"We cannot win the battle against AIDS if we do not also fight TB. TB is too often a death sentence for people with AIDS."
Nelson Mandela, July 2004
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SATVI investigators awarded new grant to explore how our bodies fight TB
The South African Tuberculosis Vaccine Initiative (SATVI) of the University of Cape Town (UCT) is pleased to announce a new research grant from the Bill & Melinda Gates Foundation. The research project, the third SATVI study to be funded by the Gates Foundation, aims to gain new knowledge about how humans protect themselves against tuberculosis (TB).
TB is an infectious lung disease caused by the bacterium Mycobacterium tuberculosis. About half a million new cases of TB disease occur in South Africa every year. World wide, 1.4 million people die from TB each year. We need new vaccines to prevent people from getting the disease, better tools to identify those who have TB and new drugs to treat those who are sick. Progress toward these interventions requires research to understand how our bodies fight TB. This is the goal of this newly funded project.
Dr Thomas Scriba, Deputy Director of Immunology at SATVI, will lead the project, which is a collaborative effort between SATVI at the University of Cape Town, and investigators at Benaroya Research Institute, La Jolla Institute of Allergy and Immunology, New York University, Seattle Biomedical Research Institute and Stanford University.
Dr Scriba commented, "We are thrilled to be awarded this grant. We have assembled an outstanding team of people to address a very significant question using cutting-edge and the most modern scientific approaches."
Valued at ZAR 33.2 million ($3.7 million), the project aims to discover which components of the TB bacterium are targeted by our body's T cells, which are responsible for orchestrating the many different cells of our immune system to effectively fight against infections. This information about the human immune response will inform how we design better vaccines against TB in the future.
This project complements and builds on two others – led by Prof. Willem Hanekom, Director of SATVI – aimed at identifying ways to predict who may develop TB. The Bill & Melinda Gates Foundation has already contributed more than ZAR90 million ($10.7 million) toward funding of these projects. "This important study provides a unique and exciting opportunity to gain a better understanding of how we protect ourselves against TB," said Prof Hanekom.
Results from Historic Phase IIb Clinical Trial for TB Vaccine Candidate MVA85A, performed at SATVI, Published in The Lancet
Results from a Phase IIb clinical trial, which was competed at the SATVI Clinical Field Site, were published in The Lancet on 4 February 2013. The trial evaluated the safety and efficacy of MVA85A in preventing tuberculosis (TB) in infants. MVA85A is a TB vaccine candidate designed to boost immune responses already primed by the Bacille Calmette-Guérin (BCG) vaccine, the currently licensed and widely used TB vaccine. The results show that:
- MVA85A was generally well tolerated, meeting the study’s primary objective of safety
- MVA85A did not provide statistically-significant protection in preventing TB disease in infants previously vaccinated with BCG
Data show that a single dose of MVA85A is not sufficient to confer statistically significant protection against TB disease or infection in infants who had been vaccinated at birth with BCG. There were 32 cases of TB disease in the infants that received BCG + MVA85A compared with 39 cases of disease among those receiving BCG + placebo. Non-significant vaccine efficacy was measured at 17.3% (95% CI -31.9% to 48.2%) at study completion. The vaccine candidate also did not provide statistically significant protection from infection with Mycobacterium tuberculosis, the bacterium that causes TB, which was a secondary efficacy endpoint.
To read more, click here.
To read the abstract of the paper, click here.
To read a commentary in The Lancet about the study, click here.
Longitudinal Changes in CD4 T Cell Memory Responses Induced by BCG Vaccination of Newborns
New findings from SATVI researchers, published online in The Journal of Infectious Diseases, provide a detailed account of the immune response induced by BCG vaccination of newborn babies. The BCG vaccine, which was developed roughly a century ago, is the most commonly given vaccine globally. However, until now, it was not known how the T cell response to BCG develops during the first year of life.
The results show that the BCG-induced T cell response peaks between 6 and 10 weeks of age. Thereafter this immune response slowly wanes and establishes a memory response.
These findings provide critical information for new vaccination strategies against TB. Such strategies will most likely involve administration of a second, different (or heterologous) TB vaccine a few weeks or months after BCG, to boost or modify the BCG-induced immune response. Our study results suggest that boosting of the BCG-primed T cell response may be best after 14 weeks of age, once an established memory response has developed.
For more detail on the study, click here to access the manuscript abstract.
