Abstract
Controlled human infection (CHI) models are gaining recognition as an approach to accelerating vaccine development, for use in both non-endemic and endemic populations: they can facilitate identification of the most promising candidate vaccines for further trials and advance understanding of protective immunity. Helminths present a continuing health burden in sub-Saharan Africa. Vaccine development for these complex organisms is particularly challenging, partly because protective responses are akin to mechanisms of allergy. A CHI model for Schistosoma mansoni (CHI-S) has been developed at Leiden University Medical Centre, the Netherlands. However, responses to schistosome infections, and candidate vaccines, are likely to be different among people from endemic settings compared to schistosome-naïve Dutch volunteers. Furthermore, among volunteers from endemic regions who have acquired immune responses through prior exposure, schistosome challenge can be used to define responses associated with clinical protection, and thus to guide vaccine development. To explore the possibility of establishing the CHI-S in Uganda, a Stakeholders' Meeting was held in Entebbe in 2017. Regulators, community members, researchers and policy-makers discussed implementation challenges and recommended preparatory steps: risk assessment; development of infrastructure and technical capacity to produce the infectious challenge material in Uganda; community engagement from Parliamentary to grass-roots level; pilot studies to establish approaches to assuring fully informed consent and true voluntariness, and strategies for selection of volunteers who can avoid natural infection during the 12-week CHI-S; the building of regulatory capacity; and the development of study protocols and a product dossier in close consultation with ethical and regulatory partners. It was recommended that, on completion, the protocol and product dossier be reviewed for approval in a joint meeting combining ethical, regulatory and environment management authorities. Most importantly, representatives of schistosomiasis-affected communities emphasised the urgent need for an effective vaccine and urged the research community not to delay in the development process.
Highlights
Effective vaccines have proven extremely useful in the prevention of infectious diseases, but are still lacking for major poverty-related and neglected infections, including helminth infections
The current approach to control schistosomiasis is through mass drug administration (MDA) with praziquantel, but this is limited by high rates of re-infection and there are concerns about the possible emergence of drug resistance[6,7]
Populations of interest for controlled human infection (CHI)-S will include Ugandans not previously exposed to schistosomiasis as well as those from schistosomiasis-endemic communities: experience in Kenya with the controlled human malaria infection (CHMI) model showed that participants coming from areas with no active transmission (Nairobi residents) had low baseline responses to malaria, and a challenge response similar to Europeans[3], whereas those resident where active malaria transmission occurs had higher baseline responses - indicative of either recent or prior malaria exposure - and a distinct profile of response to challenge (Kapulu, Bejon personal communication)
Summary
Effective vaccines have proven extremely useful in the prevention of infectious diseases, but are still lacking for major poverty-related and neglected infections, including helminth infections. Populations of interest for CHI-S will include Ugandans not previously exposed to schistosomiasis (perhaps from an urban setting) as well as those from schistosomiasis-endemic communities (prior exposure for inclusion or exclusion can be determined by measuring IgG antibody to schistosome egg antigen): experience in Kenya with the controlled human malaria infection (CHMI) model showed that participants coming from areas with no active transmission (Nairobi residents) had low baseline responses to malaria, and a challenge response similar to Europeans[3], whereas those resident where active malaria transmission occurs had higher baseline responses - indicative of either recent or prior malaria exposure - and a distinct profile of response to challenge (Kapulu, Bejon personal communication). At the stakeholders’ meeting, it was recommended that the principles articulated by the World Health Organisation (2016)[33] and benchmarks developed at the Malawi meeting on Controlled Human Infection Models in Low Income Countries[8] be employed to govern the ethical and regulatory approval process These are set out, which identifies ways in which the Uganda CHI-S will address them. Contributions of social science research to identifying ways of achieving this were desirable
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
