Tendler M, Brito C A, Vilar M M, Serra-Freire N, Diogo C M, Almeida M S, Delbem A C, Da Silva J F, Savino W, Garratt R C, Katz N, Simpson A S
Instituto Oswaldo Cruz-Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
Proc Natl Acad Sci U S A. 1996 Jan 9;93(1):269-73. doi: 10.1073/pnas.93.1.269.
Molecular cloning of components of protective antigenic preparations has suggested that related parasite fatty acid-binding proteins could form the basis of the protective immune crossreactivity between the parasitic trematode worms Fasciola hepatica and Schistosoma mansoni. Molecular models of the two parasite proteins showed that both molecules adopt the same basic three-dimensional structure, consisting of a barrel-shaped molecule formed by 10 antiparallel beta-pleated strands joined by short loops, and revealed the likely presence of crossreactive, discontinuous epitopes principally derived from amino acids in the C-terminal portions of the molecules. A recombinant form of the S. mansoni antigen, rSm14, protected outbred Swiss mice by up to 67% against challenge with S. mansoni cercariae in the absence of adjuvant and without provoking any observable autoimmune response. The same antigen also provided complete protection against challenge with F. hepatica metacercariae in the same animal model. The results suggest that it may be possible to produce a single vaccine that would be effective against at least two parasites, F. hepatica and S. mansoni, of veterinary and human importance, respectively.
保护性抗原制剂成分的分子克隆表明，相关的寄生虫脂肪酸结合蛋白可能构成寄生吸虫肝片吸虫和曼氏血吸虫之间保护性免疫交叉反应的基础。两种寄生虫蛋白的分子模型显示，这两种分子都具有相同的基本三维结构，由一个桶状分子组成，该分子由10条反平行的β折叠链通过短环连接而成，并揭示了可能存在的交叉反应性、不连续表位，主要源自分子C末端部分的氨基酸。曼氏血吸虫抗原的重组形式rSm14，在无佐剂且未引发任何可观察到的自身免疫反应的情况下，使远交系瑞士小鼠对曼氏血吸虫尾蚴攻击的保护率高达67%。在同一动物模型中，相同的抗原也对肝片吸虫囊蚴攻击提供了完全保护。结果表明，有可能生产出一种单一疫苗，分别对具有兽医和人类重要性的至少两种寄生虫——肝片吸虫和曼氏血吸虫有效。
