Schistosomiasis Vaccine:Research to Development

Bergquist, N.R.; Colley, Daniel G.

doi:10.1016/s0169-4758(97)01207-6

Cited by 209 publications

(111 citation statements)

References 14 publications

Supporting

Mentioning

101

Contrasting

Unclassified

Order By: Relevance

“…Selection based on protective monoclonal antibodies such as glutathione-Stransferase (GST) [10] and triosephosphate isomerase (TPI) [11], by unique antigen recognition by strong natural resistance in humans [12] or animals [13], or by antigen selection using the radiation-attenuated cercariae vaccine (RAC) model [14─16]. For example, a fragment of myosin of S. mansoni (SmIrV-5); one of the vaccine candidate antigens selected by TDR/WHO committee [17], was identified using serum from mice exposed to RAC [18]. None of the antigens identified conferred equivalent efficacy of the vaccination using RAC [5,19,20].…”

Section: Introductionmentioning

confidence: 99%

Proteome approach for identification of schistosomiasis japonica vaccine candidate antigen

Abdel-Hafeez

Kikuchi

Watanabe

et al. 2009

Parasitology International

View full text Add to dashboard Cite

Experimental vaccination with radiation-attenuated cercariae (RAC) confers possible practical levels of resistance to challenge infection by humoral and by cellular mechanism. Here, we aimed to identify possible vaccine antigens by using specific IgG antibody from RAC vaccinated miniature pig. Two milligrams of soluble egg antigen (SEA) or schistosomal worm antigen preparation (SWAP) was fractionated using two dimensional liquid chromatography From the positive fractions we chose 17 of SEA and 10 of SWAP that had no reactivity with normal cercariae infected (NCI) sera and had single peak of 214 nm; and automated N-terminal amino acid sequence based on in situ Edman Reaction was conducted. Four sequences were obtained and applied to the homology search in NCBI database. A total of eight candidate genes were listed up and their cDNA clones from schistosomula stage were obtained. Two of the recombinant proteins (AAW27472.1 and AXX25883.1) showed strong reactivity with the RAC vaccinated serum but marginal with NCI serum. This protocol using proteome PF2D could be applicable in identifying immunoreactive proteins from crude extract for the development of vaccines or for diagnostics.

show abstract

Section: Introductionmentioning

confidence: 99%

Proteome approach for identification of schistosomiasis japonica vaccine candidate antigen

Abdel-Hafeez

Kikuchi

Watanabe

et al. 2009

Parasitology International

View full text Add to dashboard Cite

show abstract

“…We concentrate here on the anatomic and parasitologic features of various models and on the use of models to address mechanisms of pathogenesis. Reviews dealing with immunopathology (Lukacs & Boros 1993, Fallon 2000 and with immunization and resistance to reinfection (James 1995, Richter et al 1995, Coulson 1997, Waine & McManus 1997, Bergquist & Colley 1998) have been recently published.…”

mentioning

confidence: 99%

Experimental models of Schistosoma mansoni infection

Cheever

Lenzi²,

Lenzi³

et al. 2002

Mem. Inst. Oswaldo Cruz

123

View full text Add to dashboard Cite

“…Despite significant efforts, the molecular basis of drug recognition by human cytochrome P450 proteins has remained elusive. Here we describe crystal structures of human cytochrome P450 proteins, CYP2C9 [1] and CYP3A4 both in an unliganded form and in complex with marketed drugs. CYP3A4 is the most important member of P450 family, responsible for metabolising 50 % of drugs while CYP2C9 metabolises some 15 % of all marketed therapeutics.…”

mentioning

confidence: 99%

Crystal structure of Y10F mutant of Sh28GST: insight into GSH activation mechanism and isomerisation of prostaglandin H2 to prostaglandin D2

Miele¹,

Angelucci²,

Baiocco³

et al. 2004

Acta Cryst Sect A

View full text Add to dashboard Cite

The mammalian cytochrome P450 enzymes are a family of membrane-associated haem-containing proteins which play a major role in the metabolism of numerous and diverse xenobiotics such as drug molecules. Despite significant efforts, the molecular basis of drug recognition by human cytochrome P450 proteins has remained elusive. Here we describe crystal structures of human cytochrome P450 proteins, CYP2C9 [1] and CYP3A4 both in an unliganded form and in complex with marketed drugs. CYP3A4 is the most important member of P450 family, responsible for metabolising 50 % of drugs while CYP2C9 metabolises some 15 % of all marketed therapeutics. These crystal structures provide insights into the principles of substrate binding for these promiscuous enzymes.[ Parasitic diseases are a major threat on human health and Schistsomiasis is second only to malaria for the number of people affected and the gravity of pathology, although it is spread only in tropical and sub-tropical areas. A collaboration between the University of Rome "La Sapienza" and the Pasteur Institute at Lille has led to the 1.8Å X-ray crystal structure of the Schistosoma haematobium 28kD glutathione S-transferase (Sh28GST), which is a major antigen and a putative vaccine in fase 2 clinical trials [1]. Sh28GST is thought to protect the schistosome from xenobiotic attack via a detoxification process or simply by binding and sequestering toxic compounds. Sh28GST has also been demonstrated to have a high prostaglandin D 2 synthase activity. Prostaglandin D2 is able to control the human cutaneous immune response helping schistosomes to escape the host immune system [2]. The overall fold of Sh28GST is similar to that of all other GST's: GSH binds to the N-terminal thioredoxin-like domain, while substrates for GST transferase activity bind to the C-terminal alpha-helical domain. Despite extensive dialysis prior to crystallization, the active site is still 40% saturated with GSH in the crystal and shows a unique feature which has not been reported in other GST structures: the crucial active site Tyr10 side chain occupies two different positions [3]. One of those two positions is a non-canonical rotamer: the phenolic ring is found away from the active site, tilted towards the exterior of the protein, with the OH exposed to the solvent. This unusual conformer is stabilized by an on-face H-bond with the conserved Arg21. The question arose whether this new conformer was an artifact due to crystallographic contacts; hence we produced, expressed, purified, crystallized and solved the structure of the Y10F mutant of Sh28GST at 1.9.Å. The structure is superimposable to the wild type and presents the same characteristics also with respect to the residue in position 10. The on-face hydrogen bond is still maintained between the Arg21 and the benzene ring of the Phe10, confirming what it has been previously observed. Moreover the Y10F mutant is not functional either in activating glutathione or to the isomerization of prostaglandins. These results could be rationalized with our ...

show abstract

Schistosomiasis Vaccine:Research to Development

Cited by 209 publications

References 14 publications

Proteome approach for identification of schistosomiasis japonica vaccine candidate antigen

Proteome approach for identification of schistosomiasis japonica vaccine candidate antigen

Experimental models of Schistosoma mansoni infection

Crystal structure of Y10F mutant of Sh28GST: insight into GSH activation mechanism and isomerisation of prostaglandin H2 to prostaglandin D2

Contact Info

Product

Resources

About