Dr Misaki Wayengera

Uganda

EDCTP portfolio: Career Development Fellowships

Dr Misaki Wayengera will characterise receiver operators of novel EBOV/MARV-GP epitopes using 2014-2015 Ebola patient samples from Sierra Leone.

Rapid diagnostics for early detection of Ebola and Marburg virus at point of care

Ebola and Marburg viruses (EBOV and MARV) form the two generic members of the filoviridae family of viruses. Filoviruses cause rare but highly fatal viral hemorrhagic fevers (VHFs) within rural villages of equatorial Africa. The 2014-2015 Ebola outbreak in West Africa turned into a public health emergency of international concern (PHEIC). Filoviruses are class A pathogens of potential bioterror. There are no easy to use, affordable rapid diagnostic tests for early detection of filoviruses at the point of care (POC) yet.

The challenge

In January 2013, Grand Challenges Canada (through its rising Stars in Global Health scheme) funded Dr Wayengera and his team to test novel conserved epitopes of EBOV/MARV glycoprotein (Gp) as potential diagnostic biomarkers (Grant #S4-0280-01). During the 2014 to 2015 outbreak in West Africa, we transitioned to scale. Over this period, we generated and validated a panel of over 12 mice-derived hybridomas and monoclonal antibodies (MAbs- targeting 4 unique epitopes inclusive of the extracellular domain of EBOV/MARV Gp) for their reactivity with recombinant Gp cloned and expressed within HEK mammalian cells.

The overall goal of this fellowship project is to determine receiver operator characteristics of novel EBOV/MARVGP epitopes using Sierra Leonean patient-samples obtained from the 2014-2015 Ebola outbreak, stored at the National Institute for Communicable Diseases (NICD) Center for Emerging Zoonotic Diseases (CEZD) BSL-IV. Two specific aims are contingent on this goal, i.e to 1) Pre-characterise the patient sample by clinical picture and outcome, ELISA, RT-PCR, and viral culture, and 2) Determine the sensitivity, specificity, positive predictive value, negative predictive value and receiver operator curves of our in vitro pre-validated novel epitopes.

The project

These conserved EBOV/MARV-Gp epitopes and their derivative MAbs are potential biomarkers to mount on a lateral flow immunochromatographic strip-test (LFT) for use at a point of care, e.g. in remote village settings of equatorial Africa, or during a bioterror attack.

The team has initiated testing at the NICDCEZD-BSL-IV in collaboration with LifeAssay Diagnostics but will require more funding to reproduce high-affinity purified MAbs for clinical testing. In addition, the fellow will train 2 Master’s students in Laboratory Practice and Standards.

In August 2019, Dr Wayengera received for his research the first prize in the competition for the WHO Innovation Challenge in the category Product development.

Impact


test the safety and efficacy of this new formulation in young children

Bringing antiretroviral drugs to children

The CHAPAS trials have ensured that many more children with HIV have benefited
from life-saving antiretrovirals.

EDCTP portfolio: HIV & HIV-associated infections

The challenge

Ebola and Marburg viruses (EBOV and MARV) form the two generic members of the filoviridae family of viruses. Filoviruses cause rare but highly fatal viral hemorrhagic fevers (VHFs) within rural villages of equatorial Africa. The 2014-2015 Ebola outbreak in West Africa turned into a public health emergency of international concern (PHEIC). Filoviruses are class A pathogens of potential bioterror. There are no easy to use, affordable rapid diagnostic tests for early detection of filoviruses at the point of care (POC) yet.

In January 2013, Grand Challenges Canada (through its rising Stars in Global Health scheme) funded Dr Wayengera and his team to test novel conserved epitopes of EBOV/MARV glycoprotein (Gp) as potential diagnostic biomarkers (Grant #S4-0280-01). During the 2014 to 2015 outbreak in West Africa, we transitioned to scale. Over this period, we generated and validated a panel of over 12 mice-derived hybridomas and monoclonal antibodies (MAbs- targeting 4 unique epitopes inclusive of the extracellular domain of EBOV/MARV Gp) for their reactivity with recombinant Gp cloned and expressed within HEK mammalian cells.

