Silva Everton F, Medeiros Marco A, McBride Alan J A, Matsunaga Jim, Esteves Gabriela S, Ramos João G R, Santos Cleiton S, Croda Júlio, Homma Akira, Dellagostin Odir A, Haake David A, Reis Mitermayer G, Ko Albert I
Gonçalo Moniz Research Centre, Oswaldo Cruz Foundation, Brazilian Ministry of Health, Salvador, Brazil.
Vaccine. 2007 Aug 14;25(33):6277-86. doi: 10.1016/j.vaccine.2007.05.053. Epub 2007 Jun 14.
Subunit vaccines are a potential intervention strategy against leptospirosis, which is a major public health problem in developing countries and a veterinary disease in livestock and companion animals worldwide. Leptospiral immunoglobulin-like (Lig) proteins are a family of surface-exposed determinants that have Ig-like repeat domains found in virulence factors such as intimin and invasin. We expressed fragments of the repeat domain regions of LigA and LigB from Leptospira interrogans serovar Copenhageni. Immunization of Golden Syrian hamsters with Lig fragments in Freund's adjuvant induced robust antibody responses against recombinant protein and native protein, as detected by ELISA and immunoblot, respectively. A single fragment, LigANI, which corresponds to the six carboxy-terminal Ig-like repeat domains of the LigA molecule, conferred immunoprotection against mortality (67-100%, P<0.05) in hamsters which received a lethal inoculum of L. interrogans serovar Copenhageni. However, immunization with this fragment did not confer sterilizing immunity. These findings indicate that the carboxy-terminal portion of LigA is an immunoprotective domain and may serve as a vaccine candidate for human and veterinary leptospirosis.
亚单位疫苗是一种针对钩端螺旋体病的潜在干预策略,钩端螺旋体病在发展中国家是一个主要的公共卫生问题,在全球范围内的家畜和伴侣动物中是一种兽医疾病。钩端螺旋体免疫球蛋白样(Lig)蛋白是一类表面暴露的决定簇,其具有在诸如紧密黏附素和侵袭素等毒力因子中发现的Ig样重复结构域。我们表达了问号钩端螺旋体哥本哈根血清型的LigA和LigB重复结构域区域的片段。用弗氏佐剂中的Lig片段免疫金黄叙利亚仓鼠,分别通过ELISA和免疫印迹检测到,诱导了针对重组蛋白和天然蛋白的强烈抗体反应。一个单一的片段LigANI,它对应于LigA分子的六个羧基末端Ig样重复结构域,在接受问号钩端螺旋体哥本哈根血清型致死接种物的仓鼠中,赋予了针对死亡率的免疫保护(67 - 100%,P<0.05)。然而,用该片段免疫并未赋予无菌免疫力。这些发现表明,LigA的羧基末端部分是一个免疫保护结构域,可能作为人类和兽医钩端螺旋体病的候选疫苗。