Evolution of tetraspanin antigens in the zoonotic Asian blood fluke Schistosoma japonicum
Abstract Background Despite successful control efforts in China over the past 60 years, zoonotic schistosomiasis caused by Schistosoma japonicum remains a threat with transmission ongoing and the risk of localised resurgences prompting calls for a novel integrated control strategy, with an anti-schi...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-03-01
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| Series: | Parasites & Vectors |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13071-023-05706-3 |
| _version_ | 1797865379128672256 |
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| author | Daniel A. J. Parsons Anthony J. Walker Aidan M. Emery Joanne P. Webster Scott P. Lawton |
| author_facet | Daniel A. J. Parsons Anthony J. Walker Aidan M. Emery Joanne P. Webster Scott P. Lawton |
| author_sort | Daniel A. J. Parsons |
| collection | DOAJ |
| description | Abstract Background Despite successful control efforts in China over the past 60 years, zoonotic schistosomiasis caused by Schistosoma japonicum remains a threat with transmission ongoing and the risk of localised resurgences prompting calls for a novel integrated control strategy, with an anti-schistosome vaccine as a core element. Anti-schistosome vaccine development and immunisation attempts in non-human mammalian host species, intended to interrupt transmission, and utilising various antigen targets, have yielded mixed success, with some studies highlighting variation in schistosome antigen coding genes (ACGs) as possible confounders of vaccine efficacy. Thus, robust selection of target ACGs, including assessment of their genetic diversity and antigenic variability, is paramount. Tetraspanins (TSPs), a family of tegument-surface antigens in schistosomes, interact directly with the host’s immune system and are promising vaccine candidates. Here, for the first time to our knowledge, diversity in S. japonicum TSPs (SjTSPs) and the impact of diversifying selection and sequence variation on immunogenicity in these protiens were evaluated. Methods SjTSP sequences, representing parasite populations from seven provinces across China, were gathered by baiting published short-read NGS data and were analysed using in silico methods to measure sequence variation and selection pressures and predict the impact of selection on variation in antigen protein structure, function and antigenic propensity. Results Here, 27 SjTSPs were identified across three subfamilies, highlighting the diversity of TSPs in S. japonicum. Considerable variation was demonstrated for several SjTSPs between geographical regions/provinces, revealing that episodic, diversifying positive selection pressures promote amino acid variation/variability in the large extracellular loop (LEL) domain of certain SjTSPs. Accumulating polymorphisms in the LEL domain of SjTSP-2, -8 and -23 led to altered structural, functional and antibody binding characteristics, which are predicted to impact antibody recognition and possibly blunt the host’s ability to respond to infection. Such changes, therefore, appear to represent a mechanism utilised by S. japonicum to evade the host’s immune system. Conclusion Whilst the genetic and antigenic geographic variability observed amongst certain SjTSPs could present challenges to vaccine development, here we demonstrate conservation amongst SjTSP-1, -13 and -14, revealing their likely improved utility as efficacious vaccine candidates. Importantly, our data highlight that robust evaluation of vaccine target variability in natural parasite populations should be a prerequisite for anti-schistosome vaccine development. Graphical abstract |
| first_indexed | 2024-04-09T23:08:10Z |
| format | Article |
| id | doaj.art-131520088d374b438b7fde2994436fb1 |
| institution | Directory Open Access Journal |
| issn | 1756-3305 |
| language | English |
| last_indexed | 2024-04-09T23:08:10Z |
| publishDate | 2023-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Parasites & Vectors |
