Schistosomiasis: From Immunopathology to Vaccines

A special issue of Pathogens (ISSN 2076-0817). This special issue belongs to the section "Vaccines and Therapeutic Developments".

Deadline for manuscript submissions: 28 February 2025 | Viewed by 6430

Special Issue Editors


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Guest Editor
Department of Tropical Medicine and Infectious Diseases, Center of Internal Medicine II, University Medical Center Rostock, 18057 Rostock, Germany
Interests: schistosomiasis immuno-pathology; host–parasite interaction; anti-fibrotic therapy; single-sex infection

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Guest Editor
Department of Tropical Medicine and Infectious Diseases, Center of Internal Medicine II, University Medical Center Rostock, 18057 Rostock, Germany
Interests: schistosomiasis; tropical medicine; clinical trials; vaccine development

Special Issue Information

Dear Colleagues,

It is our pleasure to invite you to contribute articles to the upcoming Special Issue of Pathogens, entitled “Schistosomiasis: From Immunopathology to Vaccines”. 

In the 21st century, schistosomiasis remains one of the most common parasitic tropical diseases [1]. The clinical picture is characterized primarily by the host–immune response to schistosome eggs entrapped in tissues and the granulomatous inflammatory and fibrosing reaction they trigger [2-4]. In 2018, WHO estimated that almost 240 million people were infected by Schistosoma spp., mainly residing in Africa (South Africa), Middle East and South America [5]. Most endemic areas are among the least developed countries, whose health systems face difficulties to provide basic care at the primary health level. However, attention has also recently been attracted by confirmed cases of human schistosomiasis, reintroduced to Southern Europe, Corsica [6] and Spain [7], which indicate a potential public health threat emerging, even in western industrialized countries, due to climate change and human migration [8]. 

As there is currently no vaccine available to combat schistosomiasis, drug treatment stands as the sole therapeutic alternative. Praziquantel, an anthelminthic drug, is recommended for treatment, but it does not provide protection against reinfection. Unfortunately, it is difficult to prevent infection in areas where schistosomiasis is endemic [9]. As a result, there is significant pressure to research schistosomiasis and develop a vaccine against the multicellular parasite Schistosoma spp. to prevent reinfection in endemic areas, particularly in children, and reduce transmission. A vaccine against Schistosoma spp. is regarded as one of the top 10 urgently needed vaccines which remain yet to be developed [10].

This Special Issue is intended act as a depository for the compilation of articles that present the up-to-date picture of vaccine development and related research. Original articles and reviews, addressing the following topics and research aspects, are welcome:

  • Updates on Schistosoma vaccine clinical trials in the laboratory and in the field.
  • Basic research on increasing resistance to infection against Schistosoma spp. in different animal models
  • Challenges in vaccine development against Schistosoma spp.
  • New vaccine candidates and Omics-technology to identify new targets against Schistosoma spp.
  • Advances in vaccine development against Schistosoma spp.: from protein to mRNA vaccines 
  • Immunization and infection status in special populations (immunocompromised, pregnant, co-morbidities, and infections)
  • Immunizing efficacy of drugs not primarily directed against schistosomes

1.    GBD 2016 DALYs and HALE Collaborators. Global, regional, and national disability-adjusted life-years (DALYs) for 333 diseases and injuries and healthy life expectancy (HALE) for 195 countries and territories, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet 390, 1260–1344 (2017).
2.    Bica, I., D.H. Hamer, and M.J. Stadecker, Hepatic schistosomiasis. Infect Dis Clin North Am, 2000. 14(3): p. 583-604, viii.
3.    Stadecker, M.J., et al., The immunobiology of Th1 polarization in high-pathology schistosomiasis. Immunol Rev, 2004. 201: p. 168-79.
4.    Burke, M.L., et al., Immunopathogenesis of human schistosomiasis. Parasite Immunol, 2009. 31(4): p. 163-76.
5.    WHO, 2019. Schistosomiasis and soil-transmitted helminthiases: number of people treated in 2018. Weekly epidemiological record 50(13).
6.    Ramalli, L., et al., Persistence of schistosomal transmission linked to the Cavu river in southern Corsica since 2013. Euro Surveill, 2018. 23(4).
7.    Salas-Coronas, J., et al., Evidence of autochthonous transmission of urinary schistosomiasis in Almeria (southeast Spain): An outbreak analysis. Travel Med Infect Dis, 2021. 44: p. 102165.
8.    Kalinda, C., M. Chimbari, and S. Mukaratirwa, Implications of Changing Temperatures on the Growth, Fecundity and Survival of Intermediate Host Snails of Schistosomiasis: A Systematic Review. Int J Environ Res Public Health, 2017. 14(1).
9.    Sabah, A.A., et al., Schistosoma mansoni: chemotherapy of infections of different ages. Exp Parasitol, 1986. 61(3): p. 294-303.
10.    Cohen, J., Unfilled Vials. Science, 2016. 351(6268): p. 16-9.

