EDCTP Alumni Network

Fostering excellence and collaboration in the next generation of researchers

Call Career Development Fellowship (CDF)
Programme EDCTP2
Start Date 2021-09-01
End Date 2024-08-31
Project Code TMA2020CDF-3158
Status Active

Title

Characterization of protein and glycan epitopes recognised following controlled human infection with Schistosoma mansoni in an endemic population.

Host Organisation

Institution Country
Uganda National Health Research Organisation (UNHRO) Uganda

Current Organisation

MRC/UVRI and LSHTM Uganda Research Unit

Current Job Title

Scientist A

Areas Of Specialisation

Neglected Infectious Diseases (NID)

Grants

Grant Code:
Source of funding:
GCRF
Amount:
28166
Role:
Postdoc Research Associate
Start Date:
2020-01-01
End Date:
2020-01-01
Grant Code:
Source of funding:
GCRF
Amount:
21972.00
Role:
Postdoc Research Associate
Start Date:
2019-01-01
End Date:
2019-01-01
Grant Code:
Source of funding:
MRC
Amount:
24985
Role:
Co-investigator
Start Date:
2020-01-01
End Date:
2021-01-01
Grant Code:
Source of funding:
MRC Uganda
Amount:
34118
Role:
Researcher
Start Date:
2020-01-01
End Date:
2021-01-01

Publications

Authors:
Joyce Namulondo
Date:
2021-12-08
Journal:
AAS Open Research
Content:

Schistosomiasis affects over 250 million people worldwide with an estimated mortality of more than 200,000 deaths per year in subSaharan Africa. Efforts to control schistosomiasis in the affected areas have mainly relied on the mass administration of praziquantel, which kills adult but not immature worms of all Schistosoma species. Mammalian hosts respond differently to Schistosoma infection with some being more susceptible than others, which is associated with risk factors such as sociodemographic, epidemiological, immunological, and/or genetic. Host genetic factors play a major role in influencing molecular processes in response to schistosomiasis as shown in gene expression studies. These studies highlight gene profiles expressed at different time points of infection using model animals. Immune function-related genes; cytokines (Th1 and Th17) are upregulated earlier in infection and Th2 upregulated later indicating a mixed Th1/Th2 response. However, Th1 response has been shown to be sustained in S. japonicum infection. Immune mediators such as matrix metalloproteinases (Mmps) and tissue inhibitors of matrix metalloproteinases (Timps) are expressed later in the infection and these are linked to wound healing and fibrosis. Downregulation of metabolic associated genes is recorded in later stages of infection. Most mammalian host gene expression studies have been done using rodent models, with fewer in larger hosts such as bovines and humans. The majority of these studies have focused on S. japonicum infections and less on S. haematobium and S. mansoni infections (the two species that cause most global infections). The few human schistosomiasis gene expression studies so far have focused on S. japonicum and S. haematobium infections and none on S. mansoni, as far as we are aware. This highlights a paucity of gene expression data in humans, specifically with S. mansoni infection. This data is important to understand the disease pathology, identify biomarkers, diagnostics and possible drug targets.

Identifiers:
Funded by Not Informed: not informed
Authors:
Moses Egesa
Date:
2017-08-14
Journal:
Trends in Parasitology
Content:

There is currently no vaccine against schistosomiasis. With few Schistosoma vaccine candidates in clinical trials, unexplored antigens from the vulnerable schistosomulum should be considered as possible vaccine candidates. In addition, we suggest developing synthetic vesicles as a new delivery vehicle and adjuvant for immunoprophylactic schistosomula vaccine candidates.