| spelling | doaj.art-131520088d374b438b7fde2994436fb12023-03-22T10:33:49ZengBMCParasites & Vectors1756-33052023-03-0116111710.1186/s13071-023-05706-3Evolution of tetraspanin antigens in the zoonotic Asian blood fluke Schistosoma japonicumDaniel A. J. Parsons0Anthony J. Walker1Aidan M. Emery2Joanne P. Webster3Scott P. Lawton4Molecular Parasitology Laboratory, School of Life Sciences, Pharmacy and Chemistry, Kingston University LondonMolecular Parasitology Laboratory, School of Life Sciences, Pharmacy and Chemistry, Kingston University LondonDepartment of Life Sciences, Natural History MuseumDepartment of Pathobiology and Population Sciences, Royal Veterinary College, University of London, Hawkshead CampusCentre for Epidemiology & Planetary Health, Department of Veterinary and Animal Sciences, Northern Faculty, Scotland’s Rural CollegeAbstract Background Despite successful control efforts in China over the past 60 years, zoonotic schistosomiasis caused by Schistosoma japonicum remains a threat with transmission ongoing and the risk of localised resurgences prompting calls for a novel integrated control strategy, with an anti-schistosome vaccine as a core element. Anti-schistosome vaccine development and immunisation attempts in non-human mammalian host species, intended to interrupt transmission, and utilising various antigen targets, have yielded mixed success, with some studies highlighting variation in schistosome antigen coding genes (ACGs) as possible confounders of vaccine efficacy. Thus, robust selection of target ACGs, including assessment of their genetic diversity and antigenic variability, is paramount. Tetraspanins (TSPs), a family of tegument-surface antigens in schistosomes, interact directly with the host’s immune system and are promising vaccine candidates. Here, for the first time to our knowledge, diversity in S. japonicum TSPs (SjTSPs) and the impact of diversifying selection and sequence variation on immunogenicity in these protiens were evaluated. Methods SjTSP sequences, representing parasite populations from seven provinces across China, were gathered by baiting published short-read NGS data and were analysed using in silico methods to measure sequence variation and selection pressures and predict the impact of selection on variation in antigen protein structure, function and antigenic propensity. Results Here, 27 SjTSPs were identified across three subfamilies, highlighting the diversity of TSPs in S. japonicum. Considerable variation was demonstrated for several SjTSPs between geographical regions/provinces, revealing that episodic, diversifying positive selection pressures promote amino acid variation/variability in the large extracellular loop (LEL) domain of certain SjTSPs. Accumulating polymorphisms in the LEL domain of SjTSP-2, -8 and -23 led to altered structural, functional and antibody binding characteristics, which are predicted to impact antibody recognition and possibly blunt the host’s ability to respond to infection. Such changes, therefore, appear to represent a mechanism utilised by S. japonicum to evade the host’s immune system. Conclusion Whilst the genetic and antigenic geographic variability observed amongst certain SjTSPs could present challenges to vaccine development, here we demonstrate conservation amongst SjTSP-1, -13 and -14, revealing their likely improved utility as efficacious vaccine candidates. Importantly, our data highlight that robust evaluation of vaccine target variability in natural parasite populations should be a prerequisite for anti-schistosome vaccine development. Graphical abstracthttps://doi.org/10.1186/s13071-023-05706-3Schistosoma japonicumChinaTetraspaninVaccine candidateSelection pressuresImmune evasion |
| spellingShingle | Daniel A. J. Parsons Anthony J. Walker Aidan M. Emery Joanne P. Webster Scott P. Lawton Evolution of tetraspanin antigens in the zoonotic Asian blood fluke Schistosoma japonicum Parasites & Vectors Schistosoma japonicum China Tetraspanin Vaccine candidate Selection pressures Immune evasion |
| title | Evolution of tetraspanin antigens in the zoonotic Asian blood fluke Schistosoma japonicum |
| title_full | Evolution of tetraspanin antigens in the zoonotic Asian blood fluke Schistosoma japonicum |
| title_fullStr | Evolution of tetraspanin antigens in the zoonotic Asian blood fluke Schistosoma japonicum |
| title_full_unstemmed | Evolution of tetraspanin antigens in the zoonotic Asian blood fluke Schistosoma japonicum |
| title_short | Evolution of tetraspanin antigens in the zoonotic Asian blood fluke Schistosoma japonicum |
| title_sort | evolution of tetraspanin antigens in the zoonotic asian blood fluke schistosoma japonicum |
| topic | Schistosoma japonicum China Tetraspanin Vaccine candidate Selection pressures Immune evasion |
| url | https://doi.org/10.1186/s13071-023-05706-3 |
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