Turbyfill K Ross, Kaminski Robert W, Oaks Edwin V
Division of Bacterial and Rickettsial Diseases, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910-7500, USA.
Vaccine. 2008 Mar 4;26(10):1353-64. doi: 10.1016/j.vaccine.2007.12.040. Epub 2008 Jan 17.
Development of a subunit vaccine for shigellosis requires identification of protective antigens and delivering these antigens in a manner that stimulates immunity comparable to that induced by natural infection. The Shigella invasin complex (Invaplex) vaccine is an ion-exchange-purified extract from virulent Shigella that consists of LPS and several other proteins, including the invasins IpaB and IpaC. Intranasal delivery of Invaplex stimulates protective immunity in small animal models for shigellosis. To identify the active component(s) of Invaplex responsible for its immunogenicity and efficacy, size-exclusion chromatography (SEC) was used to separate Invaplex into several different fractions. A high-molecular mass complex with a molecular mass between 669 MDa and 2 MDa consisted primarily of LPS, IpaB and IpaC and was considered to be a highly purified (HP) form of Invaplex. Using the mouse lung model to evaluate the immunogenicity and efficacy of the SEC fractions it was clearly demonstrated that the high-molecular mass complex of the invasins and LPS was responsible for the protective capacity of parent native Invaplex. Other smaller mass SEC fractions were mostly non-immunogenic and did not stimulate solid protection. In guinea pigs, the HP Invaplex stimulated an enhanced immune response as compared to the parent Invaplex and was fully protective. Isolation and characterization of the immunogenic and protective moiety within Invaplex will allow better standardization of the Invaplex product and may allow future development of an Invaplex assembled from purified components.
开发用于志贺氏菌病的亚单位疫苗需要鉴定保护性抗原，并以能刺激产生与自然感染所诱导的免疫力相当的方式递送这些抗原。志贺氏菌侵袭素复合物（Invaplex）疫苗是一种从有毒力的志贺氏菌中通过离子交换纯化得到的提取物，它由脂多糖（LPS）和其他几种蛋白质组成，包括侵袭素IpaB和IpaC。经鼻内递送Invaplex可在志贺氏菌病的小动物模型中刺激产生保护性免疫。为了鉴定Invaplex中负责其免疫原性和功效的活性成分，采用尺寸排阻色谱法（SEC）将Invaplex分离成几个不同的组分。一种分子量在669 MDa至2 MDa之间的高分子量复合物主要由LPS、IpaB和IpaC组成，被认为是Invaplex的一种高度纯化（HP）形式。利用小鼠肺部模型评估SEC组分的免疫原性和功效，结果清楚地表明，侵袭素和LPS的高分子量复合物是母体天然Invaplex具有保护能力的原因。其他分子量较小的SEC组分大多无免疫原性，不能刺激产生可靠的保护作用。在豚鼠中，与母体Invaplex相比，HP Invaplex刺激产生了更强的免疫反应，并且具有完全的保护作用。对Invaplex中免疫原性和保护性部分进行分离和表征，将有助于更好地对Invaplex产品进行标准化，并可能有助于未来开发由纯化成分组装而成的Invaplex。
