Inconsistent Protective Efficacy and Marked Polymorphism Limits the Value of Schistosoma japonicum Tetraspanin-2 as a Vaccine Target

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 FindingsFollowing 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/SignificanceThe 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.

A Transcriptomic Analysis of Echinococcus granulosus Larval Stages: Implications for Parasite Biology and Host Adaptation

“…Novel TSPs may thus have evolved to fulfill the highly diverse requirements of distinct parasite stages. In this context, it is worth noting that TSPs have been assayed as vaccine antigens for schistosomiasis [126], [127] and primary alveolar echinococcosis [119] in mouse models. In both systems, some level of protection was observed upon immunization with particular TSPs.…”

Single multivalent vaccination boosted by trickle larval infection confers protection against experimental lymphatic filariasis

“…When BmALT-2 was combined with BmHSP12.6 (14) and BmTSP-LEL as a multivalent fusion vaccine, close to 95% protection were achieved in mouse and gerbil models (15). Gene polymorphism has been reported for TSP-2 from S. japonicum (27,28). However, to date there are no reports on the gene polymorphism of B. malayi or W. bancrofti TSP-2.…”

A next-generation microarray further reveals stage-enriched gene expression pattern in the blood fluke Schistosoma japonicum

“…On invading a mammalian host, schistosomes have evolved several mechanisms to adapt to, and survive in, the hostile host environment; in particular, they develop a unique syncytial tegument, as well as mechanisms of antigenic mimicry [33], immune modulation [68] and evasion [69, 70]. In this study, we found extracellular matrix constituents, that are located in the tegumental protein assemblage, were enriched in hepatic schistosomula.…”