The overall goal of this fellowship project is to determine receiver operator characteristics of novel EBOV/MARVGP epitopes using Sierra Leonean patient-samples obtained from the 2014-2015 Ebola outbreak, stored at the National Institute for Communicable Diseases (NICD) Center for Emerging Zoonotic Diseases (CEZD) BSL-IV. Two specific aims are contingent on this goal, i.e to 1) Pre-characterise the patient sample by clinical picture and outcome, ELISA, RT-PCR, and viral culture, and 2) Determine the sensitivity, specificity, positive predictive value, negative predictive value and receiver operator curves of our in vitro pre-validated novel epitopes.

The project

The later CHAPAS-3 trial compared the efficacy and safety of three fixed-dose combinations including two without stavudine (found to have some long-term side effects in adults, leading to a recommendation that its use be discontinued in children). The trial the first of its kind in Africa studied nearly 500 children at four sites in two African countries.

These conserved EBOV/MARV-Gp epitopes and their derivative MAbs are potential biomarkers to mount on a lateral flow immunochromatographic strip-test (LFT) for use at a point of care, e.g. in remote village settings of equatorial Africa, or during a bioterror attack.

The team has initiated testing at the NICDCEZD-BSL-IV in collaboration with LifeAssay Diagnostics but will require more funding to reproduce high-affinity purified MAbs for clinical testing. In addition, the fellow will train 2 Master’s students in Laboratory Practice and Standards.

In August 2019, Dr Wayengera received for his research the first prize in the competition for the WHO Innovation Challenge in the category Product development.

ratios forfixed-dose combinations and on appropriatedosage according to weight. 

The CHAPAS-3 trial confirmed the effectiveness of fixed-dose combinations, providing further impetus to the rollout of antiretrovirals to children. Its evidence on abacavir informed the WHO recommendation of abacavir-containing combinations for first-line therapy in children. Trial data have also been used to support applications for regulatory approval for new scored efavirenz tablets.

Impact

L’homme RF et al. Nevirapine, stavudine and lamivudine pharmacokinetics in African children on paediatric fixed-dose combination tablets. AIDS. 2008;22(5):557–65.

Mulenga V et al. Abacavir, zidovudine, or stavudine as paediatric tablets for African HIVinfected children (CHAPAS-3): an open-label, parallel-group, randomised controlled trial. Lancet Infect Dis. 2016;16(2):169–79.

WHO. Guidelines on the use of antiretroviral drugs for treating and preventing HIV infection: recommendations for a public health approach. 2010.

WHO. Consolidated guidelines on the use of antiretroviral drugs
for treating and preventing

HIV infection: Recommendations for a public health approach
(second edition). 2016

Projects: Children with HIV in Africa Pharmacokinetics and Adherence of Simple Antiretroviral Regimens (CHAPAS): CHAPAS-1 and -3

Project lead: Professor Chifumbe Chintu, University Teaching Hospital, Zambia (CHAPAS-1); Dr Veronica Mulenga, University Teaching Hospital, Zambia (CHAPAS-3)

Target population(s): Children with HIV

Sample size: 71 (CHAPAS-1); 480 (CHAPAS-3)

Countries involved: Ireland, the Netherlands, the UK, the USA, Zambia (CHAPAS-1); Uganda, Zambia (CHAPAS-3)

Project duration: 2005–2009 (CHAPAS-1); 2010 –2011 (CHAPAS-3)

EDCTP funding: €1.2M (CHAPAS-1); €4.6M (CHAPAS-3)

Total project funding: €1.2M (CHAPAS-1); €5.0M

About us

The European & Developing Countries Clinical Trials Partnership (EDCTP) is a public–public partnership between 14 European and 16 African countries, supported by the European Union. EDCTP’s vision is to reduce the individual, social and economic burden of poverty-related infectious diseases by affecting sub-Saharan Africa. EDCTP’s mission is to accelerate the development of new or improved medicinal products for the identification, treatment and prevention of infectious diseases, including emerging and re-emerging diseases, through pre- and postregistration clinical studies, with emphasis on phase II and III clinical trials. Our approach integrates conduct of research with development of African clinical research capacity and networking. The second EDCTP programme is implemented by the EDCTP Association supported under Horizon 2020, the European Union’s Framework Programme for Research and Innovation.

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