Limits...
Inconsistent protective efficacy and marked polymorphism limits the value of Schistosoma japonicum tetraspanin-2 as a vaccine target.

Zhang W, Li J, Duke M, Jones MK, Kuang L, Zhang J, Blair D, Li Y, McManus DP - PLoS Negl Trop Dis (2011)

Bottom Line: We determined the protective efficacy of one subclass - Sj-TSP-2e.Following the alignment of 211 cDNAs, we identified 7 clusters encoding S. japonicum TSP-2 (Sj-TSP-2) based on sequence variation in the large extracellular loop (LEL) region with differing frequency of transcription in male and female worms.We expressed in E. coli the LEL region of one of the clusters which exhibited a high frequency of transcription in female worms, and showed the purified recombinant protein (Sj-TSP-2e) was recognised by 43.1% of sera obtained from confirmed schistosomiasis japonica patients.

View Article: PubMed Central - PubMed

Affiliation: Molecular Parasitology Laboratory, Australian Centre for International and Tropical Health and Nutrition, Queensland Institute of Medical Research, Brisbane, Queensland, Australia.

ABSTRACT

Background: Schistosoma mansoni tetraspanin 2 (Sm-TSP-2) has been shown to be strongly recognized by IgG1 and IgG3 antibodies from individuals putatively resistant to schistosome infection, but not chronically infected people, and to induce high levels of protection against challenge infection in the murine model of schistosomiasis. Amplification by PCR of homologous sequences from male and female S. japonicum worms showed the presence of 7 different clusters or subclasses of S. japonicum TSP-2. We determined the protective efficacy of one subclass - Sj-TSP-2e.

Methodology/principal findings: Following the alignment of 211 cDNAs, we identified 7 clusters encoding S. japonicum TSP-2 (Sj-TSP-2) based on sequence variation in the large extracellular loop (LEL) region with differing frequency of transcription in male and female worms. Quantitative PCR analysis revealed elevated expression of Sj-TSP-2 in adult worms compared with other life cycle stages. We expressed in E. coli the LEL region of one of the clusters which exhibited a high frequency of transcription in female worms, and showed the purified recombinant protein (Sj-TSP-2e) was recognised by 43.1% of sera obtained from confirmed schistosomiasis japonica patients. Vaccination of mice with the recombinant protein induced high levels of IgG1 and IgG2 antibodies, but no consistent protective efficacy against challenge infection was elicited in three independent trials.

Conclusions/significance: The highly polymorphic nature of the Sj-TSP-2 gene at the transcriptional level may limit the value of Sj-TSP-2 as a target for future S. japonicum vaccine development.

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Related in: MedlinePlus

Phylogenetic analysis of Sj-TSP-2 clusters with homologues.Protein sequences corresponding to the LEL region of Sj-TSP-2 encoded by 9 clusters of Sj-TSP-2 cDNAs were aligned with additional homologues found by BLAST searches in GenBank and others reported by Cai et al [8]. Analysis was done as stated in the text. Clade credibility (posterior probability) values are shown at nodes. Protein sequence data reported in this paper are available in the GenBank, EMBL and DDBJ databases under the accession numbers ABR27733, AAX26611 and CAX70617.
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pntd-0001166-g002: Phylogenetic analysis of Sj-TSP-2 clusters with homologues.Protein sequences corresponding to the LEL region of Sj-TSP-2 encoded by 9 clusters of Sj-TSP-2 cDNAs were aligned with additional homologues found by BLAST searches in GenBank and others reported by Cai et al [8]. Analysis was done as stated in the text. Clade credibility (posterior probability) values are shown at nodes. Protein sequence data reported in this paper are available in the GenBank, EMBL and DDBJ databases under the accession numbers ABR27733, AAX26611 and CAX70617.

Mentions: A phylogenetic tree of the Sj-TSP-2 sequences found using MrBayes is shown in Figure 2. Twelve different sequences for the LEL were found in S. japonicum. These differed from each other by between 1 and 22 sites. Pair-wise differences between any sequence from S. japonicum and the homologue from S. mansoni ranged from 28 to 33.


