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纤连蛋白的外域 A(EDA)与聚肌苷酸结合可增强对 HIV-1 p24 蛋白的免疫应答,并在小鼠模型中对重组李斯特菌-Gag 感染起到保护作用。

The extradomain A of fibronectin (EDA) combined with poly(I:C) enhances the immune response to HIV-1 p24 protein and the protection against recombinant Listeria monocytogenes-Gag infection in the mouse model.

机构信息

Instituto de Agrobiotecnología (CSIC-UPNA-Gobierno de Navarra), Carretera de Mutilva, sn. 31192 Mutilva, Navarra, Spain.

出版信息

Vaccine. 2012 Mar 28;30(15):2564-9. doi: 10.1016/j.vaccine.2012.01.081. Epub 2012 Feb 8.

Abstract

The development of effective vaccines against HIV-1 infection constitutes one of the major challenges in viral immunology. One of the protein candidates in vaccination against this virus is p24, since it is a conserved HIV antigen that has cytotoxic and helper T cell epitopes as well as B cell epitopes that may jointly confer enhanced protection against infection when used in immunization-challenge approaches. In this context, the adjuvant effect of EDA (used as EDAp24 fusion protein) and poly(I:C), as agonists of TLR4 and TLR3, respectively, was assessed in p24 immunizations using a recombinant Listeria monocytogenes HIV-1 Gag proteins (Lm-Gag, where p24 is the major antigen) for challenge in mice. Immunization with EDAp24 fusion protein together with poly(I:C) adjuvant induced a specific p24 IFN-γ production (Th1 profile) as well as protection against a Lm-Gag challenge, suggesting an additive or synergistic effect between both adjuvants. The combination of EDA (as a fusion protein with the antigen, which may favor antigen targeting to dendritic cells through TLR4) and poly(I:C) could thus be a good adjuvant candidate to enhance the immune response against HIV-1 proteins and its use may open new ways in vaccine investigations on this virus.

摘要

针对 HIV-1 感染的有效疫苗的开发是病毒免疫学的主要挑战之一。该病毒疫苗接种的候选蛋白之一是 p24,因为它是一种保守的 HIV 抗原,具有细胞毒性和辅助 T 细胞表位,以及 B 细胞表位,当用于免疫接种-挑战方法时,这些表位可能共同赋予对感染的增强保护作用。在这种情况下,使用重组李斯特菌单核细胞增生李斯特菌 HIV-1 Gag 蛋白(Lm-Gag,其中 p24 是主要抗原)对小鼠进行挑战,评估了 EDA(用作 EDAp24 融合蛋白)和聚肌苷酸(poly(I:C))作为 TLR4 和 TLR3 的激动剂在 p24 免疫接种中的佐剂效应。与佐剂 poly(I:C)一起用 EDAp24 融合蛋白免疫诱导了特异性的 p24 IFN-γ 产生(Th1 谱)以及对 Lm-Gag 挑战的保护,表明两种佐剂之间存在相加或协同作用。因此,EDA(作为与抗原的融合蛋白,这可能通过 TLR4 有利于抗原靶向树突状细胞)和 poly(I:C)的组合可能是增强针对 HIV-1 蛋白的免疫反应的良好佐剂候选物,其使用可能为该病毒的疫苗研究开辟新途径。

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