Publications

Funding for clinical research |drugs, vaccines, microbicides, diagnostics | HIV/AIDS, tuberculosis, malaria, other infectious diseases |sub-Saharan Africa

Dr Moustapha Mbow

Senegal

EDCTP portfolio: Career Development Fellowships

Dr Moustapha Mbow aims to identify geographical footprints (rural to urban gradient) of the immune system for improving vaccine development.

Environmental impact on immune responses relevant to vaccine development

Critical to vaccine efficacy is the induction of a strong and long-lasting immune response. The vaccine development pipeline needs to involve testing in African populations because of differences not only in the genetic background but importantly because of their very diverse environmental exposures, including chronic infections. Recent indications are that geographical differences may define immunological footprints. The challenge is to evaluate the impact of these difference as an integral part of vaccine development.

The challenge

In studies comparing immune responses of rural and urban Africans as well as matched Europeans, Dr Mbow has shown that there are major differences in the immune response that cannot be accounted for by genetic variation alone. These findings so far form the basis of Dr Mbow proposal to investigate the role of environmental differences in immune responses relevant for vaccine development. This study also serves to strengthen research skills in West Africa to conduct in-depth immunological, molecular and bioinformatics analysis for vaccine responses.

At the Immunology Department of the Laboratory of Bacteriology and Virology of Cheikh Anta Diop University Hospital of Dakar, Senegal, a platform of resources is being used to conduct immunological investigations for various studies, including vaccine trials. The Parasitology Department of the Leiden University Medical Centre (LUMC), with which we are collaborating, has developed a mass cytometry (CyTOF®) panel able to analyse over 36 immune markers simultaneously and possesses Illumina technology for analysis of gene transcriptional signatures of immune cells. In addition to methods of characterisation of cell subsets and immune responses already implemented in Senegal, the candidate will be trained to use CyTOF® and Illumina technologies (including the important step of data analysis) to enable him and his institute to participate in the global effort for vaccine development.

The project

The study will improve understanding of the role of environmental differences as a factor in determining differences in immune response relevant to vaccine development. The study aims also to show the feasibility of technologically demanding laboratory assays in a way that is applicable in field settings. The study topic underlines the need for the research capacity development in West Africa which is part of the study.

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

Critical to vaccine efficacy is the induction of a strong and long-lasting immune response. The vaccine development pipeline needs to involve testing in African populations because of differences not only in the genetic background but importantly because of their very diverse environmental exposures, including chronic infections. Recent indications are that geographical differences may define immunological footprints. The challenge is to evaluate the impact of these difference as an integral part of vaccine development.

In studies comparing immune responses of rural and urban Africans as well as matched Europeans, Dr Mbow has shown that there are major differences in the immune response that cannot be accounted for by genetic variation alone. These findings so far form the basis of Dr Mbow proposal to investigate the role of environmental differences in immune responses relevant for vaccine development. This study also serves to strengthen research skills in West Africa to conduct in-depth immunological, molecular and bioinformatics analysis for vaccine responses.

At the Immunology Department of the Laboratory of Bacteriology and Virology of Cheikh Anta Diop University Hospital of Dakar, Senegal, a platform of resources is being used to conduct immunological investigations for various studies, including vaccine trials. The Parasitology Department of the Leiden University Medical Centre (LUMC), with which we are collaborating, has developed a mass cytometry (CyTOF®) panel able to analyse over 36 immune markers simultaneously and possesses Illumina technology for analysis of gene transcriptional signatures of immune cells. In addition to methods of characterisation of cell subsets and immune responses already implemented in Senegal, the candidate will be trained to use CyTOF® and Illumina technologies (including the important step of data analysis) to enable him and his institute to participate in the global effort for vaccine development.

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.

The study will improve understanding of the role of environmental differences as a factor in determining differences in immune response relevant to vaccine development. The study aims also to show the feasibility of technologically demanding laboratory assays in a way that is applicable in field settings. The study topic underlines the need for the research capacity development in West Africa which is part of the study.

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