Inconsistent protective efficacy and marked polymorphism limits the value of Schistosoma japonicum tetraspanin-2 as a vaccine target.

Zhang W, Li J, Duke M, Jones MK, Kuang L, Zhang J, Blair D, Li Y, McManus DP - PLoS Negl Trop Dis (2011)

Phylogenetic analysis of Sj-TSP-2 clusters with homologues.Protein sequences corresponding to the LEL region of Sj-TSP-2 encoded by 9 clusters of Sj-TSP-2 cDNAs were aligned with additional homologues found by BLAST searches in GenBank and others reported by Cai et al [8]. Analysis was done as stated in the text. Clade credibility (posterior probability) values are shown at nodes. Protein sequence data reported in this paper are available in the GenBank, EMBL and DDBJ databases under the accession numbers ABR27733, AAX26611 and CAX70617.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3104969&req=5

pntd-0001166-g002: Phylogenetic analysis of Sj-TSP-2 clusters with homologues.Protein sequences corresponding to the LEL region of Sj-TSP-2 encoded by 9 clusters of Sj-TSP-2 cDNAs were aligned with additional homologues found by BLAST searches in GenBank and others reported by Cai et al [8]. Analysis was done as stated in the text. Clade credibility (posterior probability) values are shown at nodes. Protein sequence data reported in this paper are available in the GenBank, EMBL and DDBJ databases under the accession numbers ABR27733, AAX26611 and CAX70617.
Mentions: A phylogenetic tree of the Sj-TSP-2 sequences found using MrBayes is shown in Figure 2. Twelve different sequences for the LEL were found in S. japonicum. These differed from each other by between 1 and 22 sites. Pair-wise differences between any sequence from S. japonicum and the homologue from S. mansoni ranged from 28 to 33.

Bottom Line: We determined the protective efficacy of one subclass - Sj-TSP-2e.Following the alignment of 211 cDNAs, we identified 7 clusters encoding S. japonicum TSP-2 (Sj-TSP-2) based on sequence variation in the large extracellular loop (LEL) region with differing frequency of transcription in male and female worms.We expressed in E. coli the LEL region of one of the clusters which exhibited a high frequency of transcription in female worms, and showed the purified recombinant protein (Sj-TSP-2e) was recognised by 43.1% of sera obtained from confirmed schistosomiasis japonica patients.

View Article: PubMed Central - PubMed

Affiliation: Molecular Parasitology Laboratory, Australian Centre for International and Tropical Health and Nutrition, Queensland Institute of Medical Research, Brisbane, Queensland, Australia.

ABSTRACT

Background: Schistosoma mansoni tetraspanin 2 (Sm-TSP-2) has been shown to be strongly recognized by IgG1 and IgG3 antibodies from individuals putatively resistant to schistosome infection, but not chronically infected people, and to induce high levels of protection against challenge infection in the murine model of schistosomiasis. Amplification by PCR of homologous sequences from male and female S. japonicum worms showed the presence of 7 different clusters or subclasses of S. japonicum TSP-2. We determined the protective efficacy of one subclass - Sj-TSP-2e.

Methodology/principal findings: Following the alignment of 211 cDNAs, we identified 7 clusters encoding S. japonicum TSP-2 (Sj-TSP-2) based on sequence variation in the large extracellular loop (LEL) region with differing frequency of transcription in male and female worms. Quantitative PCR analysis revealed elevated expression of Sj-TSP-2 in adult worms compared with other life cycle stages. We expressed in E. coli the LEL region of one of the clusters which exhibited a high frequency of transcription in female worms, and showed the purified recombinant protein (Sj-TSP-2e) was recognised by 43.1% of sera obtained from confirmed schistosomiasis japonica patients. Vaccination of mice with the recombinant protein induced high levels of IgG1 and IgG2 antibodies, but no consistent protective efficacy against challenge infection was elicited in three independent trials.

Conclusions/significance: The highly polymorphic nature of the Sj-TSP-2 gene at the transcriptional level may limit the value of Sj-TSP-2 as a target for future S. japonicum vaccine development.

Show MeSH
Related in: MedlinePlus