Effects of small molecule compounds combined with aluminum adjuvant on the protective efficacy of candidate antigen PA0833 from Pseudomonas aeruginosa and the underlying mechanisms
10.3760/cma.j.cn112309-20231129-00157
- VernacularTitle:小分子化合物与铝佐剂联用对铜绿假单胞菌疫苗候选抗原PA0833保护效果的影响及机制初步研究
- Author:
Tianjun SUN
1
;
Xiaoli ZHANG
;
Zhenping XIA
;
Zhuo ZHAO
;
Jinyong ZHANG
;
Yi WANG
Author Information
1. 中国海洋大学医药学院，海洋药物教育部重点实验室，青岛 266003
- Keywords:
Adjuvant;
Sodium diethyldithiocarbamate (DTC);
Pseudomonas aeruginosa;
Vaccine
- From:
Chinese Journal of Microbiology and Immunology
2024;44(3):189-197
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To evaluate the impact of three small compounds, namely sodium diethyldithiocarbamate (DTC), levamisole (LMS) and imiquimod (Imi), on the immunogenicity and protective efficacy of the candidate antigen PA0833 from Pseudomonas aeruginosa ( Pa) and analyze the underlying mechanisms. Methods:PA0833 was formulated with aluminum adjuvant and the above small compounds, respectively. BALB/c mice were immunized with these vaccines intramuscularly on days 0, 14 and 21. Serum samples were collected and the levels of PA0833-specific IgG were measured by ELISA. The protective efficacy of these vaccines was evaluated by assessment of survival rates, body weights, clinical scores, inflammatory factors, and histopathological changes after infecting the immunized mice with Pa PAO1 strains. Besides, the mice were injected with DTC intramuscularly for seven consecutive days to analyze the mechanism of DTC in enhancing immune response using transcriptome sequencing and flow cytometry. Results:All these small compounds were capable of effectively enhancing the immunogenicity of PA0833 formulated with aluminum adjuvant, reducing bacterial loads in lung tissues, inhibiting the secretion of TNF-α, IL-6 and IL-1β, and improving mouse survival rates upon Pa infection. DTC was more effective than the other two compounds. Transcriptome sequencing identified 121 up-regulated genes and 18 down-regulated genes in DTC-treated group as compared with PBS control group. These differentially expressed genes were significantly enriched in immune pathways, with a strong activation of the IL-17 pathway. Flow cytometry analysis demonstrated significant activation of dendritic cells and proliferation of Th17 cells in splenocytes in DTC-treated group as compared with PBS control group. Conclusions:All three small compounds are able of effectively enhance antigen immunogenicity with DTC being the most effective, indicating that DTC can be used as a novel adjuvant in vaccine development.
