Potentiation of the immune response to non-adsorbed antigens by aluminum-containing adjuvants

Potentiation of the immune response to non-adsorbed antigens by aluminum-containing adjuvants
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DOI:
10.1016/j.vaccine.2006.09.039
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发表时间:
2007-01-15
期刊:
影响因子:
5.5
通讯作者:
Hem, Stanley L.
Hem, Stanley L.
中科院分区:
医学3区
文献类型:
--
作者:
Mendez, Ilia Z. Romero;Shi, Yi;Hem, Stanley L.

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含铝佐剂对抗原的吸附程度被认为是疫苗的一个重要特征,它与佐剂的免疫增强有关。本研究检测了磷酸铝佐剂在三种模型疫苗中的免疫增强作用,其中抗原不吸附在疫苗制剂中,也不与体外组织液混合。在第一种模型疫苗中,磷酸铝佐剂用0.5 M KH2PO4预处理,以尽量减少对去磷酸化α酪蛋白的吸附。第二种模型疫苗由磷酸铝佐剂和经马铃薯酸性磷酸酶处理去磷酸化的卵清蛋白组成。第三种模型疫苗由磷酸铝佐剂和溶菌酶(LYS)组成。为了防止溶菌酶的吸附,用纤维蛋白原预处理磷酸铝佐剂,纤维蛋白原是存在于组织液中的一种与磷酸铝佐剂结合强烈的蛋白质。通过测定小鼠的抗体产生来评价免疫增强作用。结果发现,三种模型疫苗诱导的抗体滴度均高于无佐剂抗原溶液诱导的抗体滴度,且与磷酸铝佐剂吸附抗原的疫苗相似。共聚焦显微镜实验表明,这些实验中使用的抗原。即使没有吸附到磷酸铝佐剂上,也被困在佐剂聚集体内的空隙中,导致树突状细胞对抗原的不良摄取。(c) 2006 Elsevier Ltd.版权所有。
The degree of antigen adsorption by aluminium-containing adjuvants is considered an important characteristic of vaccines that is related to immunopotentiation by the adjuvant. This study examined immunopotentiation by aluminum phosphate adjuvant in three model vaccines in which the antigen was not adsorbed in the vaccine formulation nor when mixed in vitro with interstitial fluid. In the first model vaccine, aluminum phosphate adjuvant was pre-treated with 0.5 M KH2PO4 to minimize the adsorption of dephosphorylated alpha casein. The second model vaccine was composed of aluminum phosphate adjuvant and ovalbumin that was dephosphorylated by treatment with potato acid phosphatase. The third model vaccine consisted of all,aluminium phosphate adjuvant and lysozyme (LYS). In order to prevent adsorption of lysozyme, the aluminum phosphate adjuvant was pre-treated with fibrinogen, a protein present in interstitial fluid that binds strongly to aluminum phosphate adjuvant. Immunopotentiation was evaluated by measuring antibody production in mice. It was found that all three model vaccines induced antibody titers that were statistically higher than induced by,I solution of antigen without adjuvant and similar to vaccines in which the antigens were adsorbed by aluminium phosphate adjuvant. Confocal microscopy experiments suggested that the antigens used in these experiments. even though not adsorbed to the aluminum phosphate adjuvant, were trapped in void spaces within the adjuvant aggregates, resulting ill uptake of antigen by dendritic cells. (c) 2006 Elsevier Ltd. All rights reserved.