TB Vaccine Development: SA Tuberculosis Vaccine Initiative & Aeras Global Tuberculosis Vaccine Foundation briefings

Meeting report

Tuberculosis (TB) Vaccine developments
Chairperson’s opening remarks
The Chairperson welcomed Ms B Ngcobo (ANC) as the new Whip of the Committee, and welcomed the presenters.

South African TB Vaccine Initiative Briefing
Dr Hassan Mohamed, Co-Director, South African Tuberculosis Vaccine Initiative (SATVI), explained the medical implications of tuberculosis (TB) and noted that South Africa had the second highest rate of TB in the world. Within South Africa, the Western Cape had the highest rate of TB, followed by Kwazulu-Natal and the Northern Cape. TB affected all ages, but certain age groups such as infants and young adults were more likely to develop it. TB was very common in persons whose immune systems were weakened. 50% of TB patients were found to be HIV positive.

The treatment of TB was considered cheap and effective, but the emergence of Multi-Drug Resistant (MDR) and Extremely Drug Resistant (XDR) TB was a concern. This could be controlled by acquiring better drugs, by finding better ways of diagnosing the disease, by having optimal health care structures, and by producing better vaccines to prevent all forms of TB. The current TB vaccine was called Bacillus Calmette-Guerin (BCG), and it was very safe, except if given to HIV positive babies. It was also not very effective at preventing lung-TB in young children.

SATVI’s mission was to develop new and effective TB vaccines. It would obtain this goal through high quality basic science, clinical and public health research, within an academic centre of excellence. The initiative’s laboratories and management structures were based in Cape Town, while its clinical site was based in Worcester, as there was a high rate of TB in the Boland area. SATVI was seen as the leading clinical site for testing new TB vaccines in the world. The organisation already enrolled 20 000 people in trials. BCG and four new TB vaccines have already been tested. A new TB vaccine in 80 years was already in the first stage of a trial.

Prof Willem Hanekom, Co-director, SATVI, stated that the Initiative had achieved world recognition for addressing critical questions in TB vaccinology. SATVI also received a R36 million grant from the Gates Foundation and R20 million from the National Institutes of Health (NIH). The organisation worked in partnership with various entities such as the Department of Health (DoH), the Aeras Global TB Vaccine Foundation, the NIH, Crucell, the National Research Foundation (NRF) and the Tuberculosis Vaccine Initiative (TBVI).

He reiterated that it took time to develop a new TB vaccine, as SATVI had to ensure that the vaccine was safe and that it would prevent TB. A new vaccine could be expected between 2016 and 2020. This, however, could not be done without the support of the government and the South African public. All SATVI’s funding came from abroad but he urged that funding support from within South Africa was essential.

Aeras Global TB Vaccine Foundation Briefing
Mr Sebastian Gelderbloem, Head, Aeras Global TB Vaccine Foundation, said that the Foundation’s mission was to develop a new and more effective TB vaccine and to ensure availability of vaccines to all who would need them. This would be done through collaborations with academic, biotech, pharma and Non-Governmental Organisation (NGO) partners. The Foundation (Aeras) wanted to develop a modern replacement for BCG with the addition of booster vaccines. It developed vaccines in its own laboratory and manufacturing plant.

Mr Gelderbloem noted that the existing TB vaccine was ineffective. The World Health Organisation’s (WHO’s) recommendation on BCG was that HIV positive children, regardless of the symptoms, should not be BCG-vaccinated. All high-risk infants needed to be screened for HIV. This was very difficult to implement in many countries. The goal for developing a better TB vaccine was to eliminate TB as a public health threat. The drug had to be safe and effective in preventing TB in children, adolescents and adults, including people with HIV. The vaccine would also have to protect against all forms of TB, including MDR and XDR forms.

