The joint developers and suppliers aim to test safety and efficacy in adults with TB and HIV, in a gold mining centre, reports Miner’s Choice.
Dutch biopharmaceuticals company Crucell NV and Aeras Global TB Vaccine Foundation are conducting the Phase II clinical trial. Aeras-sponsored TB vaccine candidates will be tested for safety in people living with HIV.
Among people living with HIV in Africa and Asia, TB is a leading cause of death. People with HIV living in countries with high TB prevalence are 20 times more likely to develop TB than those who are HIV negative.
According to the World Health Organisation (WHO) 2009 TB surveillance report, one in four TB deaths globally is HIV related, twice as many as previously recognised. In 2007, there were an estimated 1.4-million new cases of TB among people living with HIV and 456 000 deaths. Some 71% of people with TB in SA are co-infected with HIV.
Dr Jaap Goudsmit, Crucell’s chief scientific officer, said there were many potential uses of the new TB vaccine, and it was crucial to test the safety and immune responses in those who have been infected with HIV. “We aim to reduce the global burden of this fatal disease.”
Enrollment of study volunteers for the first stage of the Phase II trial has started. In October 2008, the first Phase II study in adults who have had active TB started in South Africa. AERAS-402 has demonstrated an acceptable safety profile.
Preliminary data indicate that the candidate vaccine induces CD8-cell immune responses in patients who have completed TB treatment.
Seven Phase I studies have been conducted in populations including healthy adults and infants and adult tuberculosis patients;
* A trial in healthy adults not previously immunised with Bacille Calmette-Guerin (BCG), the traditional TB vaccine, demonstrated that the candidate vaccine had an acceptable safety profile in this population.
* A South African study showed CD8 T cell immune responses that are much higher than those seen in humans in any previous TB vaccine study.
* USA studies in healthy adults, focusing on the immunogenicity and safety of two boost doses after BCG priming, showed that two injections of the candidate vaccine are immunogenic, with an acceptable safety profile, when used in combination with a BCG prime, regardless of the boosting interval. This immune response is greater than that detected in the absence of BCG prime, supporting the possible utility of AERAS-402/Crucell Ad35 as a booster vaccine. BCG prime alone shows limited efficacy.
* Testing of the candidate vaccine’s safety in BCG-vaccinated adults with or without latent TB has been completed in Kenya, with ongoing analysis. The vaccine had an acceptable safety profile in this study.
* A trial in South Africa is testing the safety of the candidate vaccine in infants previously vaccinated with BCG vaccine. The study is fully enrolled and dosing is ongoing. To date, the vaccine appears to have an acceptable safety profile in this study.
* A USA trial has started for more detailed analysis of the immune response to AERAS-402/Crucell Ad35, using a known immunogenic regimen of BCG and the candidate vaccine in healthy adults, followed by collection of large numbers of immune cells.
TB is deadly
Tuberculosis is the world’s second deadliest infectious disease, with nearly 9.3-million new cases diagnosed in 2007. According to the WHO, an estimated 1.8-m people died from TB in 2007.
A third of world population has been infected with the TB bacillus and current treatment takes 6-9 months.
The current TB vaccine, Bacille Calmette-Guerin (BCG), developed over 85 years ago, reduces the risk of severe forms of TB in early childhood but is not very effective in preventing pulmonary TB in adolescents and adults, the populations with the highest rates of TB disease.
TB is changing and evolving, making new vaccines more crucial for controlling the pandemic.
Tuberculosis is now the leading cause of death for people living with HIV/AIDS, particularly in Africa. Multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) are hampering treatment and control efforts.
Sources; WHO. Crucell NV. Miner’s Choice.