Project: Strategies to optimize the Stability and Bio-activity of a Clinical Tuberculosis Vaccine

Acronym ID93-TBVaccine (Reference Number: TMA2017CDF-1860)
Duration 01/10/2018 - 30/09/2021
Project Topic Tuberculosis (TB) remains a foremost poverty-related disease with a high rate of mortality despite the global immunization with the only available vaccine, Bacille Calmette-Guérin (BCG). 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. Hence, there is an urgent need for an affordable, effective and safe newer vaccine that can protect against the disease in infants and adults. An adjuvanted recombinant protein vaccine, developed at the Infectious Disease Research Institute (IDRI), Seattle, USA, is one of the vaccines that are in clinical development for the prevention of pulmonary TB. The current composition comprised of two vials, one containing the antigen and one containing an adjuvant, which is‘ bedside mixed’ immediately prior to immunization. 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 lives and reduced degradation in the presence of heat stress. Hence, this proposal aims at developing a strategy for the presentation of the vaccine as a single vial through conjugation and lyophilisation. To achieve this goal, the study will explore the use of chemical conjugation strategies to associate the antigen to the liposome. It will also develop and optimize a lyophilisation process for the formulation of a thermostable single-vial vaccine. This study will evaluate the field-based stability of these formulations 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 findings of this study will give a stability profile of a conjugated or lyophilized single-vial vaccine with enhanced immunogenicity and thermostability, ready for storage outside a cold chain facility thereby sustaining its delivery to remote populations. Thus, this proposal will enhance capacity for development of conjugated and lyophilized adjuvant vaccines within the African scientific community and build a team of young scientists that will be part of the global search for vaccines for infectious diseases in Africa.
Network EDCTP2
Call Career Development Fellowships 2017

Project partner

Number Name Role Country
1 Obafemi Awolowo University Coordinator Niger