2. Academic Validation
  3. Incorporation of a Toll-like receptor 2/6 agonist potentiates mRNA vaccines against cancer and infectious diseases

Incorporation of a Toll-like receptor 2/6 agonist potentiates mRNA vaccines against cancer and infectious diseases

  • Signal Transduct Target Ther. 2023 Jul 17;8(1):273. doi: 10.1038/s41392-023-01479-4.
Yangzhuo Gu 1 2,  Jingyun Yang 3,  Cai He 3,  Tingmei Zhao 3,  Ran Lu 4,  Jian Liu 3,  Xianming Mo 4,  Fuqiang Wen 5,  Huashan Shi 6
Affiliations

Affiliations

  • 1 Department of Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan, 610041, China. yangzhuo_gu@163.com.
  • 2 Division of Pulmonary Diseases, State Key Laboratory of Biotherapy and Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China. yangzhuo_gu@163.com.
  • 3 Department of Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan, 610041, China.
  • 4 Laboratory of Stem Cell Biology and Department of Pediatric Surgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan, 610041, China.
  • 5 Division of Pulmonary Diseases, State Key Laboratory of Biotherapy and Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
  • 6 Department of Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan, 610041, China. shihuashan@scu.edu.cn.
PMID: 37455272 DOI: 10.1038/s41392-023-01479-4
Abstract

mRNA vaccines have emerged rapidly in recent years as a prophylactic and therapeutic agent against various diseases including Cancer and infectious diseases. Improvements of mRNA vaccines have been underway, among which boosting of efficacy is of great importance. Pam2Cys, a simple synthetic metabolizable lipoamino acid that signals through Toll-like Receptor (TLR) 2/6 pathway, eliciting both humoral and cellular adaptive immune responses, is an interesting candidate Adjuvant. To investigate the enhancement of the efficacies of mRNA vaccines by Pam2Cys, the Adjuvant was incorporated into mRNA-lipid nanoparticles (LNPs) to achieve co-delivery with mRNA. Immunization with the resulting mRNA-LNPs (Pam2Cys) shaped up the immune milieu in the draining lymph nodes (dLNs) through the induction of IL-12 and IL-17, among other cytokines. Antigen presentation was carried out mainly by migratory and dLN-resident conventional type 2 DCs (cDC2s) and significantly more potent antitumor responses were triggered in both prophylactic and therapeutic tumor models in a CD4+ and CD8+ T cell-dependent fashion. Accompanying memory antitumor immunity was also established. Moreover, the vaccine also stimulated much more robust humoral and cellular immunity in a surrogate COVID-19 prophylactic model. Last but not the least, the new vaccines exhibited good preliminary safety profiles in murine models. These facts warrant future development of Pam2Cys-incorporated mRNA vaccines or relevant mRNA therapeutics for clinical application.

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