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首页> 外文期刊>Vaccine >Systemic immunization with CCL27/CTACK modulates immune responses at mucosal sites in mice and macaques.
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Systemic immunization with CCL27/CTACK modulates immune responses at mucosal sites in mice and macaques.

机译：CCL27 / CTACK的全身免疫调节小鼠和猕猴黏膜部位的免疫反应。

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摘要

Plasmid DNA is a promising vaccine platform that has been shown to be safe and able to be administered repeatedly without vector interference. Enhancing the potency of DNA vaccination through co-delivery of molecular adjuvants is one strategy currently under investigation. Here we describe the use of the novel chemokine adjuvant CCL27/CTACK to enhance immune responses to an HIV-1 or SIV antigen in mice and rhesus macaques. CCL27 has been shown to play a role in inflammatory responses through chemotaxis of CCR10+ cells, and we hypothesized that CCL27 may modulate adaptive immune responses. Immunizations in mice with HIV-1gag/CCL27 enhanced immune responses both at peripheral and, surprisingly, at mucosal sites. To confirm these findings in a large-animal model, we created optimized CCL27 and SIV antigenic plasmid constructs for rhesus macaques. 10 macaques (n=5/group) were immunized intramuscularly with 1 mg/construct of antigenic plasmids+or-CCL27 with electroporation. We observed significant IFN- gamma secretion and CD8+ T-cell proliferation in peripheral blood. Interestingly, CCL27 co-immunized macaques exhibited a trend toward greater effector CD4+ T cells in the bronchiolar lavage (BAL). CCL27 co-delivery also elicited greater antigen-specific IgA at unique sites including BAL and fecal samples but not in the periphery. Future studies incorporating CCL27 as an adjuvant in vaccine or therapy models where eliciting immune responses in the lung are warranted.
机译：质粒DNA是一种有前途的疫苗平台，已被证明是安全的，能够在不干扰载体的情况下重复施用。通过共同递送分子佐剂来增强DNA疫苗接种的效力是目前正在研究的一种策略。在这里，我们描述了新型趋化因子佐剂CCL27 / CTACK在小鼠和恒河猴中增强对HIV-1或SIV抗原的免疫应答的用途。已显示CCL27通过CCR10 +细胞的趋化性在炎症反应中发挥作用，我们假设CCL27可能调节适应性免疫反应。用HIV-1gag / CCL27进行的小鼠免疫增强了外周和粘膜部位的免疫反应。为了在大型动物模型中证实这些发现，我们为猕猴创建了优化的CCL27和SIV抗原质粒构建体。用1mg /构建的抗原质粒+或-​​CCL27通过电穿孔肌内免疫10只猕猴（n ＝ 5 /组）。我们观察到外周血中明显的IFN-γ分泌和CD8 + T细胞增殖。有趣的是，CCL27共同免疫的猕猴在细支气管灌洗（BAL）中表现出趋向于效应CD4 + T细胞的趋势。 CCL27共递送还在包括BAL和粪便样品在内的独特位点而非周边产生了更大的抗原特异性IgA。将来有必要在疫苗或治疗模型中纳入CCL27作为佐剂，以确保在肺中引起免疫反应。

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