Immunological Considerations for Schistosoma Vaccine Development: Transitioning to Endemic Settings.

Despite mass drug administration programmes with praziquantel, the prevalence of schistosomiasis remains high. A vaccine is urgently needed to control transmission of this debilitating disease. As some promising schistosomiasis vaccine candidates are moving through pre-clinical and clinical testing, we review the immunological challenges that these vaccine candidates may encounter in transitioning through the clinical trial phases in endemic settings. Prior exposure of the target population to schistosomes and other infections may impact vaccine response and efficacy and therefore requires considerable attention. Schistosomes are known for their potential to induce T-reg/IL-10 mediated immune suppression in populations which are chronically infected. Moreover, endemicity of schistosomiasis is focal whereby target and trial populations may exhibit several degrees of prior exposure as well as in utero exposure which may increase heterogeneity of vaccine responses. The age dependent distribution of exposure and development of acquired immunity, and general differences in the baseline immunological profile, adds to the complexity of selecting suitable trial populations. Similarly, prior or concurrent infections with other parasitic helminths, viral and bacterial infections, may alter immunological responses. Consequently, treatment of co-infections may benefit the immunogenicity of vaccines and may be considered despite logistical challenges. On the other hand, viral infections leave a life-long immunological imprint on the human host. Screening for serostatus may be needed to facilitate interpretation of vaccine responses. Co-delivery of schistosome vaccines with PZQ is attractive from a perspective of implementation but may complicate the immunogenicity of schistosomiasis vaccines. Several studies have reported PZQ treatment to induce both transient and long-term immuno-modulatory effects as a result of tegument destruction, worm killing and subsequent exposure of worm antigens to the host immune system. These in turn may augment or antagonize vaccine immunogenicity. Understanding the complex immunological interactions between vaccine, co-infections or prior exposure is essential in early stages of clinical development to facilitate phase 3 clinical trial design and implementation policies. Besides well-designed studies in different target populations using schistosome candidate vaccines or other vaccines as models, controlled human infections could also help identify markers of immune protection in populations with different disease and immunological backgrounds

Risk assessment for the implementation of controlled human Schistosoma mansoni infection trials in Uganda.

Schistosomiasis is a parasitic infection highly prevalent in sub-Saharan Africa, and a significant cause of morbidity; it is a priority for vaccine development. A controlled human infection model for Schistosoma mansoni (CHI-S) with potential to accelerate vaccine development has been developed among naïve volunteers in the Netherlands. Because responses both to infections and candidate vaccines are likely to differ between endemic and non-endemic settings, we propose to establish a CHI-S in Uganda where Schistosoma mansoni is endemic. As part of a "road-map" to this goal, we have undertaken a risk assessment. We identified risks related to importing of laboratory vector snails and schistosome strains from the Netherlands to Uganda; exposure to natural infection in endemic settings concurrently with CHI-S studies, and unfamiliarity of the community with the nature, risks and rationale for CHI. Mitigating strategies are proposed. With careful implementation of the latter, we believe that CHI-S can be implemented safely in Uganda. Our reflections are presented here to promote feedback and discussion

Analysis of the MUII-plus mentorship programme: reflections of Fellows’ experiences and lessons for other programmes

Background: The MUII mentorship programme began 11 years ago with a successful group mentorship model. Over the years, the programme has evolved and is presently anchored on the “GROW” approach. This model allows individuals to: set Goals (What I want?); Reflect (Where am I now?); think of Options (What can I do?); What to implement (my actions?). It is intended to help fellows (current, honorary, alumni) herein referred to as mentees achieve their short, medium, and long-term research, career and professional goals. Methods: A mixed methods study combining a cross-sectional survey, one focus group discussion and 11 in-depth key informant interviews were carried out between November 2018 and January 2019 to 1) assess the status of the mentorship programme, 2) perform a strength weakness opportunity and threats (SWOT) analysis, and 3) identify factors relevant for sustainability. Results: An open invitation was made to 52 fellows to participate in the survey, and 23 responded. Among respondents, the largest proportions were male [70% (16/23)], and PhD fellows [35% (8/23)]. The respondents rated the fellowship experience as excellent [65% (15/23)], and most [78% (18/23)] revealed they had benefitted greatly from the programme. The SWOT analysis revealed outstanding strengths of having regular fellows’ meetings for peer support, and availability of international collaborations, linkages and exposure. Opportunities identified included large pool of mentees within MUII-plus and evidence of fellows taking up leadership positions. The biggest threat to the mentorship programme was the busy schedule of mentors. Conclusions: The MUII-plus mentorship programme has strong potential to offer research and career mentorship to its fellows. To promote sustainability of the programme, there is a need for innovative ways to engage mentors; such as digital platforms (e-mentorship) for greater mentor-mentee interactions.</ns3:p

Analysis of the MUII-plus mentorship programme: reflections of Fellows� experiences and lessons for other programmes