Twelve candidates had already been entered into clinical trials. Nine were currently being tested. There was capacity and infrastructure being developed at several sites. Aeras’ approach to the new vaccine would be to improve BCG and make a recombinant “rBCG”. It also wanted to give booster vaccinations to infants and adolescents who had received BCG at birth. Large-scale community-based clinical trials were being conducted in high burden countries. Aeras partnered with local research institutions to establish field sites and conduct clinical research. Aeras was also in partnership with institutions in Uganda, Cambodia, India, Senegal, Kenya, and Mozambique. Aeras was also in partnership with SATVI and AURUM. It developed a field site in Worcester, which was the most advanced site in the world for TB vaccine trials.

Some of the benefits of local clinical research were that it allowed the country to retain local talent and expertise. It also increased awareness about TB in the community, supported and enhanced local clinical research capacity, contributed to community health and education, and allowed for investment into infrastructure to use for clinical trials for other diseases.

Aeras acknowledged the support of major donors such as the Bill and Melinda Gates Foundation, the US Food and Drug Administration (FDA), the National Institute of Allergy and Infectious Diseases, and UK Aid. However, Mr Gelderbloem also acknowledged the need for government support to effectively fight TB.

Discussion
The Chairperson thanked both organisations for the excellent work they were doing. He believed that the research they provided to Members was important as it would help them to make proper decisions regarding TB. He noted that most of the funding for TB came from sources outside of the government. It was the Committee's duty to discuss how it could get the government to fund these organisations. It seemed that government supported the research for many other diseases but seemingly forgot about TB. TB was a disease that could be cured, yet it was still taking many lives in the country. The government had to find a way of preventing TB.

The Chairperson noted that SATVI’s presentation showed that the Western Cape had the highest rate of TB. However, he thought that the Eastern Cape probably had the worst rate of TB, and the only reason this was not shown was because the province was mostly rural, and proper research was not generally conducted in these areas. It was interesting that HIV positive infants were not supposed to be vaccinated. He asked if the antibodies or just the antigens, were tested in infants.

Dr Hassan replied that the Chairperson made a very valid point about the TB rates in other provinces. However, he was not sure why there was such a difference in TB reporting between the Western Cape and other provinces. One of the reasons could be due to the differing level of infrastructure and the level of reporting of cases. The Eastern Cape could possibly have a worse rate of TB than the Western Cape, but if its reporting infrastructure was not in place, the epidemic would seem less visible. The Western Cape had better reporting structure and therefore, seemed to have better rates. He warned that this could be an artificial difference. There were other explanations that could be offered, such as the Western Cape's climate being a little different from other provinces. The Western Cape had very wet winters that forced people indoors into over-crowded conditions, which then facilitated the spread of TB. There was still a lot of information that was unknown that could contribute to the problem.

Dr Mohamed answered that it was very difficult to find out if an infant was HIV positive. If a normal HIV test was given, it would test the mother's antibodies. However, whether or not an infant was HIV positive could only be established when the infant was six weeks old, through a special test. The test detected the evidence of the virus in the infant itself. A decision had to be made whether or not to give the infant BCG at birth, even though it could not be established with certainty at that stage whether the child was HIV positive. This was a challenge with which the government was struggling at the moment. The World Health Organisation (WHO) made a recommendation that countries such as South Africa should address the matter and work out whether the TB vaccination should be deferred until an infant’s HIV status could be ascertained. This had its own implications and challenges, and required its own discussion.

Prof Hanekom clarified that the WHO's recommendation was that HIV/AIDS exposed babies should not receive the TB vaccination until it was known for certain whether the infants were infected with HIV or not. He thought this was an appropriate recommendation, given the evidence that was put on the table. However, this recommendation had not been implemented in any developing country to date. Given South Africa's situation, it was possibly more appropriate to give BCG to any infant that was exposed to HIV at birth. He was aware that this put the infants at risk of developing other diseases caused by BCG, but pointed out that the figures showed that where antiretroviral interventions were made to prevent mother to child transmissions, fewer than 5% of the country's infants were infected with the virus. This was a difficult issue, and since the country did not have optimal public health infrastructure, even more difficult decisions had to be made about what was best for the majority of the infants.