Identifiers:
28818406: not informed
Authors:
Moses Egesa
Date:
2018-09-21
Journal:
Parasite Immunology
Content:

Larvae of Schistosoma (schistosomula) are highly susceptible to host immune responses and are attractive prophylactic vaccine targets, although cellular immune responses against schistosomula antigens in endemic human populations are not well characterized. We collected blood and stool from 54 Schistosoma mansoni-infected Ugandans, isolated peripheral blood mononuclear cells, and stimulated them for 24 hours with schistosome adult worm and soluble egg antigens (AWA and SEA), along with schistosomula recombinant proteins rSmKK7, Lymphocyte Antigen 6 iso- forms (rSmLy6A and rSmLy6B), tetraspanin isoforms (rSmTSP6 and rSmTSP7). Cytokines, chemokines, and growth factors were measured in the culture supernatants using a multiplex Luminex assay, and infection intensity was determined before and at 1 year after praziquantel (PZQ) treatment using the Kato-Katz method. Cellular responses were grouped and the relationship between groups of correlated cellular responses and infection intensity before and after PZQ treatment was investigated. AWA and SEA induced mainly Th2 responses. In contrast, rSmLy6B, rSmTSP6 and rSmTSP7 induced Th1/pro-inflammatory responses. While recombinant antigens rSmKK7 and rSmLy6A did not induce a Th1/pro-inflammatory response, they had an association with pre-treatment infection intensity after adjusting for age and sex. Testing more schistosomula antigens using this approach could provide immune- epidemiology identifiers necessary for prioritizing next-generation schistosomiasis vaccine candidates.

Identifiers:
Not Informed: not informed
Authors:
Moses Egesa
Date:
2018-09-21
Journal:
Parasite Immunology
Content:

While antigens from Schistosoma schistosomula have been suggested as potential vaccine candidates, the association between antibody responses with schistosomula antigens and infection intensity at reinfection is not well known. Schistosoma mansoni-infected individuals were recruited from a schistosomiasis endemic area in Uganda (n = 372), treated with 40 mg/kg praziquantel (PZQ) and followed up at five weeks and at one year post-treatment. Pre-treatment and five weeks post-treatment immunoglobulin (Ig) E, IgG1 and IgG4 levels against recombinant schistosomula antigens rSmKK7, rSmLy6A, rSmLy6B and rSmTSP7 were measured using ELISA. Factors associated with detectable pre-treatment or post-treatment antibody response against the schistosomula antigens and the association between five-week antibody responses and one year post-treatment reinfection intensity among antibody responders were examined. Being male was associated with higher pre-treatment IgG1 to rSmKK7, rSmLy6a and AWA. Five weeks post-treatment antibody responses against schistosomula antigens were not associated with one year post-treatment reinfection intensity among antibody responders’ antibody levels against rSmKK7, rSmLy6B and rSmTSP7 dropped, but increased against rSmLy6A, AWA and SEA at five weeks post-treatment among antibody responders. S. mansoni-infected individuals exhibit detectable antibody responses to schistosomula antigens that are affected by treatment. These findings indicate that schistosomula antigens induce highly varied antibody responses and could have implications for vaccine development.

Identifiers:
30239012: not informed

Projects

Fellow:
Moses Egesa
Collaborators:
Name Country Institution
Prof Alison Elliott United Kingdom LSHTM
Objectives:
Primary objective: To investigate (1) the safety and tolerability and (2) the infectivity of male Schistosoma mansoni (Sm) cercariae in healthy adult Ugandan volunteers with (a) minimal prior exposure to Sm, and (b) intense prior exposure to Sm. Exploratory objectives: To investigate the kinetics of controlled infection with male Schistosoma mansoni cercariae in healthy adult Ugandan volunteers (a) with minimal prior exposure to Sm, and (b) with intense prior exposure to Sm. To investigate immunological, metabolic and microbiome changes after infection with Schistosoma mansoni male cercariae. To investigate volunteer and wider community understandings of CHI in the context of CHI-S
Sites:
Two Ugandan communities, one with minimal and one with intense prior schistosome exposure
Study Design:
Open label intervention study
Subjects:
Healthy Volunteers
Start Date:
2020-08-01
End Date:
2025-07-31

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