Viral-vectored boosting of OmcB- or CPAF-specific T-cell responses fail to enhance protection from Chlamydia muridarum in infection-immune mice and elicits a non-protective CD8-dominant response in naïve mice

IF 7.9 2区 医学 Q1 IMMUNOLOGY
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Abstract

A vaccine is needed to combat the Chlamydia epidemic. Replication-deficient viral vectors are safe and induce antigen-specific T-cell memory. We tested the ability of intramuscular immunization with modified vaccinia Ankara (MVA) virus or chimpanzee adenovirus (ChAd) expressing chlamydial outer membrane protein (OmcB) or the secreted protein, chlamydial protease-like activating factor (CPAF), to enhance T-cell immunity and protection in mice previously infected with plasmid-deficient Chlamydia muridarum CM972 and elicit protection in naïve mice. MVA.OmcB or MVA.CPAF increased antigen-specific T cells in CM972-immune mice ∼150 and 50-fold, respectively, but failed to improve bacterial clearance. ChAd.OmcB/MVA.OmcB prime-boost immunization of naïve mice elicited a cluster of differentiation (CD) 8-dominant T-cell response dominated by cluster of differentiation (CD)8 T cells that failed to protect. ChAd.CPAF/ChAd.CPAF prime-boost also induced a CD8-dominant response with a marginal reduction in burden. Challenge of ChAd.CPAF-immunized mice genetically deficient in CD4 or CD8 T cells showed that protection was entirely CD4-dependent. CD4-deficient mice had prolonged infection, whereas CD8-deficient mice had higher frequencies of CPAF-specific CD4 T cells, earlier clearance, and reduced burden than wild-type controls. These data reinforce the essential nature of the CD4 T-cell response in protection from chlamydial genital infection in mice and the need for vaccine platforms that drive CD4-dominant responses.
病毒载体增强的 OmcB 或 CPAF 特异性 T 细胞反应不能增强感染免疫小鼠对鼠衣原体的保护能力,并在幼稚小鼠中引起无保护作用的 CD8 优势反应。
需要一种疫苗来防治衣原体流行病。复制缺陷病毒载体既安全又能诱导抗原特异性 T 细胞记忆。我们测试了用表达衣原体外膜蛋白OmcB或分泌蛋白CPAF的改良安卡拉疫苗病毒(MVA)或黑猩猩腺病毒(ChAd)进行肌肉注射免疫,增强小鼠T细胞免疫力和保护力的能力,这些小鼠以前感染过质粒缺陷的鼠衣原体CM972,并在天真小鼠中产生保护作用。MVA.OmcB 或 MVA.CPAF 可使 CM972-免疫小鼠的抗原特异性 T 细胞分别增加 150 倍和 50 倍,但未能提高细菌清除率。ChAd.OmcB/MVA.OmcB对幼稚小鼠的原代增强免疫引起了CD8占优势的T细胞反应,但未能起到保护作用。ChAd.CPAF/ChAd.CPAF原代增强免疫也能诱导CD8优势反应,但负担略有减少。对基因上缺乏 CD4 或 CD8 T 细胞的 ChAd.CPAF 免疫小鼠的挑战表明,保护作用完全依赖于 CD4。与野生型对照组相比,CD4缺陷小鼠的感染时间延长,而CD8缺陷小鼠的CPAF特异性CD4 T细胞频率更高,清除时间更早,负担更轻。这些数据进一步证实了 CD4 T 细胞应答在保护小鼠免受衣原体生殖器感染中的重要作用,同时也证明了开发 CD4 主导应答的疫苗平台的必要性。
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来源期刊
Mucosal Immunology
Mucosal Immunology 医学-免疫学
CiteScore
16.60
自引率
3.80%
发文量
100
审稿时长
12 days
期刊介绍: Mucosal Immunology, the official publication of the Society of Mucosal Immunology (SMI), serves as a forum for both basic and clinical scientists to discuss immunity and inflammation involving mucosal tissues. It covers gastrointestinal, pulmonary, nasopharyngeal, oral, ocular, and genitourinary immunology through original research articles, scholarly reviews, commentaries, editorials, and letters. The journal gives equal consideration to basic, translational, and clinical studies and also serves as a primary communication channel for the SMI governing board and its members, featuring society news, meeting announcements, policy discussions, and job/training opportunities advertisements.
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