EDCTP portfolio: Malaria

With encouraging progress in malaria vaccine development, the Multi-Stage Malaria Vaccine Consortium (MMVC) will test a novel vaccine combination targeting four stages of the malaria parasite life cycle.

A four-strike vaccine against malaria

The malaria parasite has a complex life cycle, spanning mosquitoes and humans. When injected into the bloodstream following the bite of an infected mosquito, it first invades and multiplies within liver cells, before seeking refuge and multiplying again in red blood cells. When these burst, parasites circulating in the bloodstream can be taken up by a feeding mosquito.

Although only a single cell, the parasite is a master of disguise, adopting entirely different forms at different stages of its life cycle. Malaria vaccine developers typically focus on one specific stage of the life cycle. The only licensed malaria vaccine, RTS,S, targets the initial human stage, to prevent liver infection. However, a vaccine targeting the final bloodstream stage could block transmission to mosquitoes.

The challenge

With exciting progress being made in vaccine development at all stages of the life cycle – pre-liver, liver, red blood cell and bloodstream stages – MMVC has ambitious plans to combine them in a single formulation, maximising the benefits of the individual vaccines.

The four-stage vaccine will include a next-generation version of RTS,S, known as R21; a liver-stage vaccine that has shown positive results in EDCTP-funded trials; a promising vaccine targeting a key protein involved in red blood cell invasion, PfRH5; and a vaccine targeting a key protein in the final bloodstream form, Pfs25.

Results from a series of controlled human infection studies – using new capacity in Africa – and pilot trials will inform the design of an appropriate vaccination strategy. This will be tested in a phase II trial in infants in sites of different levels of malaria transmission. The project will also build capacity to test the vaccine in adults as a possible way of blocking transmission to mosquitoes in malaria elimination campaigns.

The project

The project will generate key evidence on the efficacy of the four-stage vaccine, with the aim of achieving the WHO Roadmap’s target of 75% efficacy. Such a vaccine could make a major contribution to reducing the incidence of an infection that still kills more than 1000 children every day.

Impact


crucial in

widening African

children’s access

to antiretrovirals

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

The malaria parasite has a complex life cycle, spanning mosquitoes and humans. When injected into the bloodstream following the bite of an infected mosquito, it first invades and multiplies within liver cells, before seeking refuge and multiplying again in red blood cells. When these burst, parasites circulating in the bloodstream can be taken up by a feeding mosquito.

Although only a single cell, the parasite is a master of disguise, adopting entirely different forms at different stages of its life cycle. Malaria vaccine developers typically focus on one specific stage of the life cycle. The only licensed malaria vaccine, RTS,S, targets the initial human stage, to prevent liver infection. However, a vaccine targeting the final bloodstream stage could block transmission to mosquitoes.

With exciting progress being made in vaccine development at all stages of the life cycle – pre-liver, liver, red blood cell and bloodstream stages – MMVC has ambitious plans to combine them in a single formulation, maximising the benefits of the individual vaccines.

The four-stage vaccine will include a next-generation version of RTS,S, known as R21; a liver-stage vaccine that has shown positive results in EDCTP-funded trials; a promising vaccine targeting a key protein involved in red blood cell invasion, PfRH5; and a vaccine targeting a key protein in the final bloodstream form, Pfs25.

Results from a series of controlled human infection studies – using new capacity in Africa – and pilot trials will inform the design of an appropriate vaccination strategy. This will be tested in a phase II trial in infants in sites of different levels of malaria transmission. The project will also build capacity to test the vaccine in adults as a possible way of blocking transmission to mosquitoes in malaria elimination campaigns.

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 project will generate key evidence on the efficacy of the four-stage vaccine, with the aim of achieving the WHO Roadmap’s target of 75% efficacy. Such a vaccine could make a major contribution to reducing the incidence of an infection that still kills more than 1000 children every day.

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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