Experimental approach

Study design

A longitudinal study design will be used. SmCHI Epitope is nested within the CHI-S-Ug study that is a dose-escalation controlled human S. mansoni infection study and a vaccine trial with a promising schistosomiasis vaccine candidate.

For the SmCHI Epitope, CHI-S-Ug volunteers will be grouped as “putatively resistant” or “susceptible” to CHI-S depending on the levels of CAA. In the majority of schistosomiasis- naive CHI-S volunteers, the infection was detectable six weeks after challenge using the CAA test. To relate antibody responses with protection against controlled human infection, the volunteers will be stratified by the dose of S. mansoni cercariae given.

Laboratory methods

Characterize antibody responses to recombinant proteins and peptide epitopes of surface-exposed and secreted proteins of S. mansoni before CHI-S and relate this to whether volunteers get infected or not following exposure to CHI-S. Human serum will be screened sequentially using two complementary screens to examine the reactivity of CHI-S volunteer sera. First, a library of recombinant proteins will be screened for IgG and IgE by ELISA with sera collected before and after the CHI-S. Sera from non-exposed European controls will be included in the ELISA runs. The main focus will be on tegumental and secretory S. mansoni proteins. The proteins will be expressed using a mammalian expression system and will be performed with support from Dr Cecile Crosnier at the University of York. ELISA antibody responses will be compared between volunteers who are putatively resistant (N=15) and susceptible (N=15) to CHI-S.

Secondly, a custom-made peptide array will be used to screen for epitopes in the ten most reactive proteins by ELISA mentioned above. IgG and IgE antibody responses will be compared, using this array, at three time-points: before infection, during infection (and before treatment) and after treatment. Peptide array protocols in use with sera of animal models of schistosomiasis at the University of York will be adapted for use with sera of humans infected with S. mansoni under the supervision of Dr. James Hewitson and Prof. Alan Wilson.

Investigate the specific anti-glycan antibody responses before CHI-S and relate this to whether volunteers get infected or not following exposure to CHI-S. A glycan microarray will be used to screen sera before and after the CHI-S in 30 individuals. Anti-glycan IgG and IgM responses at Week 6 will be compared between volunteers who are putatively resistant (N=15) and susceptible (N=15) to CHI-S. Microarrays containing natural glycans isolated from different life stages of Schistosoma glycans/glycoconjugates will be generated and IgG and IgM antibodies measured. Antibody responses will also be compared before and after treatment. Anti-glycan antibody levels in endemic CHI-S volunteers will be compared with related findings from Dutch volunteers. This work will be carried out in collaboration with Prof. Cornelis Hokke and Dr. Angela van Diepen of the Glycobiology Group at the Department of Parasitology, Leiden University Medical Center (LUMC)