Project Title: An open label randomised controlled trial of two versus three doses of Rotarix™ vaccine for boosting and longevity of vaccine immune responses in Zambia.
EDCTP Senior Fellow
|EDCTP PhD Student
Natasha Makabilo Laban
|EDCTP MSc student
This is an investigator led study to explore the potential value of a third dose of rotavirus vaccination for improving vaccine responses and longer-term protection for immunized infants.
The study is registered at Pan African Clinical Trials Registry and is available via the link: https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=3096
Enrolment status: Completed 212
Current status: Follow up
Project Title: Immunological Characteristics of a Population at Risk of Cholera Before and After 1st and 2nd Dose of Oral Cholera Vaccine.
|EDCTP PhD Student
|EDCTP MSc student
This study aims to explore host genetic factors, HIV and nutritional status on uptake of Oral Cholera Vaccine (OCV) of a Population at Risk of Cholera in Lukanga Swamp, Zambia.
Enrolment status: Completed 222
Current status: Sample analysis and participant follow up
Project Title: A Phase 1 age descending placebo controlled clinical trial to examine the safety, tolerability, and immunogenicity of an oral inactivated ETEC Vaccine (ETVAX®) with dmLT adjuvant in healthy adults and children in Zambia.
EDCTP Senior Fellow
| PhD Student
Cynthia Phiri Mubanga
| Co-Principle Investigator
Diarrhoea remains one of the major causes of morbidity and death among children below five years of age living in developing counties. The majority of cases of diarrhoea which end in death occur in children below the age of two. Enterotoxigenic Escherichia coli (ETEC) is one of the top four pathogens that causes moderate to severe diarrhoea (MSD) and while strides have been made to develop vaccines for these pathogens there is currently no licensed vaccine for ETEC. ETEC is also associated with other long-term negative health and economic impacts for children (i.e. stunting, poor cognitive development) and their families in low- resource countries. Establishing the protective efficacy of promising ETEC vaccine candidates is a high priority for the World Health Organization and European & Developing Countries Clinical Trial Partnership (EDCTP).
This study seeks to evaluate a vaccine against ETEC diarrhoea called ETVAX®. The objectives are to establish the (i) safety and (ii) immunogenicity of ETVAX® in children aged 6-9 month old and 10-23 month old, respectively in Zambia. Our team aims to move ETVAX®, an inactivated whole cell vaccine candidate, into advanced clinical development including field efficacy testing. This is a Phase 1 age descending study in adults, children 10-23 months and children 6-9 months to establish the safety and immunogenicity of ETVAX® in Zambia.
In addition to the evaluation of the ETVAX vaccine this study will also support two PhD projects. The academic students on this project will contribute to closing global knowledge gaps by addressing the following objectives:
PhD student: Cynthia Mubanga
Study title: Characterization of systemic Memory B and T cell responses to an oral inactivated vaccine against enterotoxigenic e.coli (etvax®) in Zambian children aged 6-23 months.
Study Summary: Enterotoxigenic E. coli (ETEC) is a major cause of diarrhoea in under-five children and in travelers to low- and middle-income countries (LMICs). Vaccination is widely understood to be the most effective mode of prevention of infectious diseases. Therefore, development of an ETEC vaccine is a top priority on the global health agenda. A suitable vaccine against ETEC must not only induce a mucosal IgA response but must also produce an immunological memory response. It must also induce production of cross-reactive antibodies to cover a good number of the ETEC pathotypes.
The ETVAX® vaccine (Scandinavian Biopharma, Sweden) is an inactivated oral vaccine and the most advanced of the ETEC vaccines currently under development, that has shown promising results in trials conducted in Bangladesh and Sweden.
This study will investigate the immunogenicity of ETVAX® vaccination in Zambian children (6-23 months) by examining the memory responses at various time points and correlate them with the number of doses of the vaccine. The functional capacity of vaccine-induced antibodies will also be determined.
PhD Student 2: Suwilanji Silwamba
Study Title: Molecular Epidemiology of Enterotoxigenic Escherichia coli presented by infants under five in Lusaka.
Study Summary: Enterotoxigenic Escherichia (ETEC) is a common cause of diarrhoea in children. ETEC causes disease by adhering to the small intestine epithelium by means of colonisation factors (CFs). Effects of enterotoxins lead to watery diarrhoea symptoms. In developing countries ETEC vaccine development has become an important primary prevention strategy.
Vaccine development is driven in part by specific disease burden data. This effort will contribute to Zambian ETEC data by evaluation of stool samples from children under five affected using a novel diagnostic loop mediated isothermal amplification (LAMP) technology. Whole genome sequencing of ETEC will be used to characterize common CFs and putative virulence factors (VF) in the Lusaka population, which has never been done before and will contribute to background data needed for vaccine evaluation.
Literature suggests that AMR has increased in the last two decades and approximately 30% of clinical isolated ETEC lack a known CF. To investigate this phenomenon in Zambia, this study seeks to identify AMR patterns, novel CFs and VFs by comparative genomics as well as phenotypic analyses.
Co- Principle investigator: Nsofwa Sukwa
Nsofwa Sukwa is an early career researcher who is currently working as a study physician on 2 rotavirus vaccine clinical trials. She is a medical doctor and clinical dietician currently working as a clinical research fellow under the Enteric diseases and Vaccines research unit. The unit has previously focused on two of the top five aetiological agents of childhood diarrhoea namely Rotavirus and Vibrio Cholerae and has now added Enterotoxigenic E coli (ETEC) to their portfolio through this clinical trial.
Clinical trial Registration
The study is registered at Pan African Clinical Trials Registry and is available via the link: https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=7094
Enrolment status: Not yet recruiting
Current status: Approved by UNZABREC
Sponsored by Scandinavian Biopharma
Funded by the European & Developing Countries Clinical Trials Partnership (EDCTP)