Sen L, Ghosh K, Bin Z, Qiang S, Thompson M G, Hawdon J M, Koski R A, Shuhua X, Hotez P J
Departments of Epidemiology and Public Health and Pediatrics, Yale University School of Medicine, New Haven, CT 06520, USA.
Vaccine. 2000 Jan 6;18(11-12):1096-102. doi: 10.1016/s0264-410x(99)00371-0.
Vaccination of mice with alum-precipitated recombinant Ancylostoma secreted protein-1 from the canine hookworm Ancylostoma caninum (Ac-ASP-1) results in protection against A. caninum larval challenge. Vaccine protection is manifested by host reductions in hookworm burden compared to control mice. The goal of this study was to determine whether ASP antigens cloned and expressed from different hookworm species will cross protect against A. caninum larval challenge. Cross-species protection against A. caninum challenge infections was observed with immunizations using recombinant ASP-1 from the human hookworms Ancylostoma duodenale and Necator americanus. However, the degree of protection was proportional to the extent of amino acid sequence homology between the ASP immunogen used for vaccination and the Ac-ASP-1 produced by the challenge larval strain. Vaccine protection was noted to decrease significantly as amino acid sequence homologies diverged 10% or more. It was also determined that Ac-ASP-2, a molecule cloned from A. caninum having 55% amino acid sequence homology to the C-terminus of Ac-ASP-1, did not elicit vaccine protection. These observations were partly reflected in the titer of antibodies that recognize Ac-ASP-1. The studies reported here will help to design immunogenic peptide vaccines based on the sequence divergence of hookworm ASPs.
用明矾沉淀的犬钩虫(犬弓首线虫)重组犬弓首线虫分泌蛋白-1(Ac-ASP-1)对小鼠进行疫苗接种,可使其免受犬弓首线虫幼虫攻击。与对照小鼠相比,疫苗保护表现为宿主体内钩虫负担减轻。本研究的目的是确定从不同钩虫物种克隆和表达的ASP抗原是否能交叉保护小鼠免受犬弓首线虫幼虫攻击。使用来自人钩虫十二指肠钩口线虫和美洲板口线虫的重组ASP-1进行免疫接种时,观察到了对犬弓首线虫攻击感染的跨物种保护。然而,保护程度与用于疫苗接种的ASP免疫原和攻击幼虫株产生的Ac-ASP-1之间的氨基酸序列同源程度成正比。当氨基酸序列同源性差异达到10%或更多时,疫苗保护作用显著降低。还确定了从犬弓首线虫克隆的Ac-ASP-2,其与Ac-ASP-1的C末端具有55%的氨基酸序列同源性,但并未引发疫苗保护作用。这些观察结果部分反映在识别Ac-ASP-1的抗体滴度上。本文报道的研究将有助于基于钩虫ASP的序列差异设计免疫原性肽疫苗。