Dr. Martina Sombetzki
Prof. Dr. Emil Christian Reisinger
Guest Editors

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Published Papers (4 papers)

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Research

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19 pages, 8515 KiB  
Article
Computational Workflow to Design Novel Vaccine Candidates and Small-Molecule Therapeutics for Schistosomiasis
by Emmanuel Oluwadare Balogun, Gideon Ibrahim Joseph, Samuel Charles Olabode, Naziru Abdulkadir Dayaso, Ammar Usman Danazumi, Rachael Bashford-Rogers, James H. Mckerrow, Ghulam Jeelani and Conor R. Caffrey
Pathogens 2024, 13(10), 850; https://doi.org/10.3390/pathogens13100850 - 30 Sep 2024
Viewed by 1276
Abstract
Human schistosomiasis, caused by the Schistosoma trematode, is a neglected parasitic disease affecting over 250 million people worldwide. There is no vaccine, and the single available drug is threatened by drug resistance. This study presents a computational approach to designing multiepitope vaccines (MEVs) [...] Read more.
Human schistosomiasis, caused by the Schistosoma trematode, is a neglected parasitic disease affecting over 250 million people worldwide. There is no vaccine, and the single available drug is threatened by drug resistance. This study presents a computational approach to designing multiepitope vaccines (MEVs) targeting the cercarial (CMEV) and schistosomular (SMEV) stages of schistosomes, and identifies potential schistosomicidal compounds from the Medicine for Malaria Ventures (MMV) and SuperNatural Database (SND) libraries. The designed vaccines (CMEV and SMEV) are engineered to provoke robust immune responses by incorporating a blend of T- and B-cell epitopes. Structural and immunoinformatics evaluations predicted robust interactions of CMEV and SMEV with key immune receptors and prolonged immune responses. In addition, molecular docking identified several compounds from the MMV and SND libraries with strong binding affinities to vital Schistosoma cathepsin proteases, indicating their potential as schistosomicidal agents. Our findings contribute to the potential development of effective vaccines and drugs against schistosomiasis. Full article
(This article belongs to the Special Issue Schistosomiasis: From Immunopathology to Vaccines)
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13 pages, 2320 KiB  
Article
Individually or as a Team—The Immunological Milieu in the Lung Caused by Migrating Single-Sex or Mixed-Sex Larvae of Schistosoma mansoni
by Miriam Bischofsberger, Cindy Reinholdt, Tim Alexander Dannenhaus, Johann Aleith, Wendy Bergmann-Ewert, Brigitte Müller-Hilke, Micha Löbermann, Emil C. Reisinger and Martina Sombetzki
Pathogens 2023, 12(12), 1432; https://doi.org/10.3390/pathogens12121432 - 8 Dec 2023
Cited by 1 | Viewed by 1503
Abstract
While the lung is considered an efficient site for stopping the larvae of the acute Schistosoma spp. infection phase from migrating through extensive inflammatory responses in the surrounding tissues, little is known about these processes. To date, the highest resistance to infection has [...] Read more.
While the lung is considered an efficient site for stopping the larvae of the acute Schistosoma spp. infection phase from migrating through extensive inflammatory responses in the surrounding tissues, little is known about these processes. To date, the highest resistance to infection has been achieved in experimental studies with radiation-attenuated cercariae immunization, which elicits a strong Th1/Th2 response in the lung and results in up to 80% protection. Based on our own studies demonstrating a systemic, unpolarized Th1/Th2 response resulting from infection with male or female Schistosoma mansoni, we hypothesize that this atypical immune response is already detectable during the pulmonary passage of parasite larvae. Therefore, we examined the immune milieu in the lungs of mice caused by migrating schistosome larvae, either male or female (single-sex groups) or male + female (bisexual control), 4 and 16 days after infection in bronchoalveolar lavage and lung tissue by flow cytometry, qPCR, and multiplex analyzes. Our results show only minor differences in the inflammatory profile between the single-sex groups but significant differences compared with the bisexual control group. Both single-sex infected groups have increased expression of inflammatory markers in lung tissue, higher numbers of cytotoxic T cells (day 4 post-infection) and more T helper cells (day 16 post-infection), compared with the bisexual control group. A single-sex infection, regardless of whether it is an infection with male or female cercariae, causes an immune milieu in the lung that is clearly different from an infection with both sexes. In terms of identifying therapeutic targets to achieve resistance to re-infection, it is of great scientific interest to identify the differences in the inflammatory potential of male or female and male + female parasites. Full article
(This article belongs to the Special Issue Schistosomiasis: From Immunopathology to Vaccines)
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Review

