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

Zhang, Wenbao, Li, Jun, Duke, Mary, Jones, Malcolm K, Kuang, Ling, Zhang, Jianfeng, Blair, David, Li, Yuesheng and McManus, Donald P. (2011) Inconsistent protective efficacy and marked polymorphism limits the value of Schistosoma japonicum Tetraspanin-2 as a vaccine target. PLoS Neglected Tropical Diseases, 5 5: e1166-1-e1166-11. doi:10.1371/journal.pntd.0001166


Author Zhang, Wenbao
Li, Jun
Duke, Mary
Jones, Malcolm K
Kuang, Ling
Zhang, Jianfeng
Blair, David
Li, Yuesheng
McManus, Donald P.
Title Inconsistent protective efficacy and marked polymorphism limits the value of Schistosoma japonicum Tetraspanin-2 as a vaccine target
Journal name PLoS Neglected Tropical Diseases   Check publisher's open access policy
ISSN 1935-2727
1935-2735
Publication date 2011-05-01
Sub-type Article (original research)
DOI 10.1371/journal.pntd.0001166
Open Access Status DOI
Volume 5
Issue 5
Start page e1166-1
End page e1166-11
Total pages 11
Place of publication San Francisco, CA, United States
Publisher Public Library of Science
Collection year 2012
Language eng
Formatted 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.
Keyword Mansoni
Echinococcosis
Resistance
Parasite
Proteins
Immunity
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Article # e1166 Received: December 20, 2010; Accepted: March 16, 2011; Published: May 31, 2011

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2012 Collection
School of Veterinary Science Publications
 
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