SAAVI brochure

Developing an affordable, effective and locally relevant HIV/AIDS vaccine for southern Africa

Millions of dollars versus millions of lives
HIV/ AIDS vaccine development does not come cheap – it requires massive investment both in human resources and money. But it’s an investment with a massive payoff – dollars in return for human lives – those of our children and future generations. Of the estimated 50 million people already infected with HIV/ AIDS – nearly 30 million are in sub- Saharan Africa. So, it is our problem and one for which we need an effective preventive solution and we need it as soon as possible. Throughout history developing vaccines has taken time, but vaccination has proven to be the best hope for facilitating the long- term control and eradication of infectious diseases. Historically, however, vaccines produced in developed countries do not become available in poorer countries for many years – a delay that will cost far too many lives in the case of HIV/ AIDS and one which we cannot allow to occur.

SAAVI's vission
SAAVI was created as a national asset – a South African non- profit entity that aims to challenge the historical models applied to biotechnology development. SAAVI is a large- scale scientific, clinical and community endeavour, encompassing comprehensive integrated R& D processes that combine cutting- edge biotechnology with a commitment to true and extensive community involvement. The SAAVI vision is to offer leadership on the African continent in the multitude of HIV/ AIDS vaccine- related research matters and to build capacity for large- scale vaccine trials.

SAAVI is investing in the people of South Africa through preparing communities for research; building human and infrastructural capacity; ensuring the ethical conduct of all aspects of consortium activities; and, ensuring the collection and management of the highest quality data.

SAAVI's scientific agenda is to develop novel biotechnology platforms for candidate HIV vaccines and to move them speedily through the laboratory testing phase, to manufacture, and into human clinical trials. Integrating these product development programmes with solid immunological assessments of the highest quality is critically important.

With six novel technology platforms in development within the SAAVI- funded laboratories in South Africa, SAAVI is currently the only developing country HIV/ AIDS vaccine initiative developing its own candidate vaccines in the laboratories within the country.

SAAVI contributes to international scientific knowledge through its focus on the development of subtype C HIV- 1 vaccines. Subtype C is the genetic strain of HIV most prevalent in southern African, and accounts for the majority of new global infections. Almost all candidate HIV vaccines that have been tested in clinical trials to date have been developed for subtype B HIV and it is not known yet whether vaccines developed using genes from one subtype of HIV will protect against another subtype – much more research and testing over the next decade or more is required to answer this question.

The largest biotechnology R & D programme in Africa
SAAVI involves nearly 200 researchers, clinicians, ethicists, human rights lawyers, information and communications specialists, community educators, contract attorneys, business managers, advisors, etc. and is the largest product- orientated biotechnology research and development programme in Africa. It aims to succeed, along with its global partners, in ridding the world of AIDS. SAAVI is autonomous, but sees close contact and collaboration with international partners as critical to its success. Developing an effective HIV/ AIDS vaccine is a team effort.

Funding
SAAVI's activities are a multimillion- dollar concern requiring significant long- term funding. It is funded as a PPP by many institutions, including the South African government, through the Department of Health and the Department of Science and Technology, and private sector partner, Eskom. In addition, SAAVI receives funding and support from international organisations such as the US National Institutes of Health ( NIH), the European Union ( EU), and the HIV Vaccine Trials Network ( HVTN).

A significant proportion of the funding to date has been spent on creating a series of biotechnology platforms to develop novel candidate vaccines. This investment has now been successfully realised, as candidate HIV vaccines are emerging for manufacture and human clinical trials. An important component of this capacity developed has also been in the area of immunology, where the ability to monitor immune responses to HIV vaccines ( in humans and animals) has been developed. Over time, significant funding will move into financing clinical trials of promising candidates and into community preparation for large-scale efficacy trials.

Funding requirements will dramatically increase over the clinical trial testing process. Currently phase I and II trials can be undertaken with the investment of perhaps a few million US dollars. By contrast, a properly constructed phase III trial that will stand up to stringent regulatory scrutiny is estimated to cost approximately US$ 30 million.

Ever- increasing financial resources will also be required for investment in ethical protocol development, patenting, protection of intellectual property, and, preparation for vaccine manufacture. Other areas that will require substantial future funding include:

