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不同佐剂对3型副流感病毒原型亚单位疫苗免疫原性的免疫刺激特性比较分析

Comparative analysis of the immunostimulatory properties of different adjuvants on the immunogenicity of a prototype parainfluenza virus type 3 subunit vaccine.

作者信息

Ewasyshyn M, Caplan B, Bonneau A M, Scollard N, Graham S, Usman S, Klein M

机构信息

Connaught Centre for Biotechnology Research, Willowdale, Ontario, Canada.

出版信息

Vaccine. 1992;10(6):412-20. doi: 10.1016/0264-410x(92)90072-r.

DOI:10.1016/0264-410x(92)90072-r
PMID:1317984
Abstract

The immunogenicity of a parainfluenza virus type 3 (PIV-3) subunit vaccine consisting of affinity-purified haemagglutinin-neuraminidase (HN) and fusion (F) surface glycoproteins was tested in guinea-pigs and hamsters. The ability of several different immunopotentiating agents to enhance the antibody response of animals to the PIV-3 surface glycoproteins was evaluated. The immunity induced by HN and F alone was compared with the response elicited by purified proteins combined with Freund's complete adjuvant, aluminium phosphate, Syntex's threonyl-muramyl dipeptide (MDP) SAF-MF formulation, or Ribi's adjuvant formulation containing BCG cell wall skeleton (CWS), trehalose dimycolate (TDM) and monophosphoryl lipid A (MPL) in a 2% squalene-in-water emulsion. Purified proteins were also incorporated into three different liposome formulations prepared by the detergent dialysis procedure. Immunization of guinea-pigs and hamsters with two 15 micrograms doses of the PIV-3 surface glycoproteins administered in the absence of adjuvant elicited high haemagglutination inhibition, neutralization and anti-fusion titres. The liposome preparations failed to enhance the antibody titres. Ribi's adjuvant formulation was effective at inducing a good secondary response to the purified proteins while the immunostimulatory effects of aluminium phosphate, Syntex and Freund's adjuvants were clearly demonstrated in both primary and secondary responses. When administered without adjuvant, a 15 microgram dose of the HN and F mixture was capable of protecting hamsters against live virus challenge. The immunoprotective dose of the purified proteins could be reduced to at least 0.1 microgram by the addition of aluminium phosphate, Syntex or Freund's adjuvants.

摘要

对由亲和纯化的血凝素神经氨酸酶(HN)和融合(F)表面糖蛋白组成的3型副流感病毒(PIV - 3)亚单位疫苗的免疫原性在豚鼠和仓鼠中进行了测试。评估了几种不同免疫增强剂增强动物对PIV - 3表面糖蛋白抗体反应的能力。将单独的HN和F诱导的免疫力与纯化蛋白与弗氏完全佐剂、磷酸铝、先灵葆雅的苏氨酰 - 胞壁酰二肽(MDP)SAF - MF制剂或里比佐剂制剂(含有卡介苗细胞壁骨架(CWS)、海藻糖二霉菌酸酯(TDM)和单磷酰脂质A(MPL),在2%水包角鲨烷乳剂中)联合引发的反应进行了比较。纯化蛋白还被掺入通过去污剂透析程序制备的三种不同脂质体制剂中。在无佐剂情况下用两剂15微克的PIV - 3表面糖蛋白免疫豚鼠和仓鼠,引发了高血凝抑制、中和及抗融合效价。脂质体制剂未能提高抗体效价。里比佐剂制剂在诱导对纯化蛋白的良好二次反应方面有效,而磷酸铝、先灵葆雅和弗氏佐剂的免疫刺激作用在初次和二次反应中均得到明确证明。在无佐剂情况下给药时,15微克剂量的HN和F混合物能够保护仓鼠免受活病毒攻击。通过添加磷酸铝、先灵葆雅或弗氏佐剂,纯化蛋白的免疫保护剂量可降低至至少0.1微克。

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