Background: The MUII mentorship programme began 11 years ago with a successful group mentorship model. Over the years, the programme has evolved and is presently anchored on the �GROW� approach. This model allows individuals to: set Goals (What I want?); Reflect (Where am I now?); think of Options (What can I do?); What to implement (my actions?). It is intended to help fellows (current, honorary, alumni) herein referred to as mentees achieve their short, medium, and long-term research, career and professional goals. Methods: A mixed methods study combining a cross-sectional survey, one focus group discussion and 11 in-depth key informant interviews were carried out between November 2018 and January 2019 to 1) assess the status of the mentorship programme, 2) perform a strength weakness opportunity and threats (SWOT) analysis, and 3) identify factors relevant for sustainability. Results: An open invitation was made to 52 fellows to participate in the survey, and 23 responded. Among respondents, the largest proportions were male [70% (16/23)], and PhD fellows [35% (8/23)]. The respondents rated the fellowship experience as excellent [65% (15/23)], and most [78% (18/23)] revealed they had benefitted greatly from the programme. The SWOT analysis revealed outstanding strengths of having regular fellows� meetings for peer support, and availability of international collaborations, linkages and exposure. Opportunities identified included large pool of mentees within MUII-plus and evidence of fellows taking up leadership positions. The biggest threat to the mentorship programme was the busy schedule of mentors. Conclusions: The MUII-plus mentorship programme has strong potential to offer research and career mentorship to its fellows. To promote sustainability of the programme, there is a need for innovative ways to engage mentors; such as digital platforms (e-mentorship) for greater mentor-mentee interactions.</ns3:p

Ethical and practical considerations arising from community consultation on implementing controlled human infection studies using Schistosoma mansoni in Uganda

Issues related to controlled human infection studies using Schistosoma mansoni (CHI-S) were explored to ensure the ethical and voluntary participation of potential CHI-S volunteers in an endemic setting in Uganda. We invited volunteers from a fishing community and a tertiary education community to guide the development of informed consent procedures. Consultative group discussions were held to modify educational materials on schistosomiasis, vaccines and the CHI-S model and similar discussions were held with a test group. With both groups, a mock consent process was conducted. Fourteen in-depth key informant interviews and three group discussions were held to explore perceptions towards participating in a CHI-S. Most of the participants had not heard of the CHI-S. Willingness to take part depended on understanding the study procedures and the consenting process. Close social networks were key in deciding to take part. The worry of adverse effects was cited as a possible hindrance to taking part. Volunteer time compensation was unclear for a CHI-S. Potential volunteers in these communities are willing to take part in a CHI-S. Community engagement is needed to build trust and time must be taken to share study procedures and ensure understanding of key messages

Ethical and practical considerations arising from community consultation on implementing controlled human infection studies using Schistosoma mansoni in Uganda.

Issues related to controlled human infection studies using Schistosoma mansoni (CHI-S) were explored to ensure the ethical and voluntary participation of potential CHI-S volunteers in an endemic setting in Uganda. We invited volunteers from a fishing community and a tertiary education community to guide the development of informed consent procedures. Consultative group discussions were held to modify educational materials on schistosomiasis, vaccines and the CHI-S model and similar discussions were held with a test group. With both groups, a mock consent process was conducted. Fourteen in-depth key informant interviews and three group discussions were held to explore perceptions towards participating in a CHI-S. Most of the participants had not heard of the CHI-S. Willingness to take part depended on understanding the study procedures and the consenting process. Close social networks were key in deciding to take part. The worry of adverse effects was cited as a possible hindrance to taking part. Volunteer time compensation was unclear for a CHI-S. Potential volunteers in these communities are willing to take part in a CHI-S. Community engagement is needed to build trust and time must be taken to share study procedures and ensure understanding of key messages

Establishing a controlled hookworm human infection (CHHI) model for Africa: A report from the stakeholders meeting held in Lambaréné, Gabon, November 10-11, 2019.

BACKGROUND: Hookworm is a major contributor to worldwide disease burden with over 230 million people infected. It has been identified as one of the Neglected Tropical Diseases that can be controlled and even eliminated through mass drug administration and other effective interventions. Mathematical models have shown that hookworm can only be eliminated via a vaccine. Controlled Hookworm Human Infection (CHHI) models can facilitate rapid development of vaccines and drugs. METHODS: As a first step towards the establishment of CHHI in Africa, we held a stakeholders meeting in Lamberene, Gabon from 10 to 11 November 2019. RESULTS: Discussions revolved around the roles of the different regulatory institutions concerned; the need to strengthen existing regulatory capacity and the role of legislation; creating Gabon-specific ethical guidelines to govern Controlled Human Infection (CHI) studies; development of a study protocol; consideration of cultural and social peculiarities; the need for regular joint review meetings between interested parties throughout the process of protocol implementation; and participant compensation. Moreover, operational considerations concerning the introduction of CHHI in Gabon include the use of the local strain of hookworm for the challenge infections, capacity building for the local production of challenge material, and the establishment of adequate quality assurance procedures. CONCLUSION: The workshop addressed several of the anticipated hurdles to the successful implementation of CHHI in Gabon. It is our aim that this report will stimulate interest in the implementation of this model in the sub-Saharan African setting