• Adolescents – research into the ethical and legal issues regarding research on adolescents is being performed. Adolescents will be the age group that will most need to be vaccinated against HIV/ AIDS. It will therefore be necessary to include adolescents in clinical trials at some point in the process of testing vaccines to ascertain if the test vaccines elicit a different response in an adolescent immune system. An immense mobilising of programmatic activity will be required to prepare the path forward for this.
• Patenting – great care will continue to be taken to ensure that various candidate vaccines and novel technology approaches developed by SAAVI are protected by appropriate patents, so as to ensure that we can exploit the technology in our own environment, while also providing others with the same technologies to exploit further in their environments.
• Manufacturing and manufacturing capacity – extensive funding will be required for the manufacturing of vaccines in future. It is estimated currently that a suitable manufacturing plant for HIV/ AIDS vaccines may cost as much as R3 to 4 billion. In the interim ( before an effective vaccine is found), extensive investment in people and biological processes is required to build capacity in the sophisticated manufacturing processes for HIV/ AIDS vaccines.
• Standards of care – appropriate mechanisms are needed to ensure that the future care needs of trial participants who become infected during the course of a vaccine trial are covered financially. Appropriate care packages will need to be devised and funded in cases where SAAVI is the trial sponsor testing novel vaccines developed by South African scientists for South Africans.
• Clinical trials – the clinical trials will be extremely expensive – particularly phase III efficacy trials involving thousands of volunteers who need to be followed up over a three- to fouryear period with ongoing monitoring and blood testing. It’s currently estimated that a phase III trial will cost at least US $ 30 million.
• Trial site preparation – building the infrastructure for trial sites that meet international standards and will pass the stringent international review procedures and inspections required for clinical testing is an extremely expensive endeavour.
• Community preparation – by the time we are ready to commence phase III trials we will need well- informed and educated communities which are able to make decisions about their participation both as communities and as individuals. This will require extensive and ongoing preparatory work in all sectors and long- term progressive expansion into community and social structures.
• International relations and collaborations – unprecedented levels of international scientific collaboration will be required to develop a successful vaccine against HIV/ AIDS in the shortest possible time. This means funding is needed for travel, training, capacity development in new scientific techniques, and investment in international lobbying and fundraising activities at the highest levels.
• Data management – huge quantities of data will be generated by the trials which will have to be stored, managed, accessible and reproducible for future trials. This will require investment in suitable, highly sophisticated data management systems and in appropriately qualified and trained personnel.
• Greater communications and lobbying – there is an urgent and ongoing need to expand our lobbying and communications- related activities. This will require increased staffing capacity, as well as funding for training initiatives and advertising in different media with the goal of facilitating recruitment and creating an environment conducive to conducting clinical trials. Extensive lobbying activities will be required with the political, business and media sectors, among others.

SAAVI consortium partnerships
SAAVI is a broad- based community research initiative that supports programmes at various South African academic institutions, which focus on specific areas. There are many areas, with our core functions including:

• Teams at the National Institute for Communicable Diseases ( NICD) and other laboratories, examining complex immune responses to HIV vaccines.
• Two large laboratory research teams at the Universities of Cape Town and Stellenbosch dedicated to the development of novel HIV vaccines.
• These two laboratory groups are centrally involved with the characterisation of many local isolates of HIV to ensure that our vaccines are well matched to local strains of HIV in South African populations.
• The HIV/ AIDS Vaccines Ethics Group ( HAVEG) at the University of Natal is responsible for researching and developing ethical guidelines that are locally relevant and facilitate ethically sound vaccine trials.
• Multiple trial site clinical teams. These include: a) the HIV vaccine division of the Perinatal HIV/ AIDS Research Unit at the Chris Hani Baragwanath Hospital in Soweto; b) the HIV Vaccine Research Unit at the Medical Research Council in Durban; c) the Cape Town HIV Vaccine Clinical Trials Consortium with funding channelled through the Desmond Tutu HIV Foundation; and, d) Aurum Health Research, a subsidiary of Anglo American, that will develop trial sites in the North West Province. Additional trial sites will be developed as the need arises.
• SAAVI also has an extensive community preparedness programme – a consortium focusing on community education; legal and human rights; education; and, media and communications.
• A behavioural science research project that will investigate many complex behavioural aspects including the reasons why people volunteer for clinical trials, why they wouldn't and why they might decide to leave a clinical trial, is also being developed by research teams attached to the trial sites.
• The Centre for Actuarial Research at the University of Cape Town will be involved in undertaking the actuarial assessments of future vaccine production and supply needs.

International collaboration
SAAVI is a highly integrated part of the worldwide drive by global organisations to develop an HIV/ AIDS vaccine, and enjoys close collaboration with many other global players in the field, including organisations such as the US National Institutes of Health ( NIH), the NIH- funded HIV Vaccine Trials Network ( HVTN), the International AIDS Vaccine Initiative ( IAVI), the European Union ( EU), the African AIDS Vaccine Programme ( AAVP), the European Developing Country Trial Platform ( EDCTP), the Ethiopian AIDS Vaccine Initiative ( EAVI), the Nigerian AIDS Vaccine Programme ( NAVP) and the Botswana Harvard AIDS Institute, as well as international companies such as Cobra, Therion, Merck, Chiron, Large Scale Biology Corporation and Microscience.

International collaboration is essential in order to fast track the development of an HIV/ AIDS vaccine both for South Africa and the rest of the world, and SAAVI values these collaborative ventures. Although closely collaborating with these and other organisations, SAAVI operates independently allowing it to pursue its own specific goals and maintain its focus on the needs of the southern African region.

