Immunodominance of Epitopes and Protective Efficacy of HI Antigen Are Differentially Altered Using Different Adjuvants in a Mouse Model of Staphylococcus aureus Bacteremia

Frontiers in Immunology

Xiaoli Zhang¹  Jiang Zhu²  Jintao Zou³  Qiang Gou³  Haiming Jing³  Hao Zeng³  Longlong Chen³  Zhuo Zhao³  Ping Luo³  Jinyong Zhang³  Quanming Zou³  Lianli Duan³  Yue Yuan³  Qingshan Xiong³  Zhifu Chen³ 

[1] Department of Clinical Hematology, College of Pharmacy, Third Military Medical University, Chongqing, China;Department of Pathology, Southwest Hospital, Third Military Medical University, Chongqing, China;National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing, China;

关键词: Staphylococcus aureus;    immunodominant epitope;    antibody;    adjuvants;    bacteremia;   

DOI  :  10.3389/fimmu.2021.684823

来源: DOAJ

【 摘 要 】

HI, a fusion protein that consists of the alpha-toxin (Hla) and the N2 domain of iron surface determinant B (IsdB), is one of the antigens in the previously reported S. aureus vaccine rFSAV and has already entered phase II clinical trials. Previous studies revealed that HI is highly immunogenic in both mice and healthy volunteers, and the humoral immune response plays key roles in HI-mediated protection. In this study, we further investigated the protective efficacy of immunization with HI plus four different adjuvants in a mouse bacteremia model. Results showed that HI-mediated protection was altered in response to different adjuvants. Using antisera from immunized mice, we identified seven B-cell immunodominant epitopes on Hla and IsdB, including 6 novel epitopes (Hla1-18, Hla84-101, Hla186-203, IsdB342-359, IsdB366-383, and IsdB384-401). The immunodominance of B-cell epitopes, total IgG titers and the levels of IFN-γ and IL-17A from mice immunized with HI plus different adjuvants were different from each other, which may explain the difference in protective immunity observed in each immunized group. Thus, our results indicate that adjuvants largely affected the immunodominance of epitopes and the protective efficacy of HI, which may guide further adjuvant screening for vaccine development and optimization.

【 授权许可】

Unknown