lymph node and “presents” its find to the T-cells. These activated T-cells then multiply and enlist further immune cells in the fight.
Ligand Candidates Assembled on Au Nanoparticles
The team identified structural characteristics of the binding sites on human TLR and developed a substance library with 46 different ligands that are compatible with the binding site. The special twist in this case is that these ligands are anchored to the surfaces of biocompatible gold nanoparticles. This causes them to be bound more easily by the TLR. Two of the ligands were found to be especially effective. Comprehensive in vitro, ex vivo, and in vivo studies demonstrated that they bind to several different TLR and increase the activation of dendritic cells, presentation of antigens to T-cells, and their activation.
Mice treated with tumor-specific antigens plus one of these new adjuvants demonstrated strong immune responses that suppressed tumor growth and lung metastases after implantation of specific cancer cells.
Adjuvants further optimized through this method could reduce the problem of decreasing immunity for current vaccines and perhaps make booster vaccines unnecessary. Their use in immunotherapy to treat cancer is also highly promising.
- Computer‐Aided Discovery of Potent Broad‐Spectrum Vaccine Adjuvants,
Juan Ma, Shenqing Wang, Chuanfang Zhao, Xiliang Yan, Quanzhong Ren, Zheng Dong, Jiahuang Qiu, Yin Liu, Qing’e Shan, Ming Xu, Bing Yan, Sijin Liu,
Angew. Chem. Int. Ed. 2023.