index
EDCTP portfolio: Malaria
A four-strike vaccine against 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.
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 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 project
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 multi-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 are informing the design of an appropriate vaccination strategy. This is being tested in a phase II trial in infants in sites with different levels of malaria transmission. The project is also building capacity to test the vaccine in adults as a possible way of blocking transmission to mosquitoes in malaria elimination campaigns.
Impact
The project is generating key evidence on the efficacy of a multi-stage vaccine, with the aim of achieving and exceeding 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.
EDCTP portfolio: HIV & HIV-associated infections
The CHAPAS trials have ensured that many more children with HIV have benefited
from life-saving antiretrovirals.
Bringing antiretroviral drugs to children
“
crucial in
widening African
children’s access
to antiretrovirals
”
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 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
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
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 multi-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 are informing the design of an appropriate vaccination strategy. This is being tested in a phase II trial in infants in sites with different levels of malaria transmission. The project is also building capacity to test the vaccine in adults as a possible way of blocking transmission to mosquitoes in malaria elimination campaigns.
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
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
Impact
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.
The project is generating key evidence on the efficacy of a multi-stage vaccine, with the aim of achieving and exceeding 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.