Highlights in local vaccine efforts
SAAVI continues to make substantial progress in the field:

• The first candidate HIV vaccine to be given approval for a phase I clinical trial was for the Venezuelan Equine Encephalitis ( VEE) vaccine. Prof. Carolyn Williamson ( SAAVI investigator, University of Cape Town), and Robert Johnson ( University of North Carolina), were awarded the 2001 World Technology Forum Award for their work on this subtype C vaccine. This candidate vaccine received approval to enter phase I trials in South Africa and the USA during 2003, making it the first subtype C vaccine to enter clinical trials in the world.
• Other trials from different sponsors are planned and expected to proceed during 2003 and 2004.
• Increased support from the primary funders: a) the Department of Health doubled its funding of SAAVI from R5 to R10 million per annum; b) the Department of Science and Technology has continued to commit R10 million per annum to SAAVI; and, c) Eskom increased its funding to SAAVI from the original R7,5 million to R15 million per annum and agreed to fund the initiative for the next five years – making this the largest- ever corporate contribution to HIV/ AIDS vaccine research and development in the world. Continuation of a grant from the US NIH HIV Vaccines Trial Network ( HVTN) to prepare clinical trial sites.
• Expanded funding from the EU for vaccine preparedness and community education initiatives.
• The accreditation of the SAAVI group at the National Institute for Communicable Diseases as the only laboratory outside the US that is mandated to perform HVTN- related clinical trial immunological studies and testing.
• Active collaborative projects with foreign institutions and companies have allowed SAAVI to increase the number of candidate vaccines in development. There are now six internal possible novel candidate vaccines under evaluation by researchers at the Universities of Cape Town and Stellenbosch. There are also many collaborative projects making use of SAAVI genes.
• SAAVI continues to manufacture HIV/ AIDS vaccines and perform toxicity testing using support awarded by the NIH. These trials with SAAVI products could begin as early as the fourth quarter of 2004.
• SAAVI investigators continue to be extensively involved in the African AIDS Vaccine Programme, which was launched in the Cape during 2002.
• The HIV/ AIDS Vaccines Ethics Group ( HAVEG) was chosen by the chair of the South African MRC Ethics Committee to co- ordinate the development of national ethical guidelines for HIV/ AIDS vaccine trials in South Africa. These guidelines have been accepted by the National Health Research Ethics Committee. HAVEG also co- ordinates the Ethics, Law, Human & Legal Rights Working Group of the African AIDS Vaccine Programme ( AAVP).
• The testing protocols of the Life Offices’ Association were adapted to make provision for trial participants who may require more sophisticated HIV testing when applying for insurance.
• Relationships were concluded with and formal endorsement was obtained from organisations such as the Biovac Vaccine Manufacturing Consortium, the National Association of Federated Chambers of Business, the South African Chamber of Business and Metropolitan Life.
• SAAVI investigators are also playing major leadership roles in specialised groups within the different international HIV/ AIDS vaccine structures.

The way forward
SAAVI aims to push promising technologies successfully through the manufacture and clinical trial processes, while also ensuring good attention is paid to the community issues important in creating an enabling environment for these trials. Within the next few years there will be many phase I and II clinical trials running simultaneously – involving both collaborative and SAAVI- developed products. SAAVI looks forward to the collaboration with these partners in the search for an effective HIV/ AIDS vaccine.

Specific attention and priority will also be given to an integrated phase III trial site development programme and the development of human capacity in large clinical trials.

SAAVI phase III preparation
This is a collaborative project involving the four clinical trial sites ( in Soweto, Durban, Cape Town and Orkney), and the combined efforts of the SAAVI- funded personnel at the University of the Western Cape, the South African National Bioinformatics Institute, the Universities of Cape Town, Stellenbosch and Natal, and the MRC.

This programme’s primary goal is to measure the HIV incidence ( the rate of new HIV infections/ HIV seroconversions) in high- risk volunteer communities that would potentially be involved in phase III trials.

It is planned that the programme will follow approximately 750 volunteers per trial site over a two- year period. The preparation programme will involve a complex and integrated analysis of the human and viral factors influencing infection and immunity. It is projected that this will provide a comprehensive guide for future phase III trial strategies.

Despite intensive and ongoing risk- reduction counselling, it is estimated that many people on phase III trials will seroconvert each year. The information that will be gathered will include data on the genetic variability of the community ( through HLA typing); determining the genetic variability of the virus ( through viral genetic analysis); and, measuring and analysing immune system responses in those who become infected during the programme. Assessments will include analysing antibody and cellular immune responses ( measured CD4 and CD8 epitope responses); and, the measurement and monitoring of CD4 count and viral load to establish viral set points – vital information to establish the natural set point and its possible effect on disease progression.

In conclusion
SAAVI is proud to be the continental leader in the development of an affordable, effective and locally relevant HIV/ AIDS vaccine for southern Africa. SAAVI is committed to the worldwide effort of accelerating vaccine development by partnering with international organisations and research teams to end the global HIV/ AIDS plague that continues to devastate nations around the globe.

For more information, please contact us