Postdoctoral Fellowship in Epidemiology
TB vaccine research: New network connects European and African institutions
European and African research organisations are gearing up to improve and strengthen collaboration in tuberculosis (TB) vaccine research. Over ten institutions from both continents will create a network where knowledge on clinical trials will be exchanged, joint activities can be explored and coordinated, and where clinical trials capacity will be improved. This month the network has received a budget of 765,000 euros.
The network is funded by the European and Developing Countries Clinical Trials Partnership (EDCTP) and will be coordinated by the Max Planck Institute for Infection Biology in Germany and TuBerculosis Vaccine Initiative (TBVI) from the Netherlands. The programme ‘Collaboration and integration of tuberculosis vaccine trials in Europe and Africa’ (TBTEA) will bring together researchers to strengthen collaboration between the north and the south and to exchange knowledge and know-how. African post-doc researchers will be trained in collaboration with European institutions that, in turn, will benefit from the experiences gained in endemic countries. This will contribute to an improved and sustainable research infrastructure in African countries where TB is a public health threat and prevent overlap and unnecessary duplication of work. European partners can learn how to make more efficient use of existing trial sites whereas African partners will benefit from the translation of European knowledge. From a scientific point of view, the platform will support current and novel assays to evaluate the immune response to vaccination in a clinical setting. The platform will aid the development of improved and harmonized assays, well-defined correlates of protection and valid biomarkers or surrogate markers to assist and accelerate the clinical evaluation of TB vaccine candidates.
TB, often thought to be a disease of the past, is diagnosed in up to ten million individuals per year. Every year nearly 2 million people die. BCG, the only currently available vaccine, conveys very limited protection. The disease causes great human suffering and serious financial burden and hampers economic growth. New vaccines form a crucial part of the fight to eliminate the disease. In the past 10 years a network of European institutions has developed a portfolio of novel vaccine candidates against TB. A number of candidates are now under evaluation in clinical trials in Africa as well as in Europe.
The project joins the following institutions:
- Max Planck Society for the Advancement of Science, Dept Immunology, Max Planck Institute for Infection Biology, Germany
- TuBerculosis Vaccine Initiative (TBVI), The Netherlands
- University of Oxford, UK
- Statens Serum Institute, Denmark
- University of Zaragoza, Spain
- Institut Pasteur de Lille, France
- University of Cape Town, South Africa
- Stellenbosch University, South Africa
- The Infectious Diseases Institute (IDI) at Makerere University, Uganda
- Armauer Hansen Research Institute (AHRI), Ethiopia
- Espoir Pour La Santé (EPLS), Senegal
Source: http://www.tbvi.eu/news-agenda/news/news-message/tb-vaccine-research-new-network-connects-european-and-african-institutions.html
'Paper of the month' for SATVI research
The paper, Functional Capacity of Mycobacterium Tuberculosis-specific T Cell Responses in Humans is Associated with Mycobacterial Load, may be accessed at http://www.stoptb.org/global/research/fundamental.asp
New Director takes leadership of SATVI
1 July 2011, Cape Town – As from today, Professor Willem Hanekom will take over the Directorship of the South African Tuberculosis Vaccine Initiative (SATVI) of the University of Cape (UCT). This follows the decision by Dr Hassan Mahomed to stand down as co-director of SATVI, a position shared with Prof Hanekom since September 2009.
This change in leadership forms part of an evaluation process currently underway in SATVI, which aims to develop a new vision and strategy designed at continued academic excellence and superb operational efficiency. The process also involves an external evaluation, involving local and international experts, during July 2011.
“We believe this change from co-directorship to a single leader is the first step in restructuring SATVI for operational efficiency,” says Prof. Hanekom, as he takes office on his first day as Director.
“This process will take many months to complete, and will involve wide consultation with current personnel members. Personnel will have the opportunity to express their opinion to current leadership, and to the external evaluators,” he has promised his team.
In the immediate future, Willem, as he is known to his staff, plans to spend much time in Worcester to get to know people, and to learn how SATVI operates at the field site.
“Hassan will remain at SATVI and focus on creating more vaccine trial opportunities, while finishing his PhD,’’ he says. “It is an absolute pleasure to build on the phenomenal job Hassan has done at the field site,” adds Willem.
In a letter to SATVI staff from the UCT’s Faculty of Health Sciences’ leadership, Professor Hanekom and Dr Mahomed were thanked for their outstanding contribution to SATVI’s ongoing success, and wished success for their new directions, pointing out that SATVI is widely regarded as the number 1 clinical TB vaccine trial site in the world, and would remain in this position!
