High-throughput proteomic screening identifies Chlamydia trachomatis antigens that are capable of eliciting T cell and antibody responses that provide protection against vaginal challenge

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• 作者：Michele D. Picard^a ; Kenya Prince Cohane^a ; Todd M. Gierahn^a ; ¹ ; Darren E. Higgins^b ; Jessica Baker Flechtner^a ; ^{jessica.flechtner@genocea.com}
• 关键词：Chlamydia trachomatis ; T cell ; Protein antigens ; Vaccine
• 刊名：Vaccine
• 出版年：2012
• 期刊代码：89_0264410x
• 类别：imm
• 出版时间：19 June, 2012
• 卷：30
• 期：29
• 页码：4387-4393
• 文件大小：535 K

摘要

A comprehensive proteomic screening technology was previously used to characterize T cell responses to Chlamydia trachomatis infection. In this study, we demonstrated that T cells specific for protein antigens identified through this comprehensive technology home to the site of infection after mucosal challenge with C. trachomatis. In addition, T cell responses to these proteins were elicited in multiple genetic backgrounds. Two protein antigens, CT823 and CT144, were evaluated as vaccine candidates. When administered with AbISCO-100 adjuvant, these antigens stimulated potent CD8⁺ T cell responses, polyfunctional T_H1-polarized CD4⁺ T cell responses, and high titer protein-specific T_H1-skewed antibody responses. Vaccination with either antigen with AbISCO-100 provided long-lived protection against intravaginal challenge with C. trachomatis. Adoptive transfer of immune T cells also conferred protection in the challenge model whereas passive transfer of immune serum did not, indicating the critical role for T cell responses in control of this infection. The ability of these antigens to induce potent immune responses and provide long-lived protection in response to challenge provides a basis for the rational design of a C. trachomatis subunit vaccine.