Vernazza Claire, Lingard Bry, Flick-Smith Helen C, Baillie Leslie W J, Hill Jim, Atkins Helen S
Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire, SP4 0JQ, UK.
Vaccine. 2009 May 11;27(21):2775-80. doi: 10.1016/j.vaccine.2009.03.011. Epub 2009 Mar 13.
Yersinia pestis is the causative agent of plague. Naturally occurring cases of the disease and the potential use of Y. pestis as a bioweapon fuel the need for efficacious vaccines. The most recent plague vaccine is a killed whole cell preparation that is expensive to manufacture and its side effects are common. The protective antigens F1 and V have been identified and are currently being developed as a combined subunit vaccine. Protective epitopes of the V antigen have previously been shown to reside in the central part of the protein. In order to identify the minimum protective fragment of the V antigen that can provide protection against plague, the structures of several small fragments of the antigen were modelled in silico and recombinant proteins were produced. These fragments were probed for the retention of a protective epitope using a protective monoclonal antibody and protection against Y. pestis in mice was determined. The smallest protective fragment of V antigen identified comprised amino acids 135-262. Finally the ability of this fragment to confer protection when given in the context of a DNA vaccine was confirmed.
鼠疫耶尔森菌是鼠疫的病原体。该疾病的自然发生病例以及鼠疫耶尔森菌作为生物武器的潜在用途促使人们需要有效的疫苗。最新的鼠疫疫苗是一种灭活全细胞制剂，生产成本高昂且副作用常见。保护性抗原F1和V已被鉴定出来，目前正在开发一种联合亚单位疫苗。V抗原的保护性表位先前已被证明位于该蛋白质的中央部分。为了鉴定V抗原能够提供鼠疫防护的最小保护片段，在计算机上模拟了该抗原几个小片段的结构并制备了重组蛋白。使用一种保护性单克隆抗体检测这些片段是否保留保护性表位，并测定其对小鼠鼠疫耶尔森菌的防护作用。鉴定出的V抗原最小保护片段包含氨基酸135 - 262。最后证实了该片段在DNA疫苗背景下给予时赋予保护的能力。