Dose-Finding Study of the Novel Tuberculosis Vaccine, MVA85A, in Healthy BCG-Vaccinated Infants
New findings from SATVI researchers Dr Tom Scriba and Dr Michele Tameris, published in the June 2011 issue of The Journal of Infectious Diseases, highlight another milestone in the development pipeline of the new TB vaccine candidate, MVA85A. The paper, co-authored by SATVI Directors Prof Willem Hanekom and Dr Hassan Mahomed, and Oxford University collaborator and developer of the MVA85A vaccine, Dr Helen McShane, reports the first results on vaccination of infants with a new TB vaccine.
The investigators assessed the safety of the vaccine and characterised the induced immune responses in infants aged 5–12 months from the Worcester community outside Cape Town. All 3 doses of the MVA85A vaccine were well-tolerated, and no vaccine-related serious adverse events were recorded. MVA85A induced potent and durable T cell responses, which scientists think are important in protective immunity to TB. These T cell responses did not differ significantly between different doses.
These promising data support evaluation of the efficacy study of this vaccine. A Phase llb trial of 2,784 infants is already underway at SATVI {link to section on Phase IIb}.
Dose-Finding Study of the Novel Tuberculosis Vaccine, MVA85A, in Healthy BCG-Vaccinated Infants.
Scriba TJ, Tameris M, Mansoor N, Smit E, van der Merwe L, Mauff K, Hughes EJ, Moyo S, Brittain N, Lawrie A, Mulenga H, de Kock M, Gelderbloem S, Veldsman A, Hatherill M, Geldenhuys H, Hill AV, Hussey GD, Mahomed H, Hanekom WA, McShane H. J Infect Dis. 2011; 203:1832-43.
SATVI - 10 years of TB vaccine research
10 May 2011, Cape Town and Worcester, South Africa - Ten years following its establishment as a small TB vaccine ‘BCG study’ within the University of Cape Town’s (UCT) Faculty of Health Sciences (FHS), the South African Tuberculosis Vaccine Initiative (SATVI) has become a leader and model in TB vaccine clinical research worldwide, having grown into the largest dedicated TB vaccine research group on the African continent.
First under the leadership of founding Director, Professor Gregory Hussey, and from October 2009 under Co-directors Professor Willem Hanekom and Dr Hassan Mahomed, SATVI’s research has contributed significantly to the development of new TB vaccines, and has improved scientific understanding of the body’s immune response to TB. Since 2006, its research has been published in over 70 articles in high-impact international journals, and its results presented at international conferences and meetings. Further testament to the calibre of its world-reknowned researchers is its representation on several high-level international TB vaccine research committees.
“SATVI has grown from a small operation to a sophisticated world class TB vaccine clinical research facility, with state of the art laboratory facilities at the faculty’s Institute of Infectious Disease and Molecular Medicine (IIDMM) in Cape Town and its research site in Worcester,’ says Professor Hussey, who is now Deputy Dean of Research at the FHS, and whose visionary leadership is credited with steering SATVI’s growth. Worcester, in the Boland region 110 km north east of Cape Town, was chosen for this research, ‘because it has one of the highest rates of TB disease in the world,’ he adds.
Prof Hanekom, who heads the clinical immunology research group within SATVI and is responsible for having established SATVI’s world-class laboratory and biobank facilities, adds that SATVI focuses on a range of areas critical areas in TB vaccine research ‘from new ways to test potential vaccines and how safe they are, to assessing whether the vaccines will work and how our genetic make-up will determine vaccine success’.
Dr Mahomed heads the large SATVI clinical trials team, and has overseen several epidemiological studies and trials involving over 20 000 participants from the Boland. In the process SATVI has developed the infrastructure and capacity to conduct large-scale TB vaccine trials.
“We have tested 4 new TB vaccine candidates at our site. One of these candidates is undergoing efficacy evaluation in the most advanced trial in infants worldwide. SATVI will soon add 3 more TB vaccine candidates to its portfolio of trials,” says Dr Mahomed, adding that SATVI is the only group globally that is testing multiple TB vaccine candidates simultaneously.
Funding
“Our research would not have been possible without the substantial support and funding we receive, especially from our long-standing partner, Aeras, and the Bill & Melinda Gates Foundation who have both been major funders of SATVI’s research since its inception,” proffers SATVI Co-Director, Prof Willem Hanekom, who heads the clinical immunology research group within SATVI. In its 10 years, SATVI has generated millions of dollars in grant income to UCT, illustrating growing global interest and acknowledgement of its groundbreaking research. A significant number of SATVI’s projects are funded through investigator-driven grants, including from the highly competitive National Institutes of Health (NIH), the Wellcome Trust and the European Developing Countries Clinical Trials Partnership (EDCTP).
