Alkyl-esters of polyacrylic acid as vaccine adjuvants
Alkyl-esters of polyacrylic acid as vaccine adjuvants
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DOI：
10.1016/s0264-410x(98)00047-4
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发表时间：
1998-10-01
期刊：
影响因子：
5.5
通讯作者：
Boon, B
中科院分区：
文献类型：
--
作者：
Hilgers, LAT;Nicolas, I;Boon, B
以前，我们证明了聚丙烯酸（PAA）显着增强鸡对灭活纽卡斯尔病病毒（iNDV）的免疫应答，但效力不足以取代矿物油包水（W/O）佐剂用于加强致敏动物。为了提高PAA的佐剂性，采用辛醇和丁醇对PAA的羧基进行酯化，使重均分子量（M-w）为450 kDa的PAA接枝烷基链。得到的丁基-PAA和辛基-PRA酯的酯化度在10%和92%之间变化。在先前用iNDV致敏而没有佐剂的鸡中检查水溶性酯对iNDV的体液应答的佐剂活性。的烷基-PAA酯表现出显着更高的反应比未改性的PAA和滴度增加的佐剂剂量。在每只动物2 mg的剂量下，取代率为16%的辛基-和丁基-PAA酯（分别为辛基16-PAA和丁基16-PAA）的滴度与W/O相似。在早期用活NDV致敏的老年动物中，丁基16-PAA和W/O引起相当的抗体应答。丁基16-PAA在刺激小鼠的初级免疫应答方面也比PAA更有效，这伴随着通过监测注射部位的肿胀确定的更强的局部反应。丁基16-PAA的反应原性小于W/O。我们的结论是，烷基-PAA酯是一级和二级反应的强佐剂，它们是目前用于各种兽用疫苗的矿物油基佐剂的有前途的替代品。(C)1998爱思唯尔科技有限公司版权所有。
Previously, we demonstrated that polyacrylic acid (PAA) augmented significantly the immune response to inactivated Newcastle disease virus (iNDV) in chickens, but that efficacy was insufficient to replace the water-in-mineral oil (W/O) adjuvant applied for boosting primed animals. Attempting to improve its adjuvanticity, PAA with weight-average molecular weight (M-w) of 450 kDa was grafted with alkyl-chains by esterifying the carboxylic groups with octanol and butanol. The butyl-PAA and octyl-PRA esters obtained varied in degree of esterification between 10% and 92%. Adjuvant activity of water-soluble esters for humoral responses to iNDV was examined in chickens primed previously with iNDV without adjuvant. The alkyl-PAA esters exhibited significantly higher responses than unmodified PAA and titres increased with increasing dose of adjuvant. At doses of 2 mg per animal, octyl- and butyl-PAA esters with a substitution rate of 16% (octyl16-PAA and butyl16-PAA, respectively) gave similar titres as W/O. In aged animals primed with live NDV at early age, butyl16-PAA and W/O elicited comparable antibody responses. Butyl16-PAA was also more effective than PAA in stimulating primary immune responses in mice which was accompanied by stronger local reaction determined by monitoring swelling at the site of injection. Reactogenicity of butyl16-PAA was less than of W/O. We concluded that alkyl-PAA esters are strong adjuvants for primary and secondary responses and that they are promising alternatives to the mineral oil-based adjuvants presently used in various veterinary vaccines. (C) 1998 Elsevier Science Ltd. All rights reserved.