Immunodominance of Epitopes and Protective Efficacy of HI Antigen Are Differentially Altered Using Different Adjuvants in a Mouse Model of Staphylococcus aureus Bacteremia.
Immunodominance of Epitopes and Protective Efficacy of HI Antigen Are Differentially Altered Using Different Adjuvants in a Mouse Model of Staphylococcus aureus Bacteremia.
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DOI：
10.3389/fimmu.2021.684823
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发表时间：
2021
影响因子：
7.3
通讯作者：
Zhang J
中科院分区：
文献类型：
--
作者：
Chen Z;Gou Q;Xiong Q;Duan L;Yuan Y;Zhu J;Zou J;Chen L;Jing H;Zhang X;Luo P;Zeng H;Zou Q;Zhao Z;Zhang J
HI是金黄色葡萄球菌疫苗rFSAV的抗原之一，由α-毒素(Hla)和铁表面决定簇B(ISDB)的n2结构域组成，已进入II期临床试验。以往的研究表明，HI在小鼠和健康志愿者中都具有高度的免疫原性，体液免疫反应在HI介导的保护中起着关键作用。在这项研究中，我们进一步研究了HI加四种不同佐剂免疫小鼠菌血症模型的保护效果。结果表明，HI介导的保护作用因不同佐剂的不同而发生改变。利用免疫小鼠的抗血清，我们鉴定了7个B细胞免疫优势表位，其中包括6个新表位(Hla1-18、Hla84-101、Hla186-203、IsdB342-359、IsdB366-383和IsdB384-401)。HI加不同佐剂免疫小鼠的B细胞表位、总Ig G滴度、干扰素-γ和IL-17A水平的免疫优势不同，这可能解释了各免疫组保护性免疫的差异。因此，我们的结果表明佐剂在很大程度上影响了表位的免疫优势和HI的保护效果，这可能为疫苗开发和优化进一步的佐剂筛选提供指导。
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.
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