Partnerships
SATVI has firm relationships with its many global partners. Its involvement in TBVACSIN, an initiative to develop TB vaccine clinical trials capacity in developing countries is important for ensuring that TB vaccines are tested in areas of highest burden.
Above all, community participation and support have been critical to SATVI’s research over the past 10 years. Its Community Advisory Board has served as a voice for the local community in its research.
Social Responsiveness
Over the past 10 years SATVI has had a strong social commitment to the Boland community, particularly the regional health department, providing support for TB training of health professionals and infrastructe development at the regional hospital, and through donating equipment to health facilities and schools where it has conducted its studies. SATVI has also become involved in a number of collaborative outreach activities to raise TB awareness in this community.
SATVI team
Initially comprising of no more than 10 staff, SATVI now has a highly specialised research team of over 170, most of whom are based in the Boland.
Both Co-directors believe that the calibre of SATVI’s team has been instrumental to its success, especially in surpassing the challenges of research in a developing country setting – its’ academic programme aims to build the TB vaccine research capacity of Masters, PhD and Doctoral students, especially from within the African continent.
“And our investment in our young researchers has borne fruit - one of our protégés, Dr Thomas Scriba, recently earned first-runner up for a prestigious international award recognising young scientists from developing countries for outstanding achievement in TB- related research,” says Professor Hanekom proudly, who himself was recently inaugurated as Professor.
Aside from its academic programme, SATVI’s technical, nursing, administrative and support staff receive regular training in Good Clinical Practice (GCP). Developed by SATVI, this internationally reknowned course was recently accredited and is now offered to external organisations.
Sisters Lilly Denation and Linda van der Merwe, two of SATVI’s pioneering team based in Worcester, attribute the team’s success to the passion of the SATVI leadership which they believe has filtered down to all levels of staff - as they’ve seen how SATVI has grown each year.
“From the outset”, they say, “we knew we were part of something amazing, something big, with a vision to build a research site capable of conducting large-scale TB vaccine trials - and this is where we are now!”
Inaugural lecture of SATVI's Prof Hanekom
Wednesday, 5 May, 2011, Cape Town, South Africa - The inauguration of Prof Willem Hanekom at the University of Cape Town’s Faculty of Health Sciences was a highlight not only for this internationally acclaimed TB vaccine researcher. His peers, family and colleagues joined him in celebrating this milestone at a well-attended, moving function presided over by Deputy Vice-Chancellor Prof Crain Soudien.
Prof Hanekom’s inauguration is the fruit of his many years’ dedication to TB vaccine research at the South African Tuberculosis Vaccine Initiative (SATVI), where he is also co-director. He is credited for building the clinical immunology research group within SATVI, including the establishment of world-class laboratory and biobank facilities.
Prof Hanekom’s studies at SATVI, which is located within the Institute of Infectious Disease and Molecular Medicine (IIDMM), have made a significant contribution to a better understanding of the body’s immune response to TB, and to the development of new TB vaccines. His inaugural presentation, entitled ‘Vaccines to stop TB’, highlighted the complexity of challenges faced in TB vaccine research. It was clear that his work has contributed to the field through the development of tools for diagnosing and testing TB, and understanding the body’s immune response.
Introducing him in a touching and often humorous tribute, Dean of the Faculty of Health Sciences, Professor Marion Jacobs, praised his achievements and commended him for his passion and dedication to TB vaccine research in South Africa, describing him as a scientist with a clear vision and being well-respected amongst peers, colleagues and his team.
Director of the IIDMM, Prof Valerie Mizrahi, praised Prof Hanekom as a strong advocate for both TB vaccine research funding and developing capacity amongst a younger generation of researchers. She spoke of Prof Hanekom’s reputation for excellence, citing his extraordinary achievement in being awarded two NIH grants simultaneously, a rare feat for any researcher worldwide.
Prof Hanekom has published widely in high impact journals, is President of the Federation of African Immunological Societies, serves on several international committees, and is a reviewer for multiple journals. He is also the Deputy-Director of the Clinical Infectious Diseases Research Initiative (CIDRI), in the IIDMM.
Other sources:
Extract of speech (620kb mp3 file)
Full audio speech (17.9Mb mp3 file)
