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一种多阴离子型 Carbomer 诱导针对 HIV-1 gp140 和流感病毒 HA 的强烈适应性免疫应答。

Potent adaptive immune responses induced against HIV-1 gp140 and influenza virus HA by a polyanionic carbomer.

机构信息

The Sir William Dunn School of Pathology, The University of Oxford, South Parks Road, Oxford, UK.

出版信息

Vaccine. 2010 Mar 16;28(13):2482-9. doi: 10.1016/j.vaccine.2010.01.046. Epub 2010 Feb 2.

DOI:10.1016/j.vaccine.2010.01.046
PMID:20132920
Abstract

Carbopol is a polyanionic carbomer gel used in man for a variety of topical applications and drug delivery purposes. Here we show that subcutaneous administration of carbopol with glycoprotein antigens elicits unusually strong specific adaptive immune responses in mice. Recombinant soluble HIV-1 envelope glycoprotein (Env)-based antigen formulated in carbopol was at least as potent at stimulating Env-specific B and T cell responses as Freund's Complete Adjuvant, and significantly more potent than aluminium salts. The antigen-specific T cell immune response elicited both Th1 and Th2 cytokines including high titers of IFN-gamma, IL-2 and IL-4, and drove a Th1 isotype-switched antibody response. Mice immunized with a low dose of purified influenza HA in carbopol generated high titers of anti-HA antibodies and were protected from lethal challenge and disease with live virus. Similarly, immunization of mice with the melanoma cell line B16F10 formulated in carbopol significantly delayed tumor growth. We propose that carbopol, or related cross-linked polyacrylic acid analogues, may have promise for use as systemic vaccine adjuvants in man.

摘要

卡波姆是一种多阴离子的卡波姆凝胶,已在临床上用于多种局部应用和药物传递目的。在这里,我们发现卡波姆佐剂与糖蛋白抗原联合应用可在小鼠中引发异常强烈的特定适应性免疫反应。以卡波姆为佐剂配制的重组可溶性 HIV-1 包膜糖蛋白(Env)基于抗原刺激 Env 特异性 B 和 T 细胞反应的效力至少与弗氏完全佐剂相当,且明显强于铝盐佐剂。所引发的抗原特异性 T 细胞免疫反应既包括 Th1 细胞因子又包括 Th2 细胞因子,包括高滴度的 IFN-γ、IL-2 和 IL-4,并驱动 Th1 同型转换抗体反应。在卡波姆中用低剂量纯化的流感血凝素(HA)免疫的小鼠产生了高滴度的抗-HA 抗体,并可预防致死性攻击和活病毒引起的疾病。同样,用卡波姆配制的黑色素瘤细胞系 B16F10 免疫小鼠可显著延迟肿瘤生长。我们提出,卡波姆或相关交联聚丙烯酸类似物可能有望作为全身性疫苗佐剂在人类中应用。

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