Authors

Discussion

The zoonotic nature of schistosomiasis in Southeast Asia, caused by Schistosoma japonicum, is arguably the most challenging factor hindering schistosomiasis control and elimination in the region. S. japonicum infects > 40 different mammalian hosts, however, the precise impact of wild and domesticated animals acting as reservoirs of infection, in maintaining transmission cycles, and promoting parasite diversification, remains unclear. Zoonotic pathogen interactions within hosts likely impact and alter pathogen evolution and may have implications for control and elimination goals. It is generally thought that parasite populations that infect multiple hosts can evolve novel, host-specific, Antigen Coding Genes (ACGs), and can become increasingly virulent when infecting different host species. In other pathogens, the diversification of ACGs has been implicated in alterations in the ability of the parasite to evade detection, and thus the ability of the host’s immune system to recognise infection.  

This work focuses on the variation and genetic diversity of the tegumental-surface antigen tetraspanin-23 (SjTSP-23) within and between definitive host species. SjTSP-23 is integral to parasite survival in the definitive host and has been shown to interact directly with the definitive host’s immune system via their Large Extracellular Loop (LEL) domains, and is thus regarded as a potential vaccine candidate. 

Sequencing SjTSP-23-LEL domains from 81 FTA-archived S. japonicum miracidia from four definitive host species (human, dog, cat, and pig), has enabled the variation and frequency of parasite ACG genotypes from human and animal host populations, and the identification of shared antigen variants, to be investigated. It is expected that SjTSP-23-LEL sampled from human hosts would be more genetically diverse than those sampled from other host species, and that this increased variation will have structural, functional, and antibody-binding consequences, possibly leading to challenges with downstream vaccine design and development. 

Through investigating the phylogenetic relationships and distribution of SjTSP-23-LEL haplotypes among definitive hosts, it was found that although humans contain the greatest frequency of unique, divergent haplotypes, there is significant sharing of antigen variants between hosts, with antigens predicted to be more genetically variable within host populations than between them. Furthermore, the selection pressures acting on sites within the LEL domain of SjTSP-23 from all hosts induced amino acid changes and antigenic variation in and around predicted antibody binding-sites, suggesting that host-derived selection pressures driving amino acid changes may serve as ‘escape mutations’, acting to reduce SjTSP-23-LEL antigenicity as an immune evasion mechanism.