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15 pages, 328 KiB  
Review
Models of Protective Immunity against Schistosomes: Implications for Vaccine Development
by R Alan Wilson
Pathogens 2023, 12(10), 1215; https://doi.org/10.3390/pathogens12101215 - 3 Oct 2023
Cited by 2 | Viewed by 1729
Abstract
After many decades of research, a schistosome vaccine still looks to be a distant prospect. These helminths can live in the human bloodstream for years, even decades, surrounded by and feeding on the components of the immune response they provoke. The original idea [...] Read more.
After many decades of research, a schistosome vaccine still looks to be a distant prospect. These helminths can live in the human bloodstream for years, even decades, surrounded by and feeding on the components of the immune response they provoke. The original idea of a vaccine based on the killing of invading cercariae in the skin has proven to be illusory. There has also been a realisation that even if humans develop some protection against infection over a protracted period, it very likely involves IgE-mediated responses that cannot provide the basis for a vaccine. However, it has also become clear that both invasive migrating larvae and adult worms must expose proteins and release secretions into the host environment as part of their normal biological activities. The application of modern ‘omics approaches means that we now have a much better idea of the identity of these potential immune targets. This review looks at three animal models in which acquired immunity has been demonstrated and asks whether the mechanisms might inform our vaccine strategies to achieve protection in model hosts and humans. Eliciting responses, either humoral or cellular, that can persist for many months is a challenge. Arming of the lungs with effector T cells, as occurs in mice exposed to the radiation-attenuated cercarial vaccine, is one avenue. Generating IgG antibody titres that reach levels at which they can exert sustained immune pressure to cause worm elimination, as occurs in rhesus macaques, is another. The induction of memory cell populations that can detect trickle invasions of larval stages remains to be explored. One promising approach is the analysis of protective antibodies using high-density peptide arrays of target proteins to identify reactive regions. These can be combined in multi-epitope constructs to immunise a host against many targets simultaneously and cheaply. Full article
(This article belongs to the Special Issue Schistosomiasis: From Immunopathology to Vaccines)

Other

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8 pages, 836 KiB  
Systematic Review
Human Placental Schistosomiasis—A Systematic Review of the Literature
by Jacob Gerstenberg, Sasmita Mishra, Martha Holtfreter, Joachim Richter, Saskia Dede Davi, Dearie Glory Okwu, Michael Ramharter, Johannes Mischlinger and Benjamin T. Schleenvoigt
Pathogens 2024, 13(6), 470; https://doi.org/10.3390/pathogens13060470 - 3 Jun 2024
Cited by 2 | Viewed by 1297
Abstract
Background: Schistosome egg deposition in pregnant women may affect the placenta of infected mothers and cause placental schistosomiasis (PS). Histopathological examination of placental tissue is an inadequate detection method due to low sensitivity. So far, there has not been any systematic review on [...] Read more.
Background: Schistosome egg deposition in pregnant women may affect the placenta of infected mothers and cause placental schistosomiasis (PS). Histopathological examination of placental tissue is an inadequate detection method due to low sensitivity. So far, there has not been any systematic review on PS. Methods: We conducted a systematic literature search on PubMed, EMBASE, and Medline and included all publications that reported microscopically confirmed cases of PS, as well as the relevant secondary literature found in the citations of the primarily included publications. Results: Out of 113 abstracts screened we found a total of 8 publications describing PS with a total of 92 cases describing egg deposition of dead and/or viable eggs and worms of S. haematobium and S. mansoni in placental tissue. One cross-sectional study investigating the prevalence of PS and its association with adverse birth outcomes, found 22% of placentas to be infested using a maceration technique but only <1% using histologic examination. Additionally, no direct link to deleterious pregnancy outcomes could be shown. Conclusions: PS is a highly unattended and underdiagnosed condition in endemic populations, due to a lack of awareness as well as low sensitivity of histopathological examinations. However, PS may play an important role in mediating or reinforcing adverse birth outcomes (ABO) such as fetal growth restriction (FGR) in maternal schistosomiasis, possibly by placental inflammation. Full article
(This article belongs to the Special Issue Schistosomiasis: From Immunopathology to Vaccines)
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