Mr M Waters (DA) asked the organisations to elaborate on their need for government funding. They had mentioned that they had applied to the Medical Research Council (MRC) for funding, but it was such a small amount that it did not compare to other donors’ contributions. He asked if SATVI had ever held meetings with the Minister, as he always spoke about the link between HIV and TB, and how important it was to address both diseases. It seemed strange to him that the Department of Health (DoH) was not on board financially. He enquired whether the DoH was providing the organisation with any other resources, such as staff and equipment, since they were not funding directly. 

The Chairperson recalled a meeting with the MRC, where it was complaining bitterly that it did not have any resources.

Prof Hanekom responded that SATVI had made very small funding applications to local agencies. The applications were mostly for funding for specific students. TB was as big a problem as HIV/AIDS, but only five cents was given toward TB research for every one dollar given for HIV research. This was an incredible disparity. The onus was on SATVI to approach the DoH and the Department of Science and Technology (DST) to negotiate for funding.

Mr Gelderbloem added that neither organisation had met with the Minister, but they had interacted with officials from the DoH. One of their joint goals for 2011 was to meet and interact with the Minister on the issue of TB vaccinations. 

Dr Mohamed commented that the DoH supported the organisations, especially at the local level. They worked closely with the DoH regarding trial work conducted by SATVI. It was important to note that many of the officials and organisations with whom SATVI met did not have direct access to funds but offered support in other ways.

Ms B Ngcobo (ANC) asked if the organisations had worked with the Department of Science and Technology (DST) and the Council for Scientific and Industrial Research (CSIR), who were working on nanotechnology drugs for the treatment of TB. She was aware that Worcester was the worst town affected by TB in the Western Cape. She agreed with the Chairperson that there could be other provinces that were worse off than the Western Cape when it came to the rate of TB.

Ms Ngcobo asked if the organisations worked with any universities situated in rural areas.

Dr Mohamed said that SATVI worked in Worcester. Unfortunately, there was no rural university in that area but SATVI would be open to collaborating with other institutions and universities in other parts of the country. SATVI, along with Aeras, preferred a collaborative approach rather than a competitive approach.

Mr Gelderbloem added that the organisations would be working with institutions in Kwazulu-Natal as well as in other provinces.

Ms Ngcobo further noted that the organisations were receiving international funding and wondered if there were conditions attached to the funding and if they would be able to share a vaccine with other countries, at a fee, if one was ever found.

Prof Hanekom replied that there was an initiative within the DST to look into a TB vaccine. The project was still in an early phase, but he hoped that it would be successful. He said that SATVI would not work with a partner unless there was a policy in place that would allow the vaccine to be made available, worldwide, in a fashion that was sustainable and equitable. He said that Aeras had structures in place for such time as a vaccine may be found and became available to the market. There was a two-tier marketing strategy written into the programme. This looked at different pricing systems for the developing and the developed countries.

Mr Gelderbloem added that Aeras' goal was to develop vaccines that could be made available cost-effectively. Aeras did not want to get into a situation where money could be made from developing countries. Aeras saw TB as a disease that had to be fought and eliminated.

The Chairperson thanked SATVI and Aeras for the work that they were doing. He did not think there were any institutions that would not want to fund the organisations if they knew the work they were doing. South Africa seemed to be leading in TB vaccine research and he wanted it to stay this way. He hoped Aeras and SATVI would meet with the Minister, and asked them to call on the Committee if they experienced any challenges. It was especially important to address the issue of TB along with the spread of HIV. The Committee was hopeful that the spread of TB would decline.

Prof Hanekom said that the Committee was welcome to visit the site in Worcester.

The Chairperson answered that the Committee would consider the offer.

The meeting was adjourned.