“
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.

The challenge

The RTS,S/AS01 vaccine shows significant protective efficacy against malaria and is undergoing pilot implementation studies in three African countries. However, it does not provide complete protection and the search continues for vaccines with a higher degree of efficacy.

Globally, recent years have seen significant progress made in the development of candidate malaria vaccines. However a major bottleneck is the clinical evaluation of these new vaccines. In particular, there is a need to efficiently identify the most promising vaccines to increase the chances of success in long and expensive phase III trials.

Controlled human infection model (CHIM) studies have emerged as a hugely valuable approach for rapidly assessing the efficacy of developmental vaccines. In such models, volunteers are deliberately infected with pathogens, under highly controlled situations, and are treated before serious disease develops. Crucially, they enable the efficacy of vaccines to be rapidly tested in relatively small numbers of people who are closely monitored. By testing multiple candidates, researchers can quickly identify the most promising for testing in large-scale field trials.

CHIM platforms for malaria have been introduced into several African countries, so studies can be carried out on populations actually affected by malaria. The MIMVaC-Africa consortium is taking advantage of this new capacity to evaluate multiple new promising malaria vaccine candidates. It has drawn together leading academic researchers involved in vaccine development from Europe and Japan, as well as multiple African centres with extensive experience in vaccine clinical trials and use of the malaria CHIM platform.

The consortium plans to use CHIM platforms to evaluate five vaccine candidates. Three are pre-erythrocytic vaccines – designed to prevent infection progressing to clinically serious disease – and two are blood-stage vaccines; they target a later stage in the malaria parasite life-cycle and, as well as protecting individuals, they interrupt transmission to mosquitoes.

Based on the data collected in the CHIM studies, the consortium will then test one or more candidate vaccines in phase II trials to assess their safety, immunogenicity and protective efficacy in infants and young children – those most at risk of serious infections – in endemic countries.

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 MIMVaC-Africa project will accelerate clinical evaluation of five of the most promising experimental malaria vaccines, identifying which are sufficiently effective to warrant progression to a phase III trial. The consortium will maintain contact with all key regional stakeholders to advise them on progress. The project will also build capacity, by expanding the range of sites able to carry out CHIM studies, strengthening clinical trial infrastructures and transferring the latest laboratory assays to participating African centres.

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