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

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Bringing antiretroviral drugs to children

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

The challenge

Tuberculosis (TB) remains a foremost poverty-related disease with a high rate of mortality despite the global immunisation with the only available vaccine, Bacille Calmette-Guérin (BCG). However, this vaccine only provides some protection against the severe forms of paediatric TB but is not completely protective against the disease in infants or pulmonary TB in adults. There is an urgent challenge to develop an affordable, effective and safe vaccine that can protect against the disease in infants and adults.

Dr Adeagbo aims to develop a strategy for the presentation of the vaccine as a single vial through conjugation and lyophilisation.

An adjuvanted recombinant protein vaccine, developed at the Infectious Disease Research Institute, Seattle, USA, is one of the vaccines that are in clinical development for the prevention of pulmonary TB. The current composition comprises two vials, one containing the antigen and one containing an adjuvant, which is bedside mixed immediately prior to inoculation. The mode of association of the adjuvant to the antigen influences immunogenicity, thus appropriate adjuvant-coupled antigens are expected to be suitable for the development of vaccines that induce humoral and cellular immunity. Moreover, lyophilisation has facilitated the formulation of thermostable pharmaceuticals containing proteins with enhanced shelf life and reduced degradation in the presence of heat stress.

The study will explore the use of chemical conjugation strategies to associate the antigen to the liposome. It will also develop and optimise a lyophilisation process for the formulation of a thermostable single-vial vaccine. Field stability of these formulations will be evaluated in selected health facilities in Nigeria. The physicochemical stability of these formulations will be studied using HPLC, dynamic light scattering, and SDS-PAGE while the bioactivity will be tested by evaluating cytokine stimulation using fresh whole blood from donors in order to determine the most stable and bioactive formulation. The study will also involve an evaluation of the differential response of individuals to the vaccine.

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 findings of this study will render a stability profile of a conjugated or lyophilised single-vial vaccine with enhanced immunogenicity and thermostability, ready for storage outside a cold chain facility, thereby enabling delivery to remote populations. This proposal will also enhance capacity for vaccine research in the African scientific community and build a team of young scientists who will be part of the global search for vaccines for infectious diseases in Africa.

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