Targeting the R domain of coagulase by active vaccination protects mice against lethal Staphylococcus aureus infection |
| |
Authors: | Mengying Qian Taoran Zhao Ruihua Li Qiaoling Yang Rui Yu Ying Yin Xiaodong Zai Yaohui Li Jun Zhang Junjie Xu Wei Chen |
| |
Affiliation: | Laboratory of Vaccine and Antibody Engineering, Beijing Institute of Biotechnology, 20 Dongdajie Street, Fengtai District, Beijing 100071, China |
| |
Abstract: | Coagulase (Coa) secreted by Staphylococcus aureus is associated with the establishment of staphylococcal disease, which activates host prothrombin and generates fibrin shields. The R domain of Coa, consisting of several conserved repeats, is important in immune evasion during S. aureus infection. However, previous research showed that the Coa R domain induced very weak specific antibody responses. In this study, we constructed a new R domain, CoaR6, consisting of 6 repeats that occur most frequently in clinical isolates. By fusing CoaR6 with Hc, the C-terminal fragment of the heavy chain of tetanus neurotoxin, we successfully increased anti-CoaR6 IgG levels in immunized mice which were hardly detected in mice immunized with CoaR6 plus alum. To further improve anti-CoaR6 responses, the combination adjuvants alum plus CpG were formulated with the antigen and exhibited a significantly higher specific antibody response. Moreover, active Th1/Th17 immune responses were observed in Hc-CoaR6 immunized group rather than CoaR6. Active immunization of Hc-CoaR6 with alum plus CpG showed protective effects in a peritonitis model induced by two S. aureus strains with different coagulase types. Our results provided strategies to improve the immunogenicity of R domain and supporting evidences for R domain to be an S. aureus vaccine candidate. |
| |
Keywords: | Corresponding author. Vaccine Coagulase Immunogenicity |
本文献已被 ScienceDirect 等数据库收录! |
|