A Schistosoma mansoni fatty acid-binding protein, Sm14, is the potential basis of a dual-purpose anti-helminth vaccine.

Abstract

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 (8-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, rSml4, 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. Schistosomiasis, caused principally by Schistosoma mansoni, S. haematobium, and S. japonicum, afflicts some 200 million individuals in tropical regions of the world. Fascioliasis caused by Fasciola hepatica is an economically important disease of cattle and sheep in Europe, the Americas, Australia, and New Zealand. There are no vaccines against Schistosoma or Fasciola species; however, there is evidence for protective immune crossreactivity between S. mansoni and F. hepatica. Hillyer and coworkers (1-3) have isolated a low molecular weight F. hepatica fraction that protects against both S. mansoni and F. hepatica infections. A component of this fraction is an antigen with homology to mammalian fatty acid-binding proteins that is termed Fhl5 (4). A similar antigen, Sm14, was cloned from S. mansoni following studies of a protective saline extract of adult worms, SE (5). These results suggested that the pair of similar parasite proteins could mediate immune crossreaction and represent the basis of a subunit vaccine effective against both species. We have investigated the molecular relationship of Fhl5, Sml4, and mammalian fatty acid-binding proteins (FABPs) (6) (9), and rat intestine (10) were obtained directly from the Brookhaven Protein Data Bank (accession codes 2HMB, 1ALB, and 2IFB, respectively). Sequences of known crystal structure were aligned by leastsquares superposition of the molecules using C' coordinates alone, and the remaining sequences were subsequently incorporated into the alignment by the method of Barton and Sternberg (11) as implemented in the AMPS package.For the construction of the Sm14 model, the backbone of the 10 (3-strands and three a-helices was based on that of 1ALB. (3-Turn types were determined on the basis of the position of glycine and/or asparagine and aspartic residues within ...

Schistosomes—proteomics studies for potential novel vaccines and drug targets

“…Several candidates have been proposed in the 1980s and 1990s. Their discovery was based mainly on the recognition of these proteins by protective antibodies/serum or high immunogenicity [14][15][16][17][18][19]. Despite promising preliminary results, tests with six selected antigens (glutathione-S-transferase (SmGST), triose phosphate isomerase (TPI), paramyosin, 23 kDa integral membrane tetraspanin protein (Sm23), myosin heavy chain (IrV5) and 14 kDa fatty acid binding protein (Sm14)) by independently contracted laboratories in the Schistosoma mansoni/ mouse experimental system showed disappointing results [20].…”

Protective immunity of single and multi-antigen DNA vaccines against schistosomiasis

“…Preparation of DNA vaccines -Three DNA vaccine constructions were used: pECL codes for the 200 kDa glycosylphosphatidylinositol-anchored surface protein involved on the immune response to praziquantel treatment (Sauma et al 1991); pSm14 codes another tegumental protein involved on the transport of fatty acids (Tendler et al 1996); and pIrV5 (Soisson et al 1992 codes for a 62 kDa muscle protein. All constructions were obtained from an overnight batch fermentation of the plasmid recombinant harboring Escherichia coli DH5α strains.…”

Sm14 gene expression in different stages of the Schistosoma mansoni life cycle and immunolocalization of the Sm14 protein within the adult worm

“…Recently, the World Health Organization selected six molecule candidates to compose a subunit vaccine against schistosomiasis (3). One of them is Sm14, a 14-kDa Schistosoma mansoni antigen that induces partial protection in mice following vaccination and cercarial challenge (4). Sm14 is a cytoplasmic fatty acid-binding protein (FABP) and its ability to bind to palmitic and linolenic acids in vitro has been demonstrated (5).…”