A number of novel candidate TB vaccines have been developed and have to be tested in regulatory clinical studies over the course of the next decade. To produce robust results, efficacy trials will have to be conducted at multiple sites involving patients from different populations. Each participating site would need to possess or develop regulatory-quality capabilities. Therefore, capacity building is an important part of the EDCTP-funded TB vaccine studies.
Epidemiological studies in Kenya
Dr Anja van’t Hoog from the Kenya Medical Research Institute coordinated a project to strengthen the KEMRI research site in Western Kenya. This was done in collaboration with the Centre for Disease Control (KEMRI/CDC) program Kisumu and with organisations from Africa, Europe and USA. The aim was to build capacity for phase II and III TB vaccine trials according to the International Conference on Harmonisation/Good Clinical Practice (ICH/GCP) standards.
Two epidemiological studies with related capacity building were conducted. These established, followed up and retained a neonatal and an adolescent (14-18 year old) cohort in the Karemo division of the Siaya district in Kenya. These observational studies began in June 2007 and included no experimental interventions. The neonatal study estimated the one-year incidence of TB disease as diagnosed by two sputum smears, positive for acid fast bacteria (AFB) and/or positive culture. The adolescent study estimated the optimal way to access an adolescent population in vaccine trials.
The capacity building activities included good clinical practice training of all project staff while 25 of them also followed clinical research ethics training. A state of the art TB laboratory is operational since early 2010 and a clinical facility to enhance the diagnosis of paediatric TB was established in the Siaya District Hospital. The capacity built in relation to the epidemiological studies has enabled the KEMRI/CDC site to participate in a multicentre phase II trial of a new TB vaccine (Aeras402/Crucell AD35) in African infants.
Vaccine trial in Ethiopia
An EDCTP-funded project coordinated by Dr Abraham Aseffa from the Armauer Hansen Research Institute (AHRI) in Ethiopia brought together institutions from Ethiopia, Madagascar and Tanzania into a consortium with European partners from Belgium, Denmark, the Netherlands and the UK. The project was centred on a phase I clinical trial of a new TB vaccine candidate but integrated the actual trial conducted at AHRI with capacity building that included scholarships for academic studies, courses in GCP and Good Clinical Laboratory Practices (GCLP), laboratory upgrading, and investment in equipment.
Significantly, this was the first phase I study of a TB vaccine conducted in Ethiopia as well as the first time the candidate vaccine H1 (Ag85B-ESAT-6 + IC31) was evaluated in Africa. In addition, the AHRI clinical trial laboratory has now been developed and upgraded to meet ICH/GCP standards. The institute is now well prepared to conduct further vaccine trials.
The phase I safety and immunogenicity study was completed in April 2010 and showed promising results. Following the promising results of the phase I study, EDCTP has proceeded to fund a phase II trial of the vaccine. This study, led by Professor Peter Andersen from the Statens Serum Institute (Denmark) and conducted at the South African Tuberculosis Vaccine Initiative (South Africa), is a randomised, double-blind, multicentre trial that evaluates the immunogenicity and safety of two doses of the adjuvanted vaccine and uses two different vaccination schedules in healthy adolescents who tested positive for a tuberculosis skin test.
A new TB vaccine for African infants
The EDCTP-funded multicentre phase II trial of a new TB vaccine in African infants aims to evaluate the immunogenicity and efficacy of the Crucell recombinant Ad35 vaccine in BCG-vaccinated, HIV-uninfected infants. The AERAS 402/Crucell Ad35 study, led by Associate Professor Mark Hatherill from the University of Cape Town in South Africa, has a major capacity development component. The objective is to ensure that three distinct trial sites in sub-Saharan Africa develop the requisite infrastructural capacity to conduct phase IIB and phase III trials of new TB vaccines within the next five years. The sites are the South African Tuberculosis Vaccine Initiative (South Africa), the KEMRI/CDC field research station in Kenya and the Manhiça Health Research Centre in Mozambique.
MVA85A candidate vaccine against TB in HIV-infected adults
Prof. Helen McShane from the University of Oxford, United Kingdom, coordinates the study which is to evaluate whether a new tuberculosis vaccine MVA85A will boost immunity and reduce illness from TB in adults infected with HIV. People infected with HIV are at far greater risk of developing TB disease than HIV-negative people. The candidate vaccine is tested in approximately 1400 adults who are 18-50 years of age.
The capacity building component of the project will ensure that two trial sites will be able to participate in similar clinical trials in the future. The site in Dakar, Senegal is managed by the Laboratory for Bacteriology-Virology of University Hospital Centre Aristide Le Dantec, and the site in Khayelitsha, South Africa, is run by the Institute of Infectious Disease and Molecular Medicine of the University of Cape Town. The Scientific Institute of Public Health (WIV-ISP) in Belgium, which first identified the antigen 85A for possible use in a vaccine candidate, is providing in-kind laboratory services for the study.