期刊
VACCINE
卷 31, 期 2, 页码 313-318出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.vaccine.2012.11.008
关键词
Acinetobacter baumannii; OmpA; Vaccine; Type 1/Type 2 immunity; Epitope spreading
资金
- PHS [R01 AI081719]
- Veterans Affairs Merit Review Program
- National Institutes of Health [RO1AI063517, RO1AI072219]
- VISN 10 Geriatric Research Education and Clinical Center (GRECC)
Background: The rOmpA vaccine has been shown to protect mice from lethal infection caused by extreme-drug-resistant (XDR) Acinetobacter baumannii. The role of dose in immunology of the rOmpA vaccine was explored. Methods: Mice were vaccinated with various doses of rOmpA plus aluminum hydroxide (Al(OH)(3)) adjuvant. The impact of dose on antibody titers, cytokine production, and immunodominant epitopes was defined. Results: Anti-rOmpA IgG and IgG subtype titers were higher at larger vaccine doses (30 and 100 mu g vs. 3 mu g). The 3 mu g dose induced a balanced IFN-gamma-IL-4 immune response while the 100 mu g dose induced a polarized IL-4/Type 2 response. Epitope mapping revealed distinct T cell epitopes that activated IFN-gamma-, IL-4-, and IL-17-producing splenocytes. Vaccination with the 100 mu g dose caused epitope spreading among IL-4-producing splenocytes, while it induced fewer reactive epitopes among IFN-gamma-producing splenocytes. Conclusions: Vaccine dose escalation resulted in an enhanced Type 2 immune response, accompanied by substantial IL-4-inducing T cell epitope spreading and restricted IFN-gamma-inducing epitopes. These results inform continued development of the rOmpA vaccine against A. baumannii, and also are of general importance in that they indicate that immune polarization and epitope selectivity can be modulated by altering vaccine dose. (C) 2012 Elsevier Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据