Development of an AIDS vaccine: perspective from the South African AIDS Vaccine Initiative
http://www.100md.com
《英国医生杂志》
1 South African AIDS Vaccine Initiative, Medical Research Council, PO Box 19070, Tygerberg 7505, South Africa
Correspondence to: T J Tucker saavi@mrc.ac.za
Most work on HIV vaccines is being done in the public sector rather than the pharmaceutical industry. Although international cooperation is producing candidate vaccines, greater investment is needed to speed up progress
Introduction
The processes of developing a vaccine against HIV have been distinct from that of any previous pharmaceutical product. Although most existing vaccine capacity resides within the private sector, most research into an HIV vaccine has taken place (or been funded from) within the public sector. This is because manufacture and distribution of an HIV vaccine is unlikely to generate much profit.3
HIV is a genetically diverse microbe that is categorised into many genetic subtypes. Although HIV subtype B is responsible for a minority of HIV infections, it is the predominant subtype in developed countries.4 Early vaccine development focused on sub-type B genes and proteins, and clinical trials were predominantly in the United States and Europe. However, in the mid to late 1990s groups such as the International AIDS Vaccine Initiative and the South African AIDS Vaccine Initiative (SAAVI), placed the development of vaccines against different subtypes on the global agenda. In addition, greater investment went into clinical trials of products in developing countries.
South African AIDS Vaccine Initiative
SAAVI is an autonomous consortium with extensive links to other global HIV vaccine efforts. It has worked extensively with bodies such as the US National Institutes of Health, the HIV Vaccine Trials Network, the Joint United Nations Programme on HIV/AIDS, and the African AIDS Vaccine Programme both to build internal capacity as well as to share expertise, experience, and products. These international bodies have contributed importantly to the funding of SAAVI and the development of South Africa's human and infrastructural capacity.
An example of this positive engagement is the product development and clinical trial programme, which has been funded jointly by SAAVI and the National Institutes of Health. The resultant candidate vaccine will be tested in South Africa and the United States in 2005, the first time this has occurred for a vaccine produced in a developing country. It is also a marker of the increasing collaborative efforts between developed and developing world groups.
South Africa has also been part of other international collaborative efforts. Early strategic investment by the International AIDS Vaccine Initiative to facilitate increased genetic characterisation of the circulating subtype C viruses at the University of Cape Town led to patent protection of South African HIV isolate genes and encouraged the use of these genes in many international HIV vaccine constructs. This foresight and local ownership of HIV gene intellectual property has allowed SAAVI to use the same HIV genes that many other groups are also working on in various candidate HIV vaccine technology platforms. This bodes well for later "prime-boost" clinical trial strategies (where more than one vaccine is used sequentially to induce a stronger immune response). A similar collaboration exists between SAAVI, Stellenbosch University, and Chiron Corporation, through which South African (and Botswanan) HIV genes have been used in Chiron-owned constructs.
International collaboration extends beyond biological product development and clinical trials. Many ethical and sociobehavioural complexities require clarification, and forging links between communities involved in these studies and scientists or clinicians is important. SAAVI has worked closely with international bodies to increase these links and collaborative activities in Africa, India, the United States, and elsewhere.
Maximising international partnerships
International funds for HIV vaccines and clinical trials are increasing steadily, although at an inadequate pace. It has been argued that the magnitude of government and private sector investment in a product is an indicator of the social value that a society attaches to that product. The massive recent investment in vaccine development related to biological warfare, SARS, and avian influenza outbreaks, is an indicator of how great a social value can be attached to vaccines. The speed with which international funds have been mobilised for products protecting society against biological warfare and newly described infectious agents is impressive and laudable. However, we need to replicate that sense of urgency for HIV vaccines, in response to the 60 million people infected or already dead from HIV infection.6
That said, there are promising signs of change. The recent announcement of a possible massive investment in HIV vaccines by the Bill and Melinda Gates Foundation is encouraging because this investment seems to be directed at strategic gaps in the existing global infrastructure and support for HIV vaccine development.7 The probable additional $1bn (￡540m, 811m) investment discussed will inevitably alter the power dynamics in the field and lead to new modes of operating. The European and Developing Country Trial Partnership, a vehicle of the European Union, has also been awarded about 600m (￡400m, $740m) for developing capacity for trials and novel approaches to drugs, vaccines, microbicides, etc for neglected diseases. This is the only major recent announcement of new investment from the developed world in which a fixed minimum proportion (80%) needs to be spent in developing countries. Within the context of increasingly conservative global health (and general) policies, this amount of new funding specifically for developing countries is welcome.
What is certain is that we have not yet managed to raise sufficient resources globally for rapid development of an HIV vaccine. The size and manner of global investment needs a major rethink if we are to respond with the vigour and speed required by this epidemic.
Useful websites
South African AIDS Vaccine Initiative (www.saavi.org.za)
International AIDS Vaccine Initiative (www.iavi.org)
National Institute of Allergy and Infectious Diseases (www.niaid.nih.gov/daids/vaccine/default.htm)
HIV Vaccines Trial Network (www.hvtn.org)
European and Developing Country Trial Partnership (www.edctp.org)
AIDS Vaccine Advocacy Coalition (www.avac.org)
Summary points
Development of vaccines against HIV has been slow
International collaboration and investment is needed for success
The South African initiative shows how resources can be used in developing countries
Future developments
United Nations. AIDS report. New York: UN, 2003.
Dayan GH, Cairns L, Sangrujee N, Mtonga A, Nguyen V, Strebel P. Cost-effectiveness of three different vaccination strategies against measles in Zambian children. Vaccine 2004;22: 475-84.
Bronnenkant L. Panel discussion on vaccine development to meet US and international needs. Strategies for reducing the disincentives to HIV vaccine development: description of a successful public-private sector international collaboration. AIDS Res Hum Retroviruses 1994;10(suppl 2): S311-3.
Burton DR, Desrosiers RC, Doms RW, Feinberg MB, Gallo RC, Hahn B, et al. A sound rationale needed for phase III HIV-1 vaccine trials. Science 2004;303: 316.
McNeil JG, Johnston MI, Birx DL, Tramont EC. Policy rebuttal. HIV vaccine trial justified. Science 2004;303: 961.
Stebbing J, Moyle G. The clades of HIV: their origins and clinical significance. AIDS Rev 2003;5: 205-13
Klausner RD, Fauci AS, Corey L, Nabel GJ, Gayle H, Berkley S, et al. The need for a global HIV vaccine enterprise. Science 2003;300: 2036-9.(Timothy J Tucker, directo)
Correspondence to: T J Tucker saavi@mrc.ac.za
Most work on HIV vaccines is being done in the public sector rather than the pharmaceutical industry. Although international cooperation is producing candidate vaccines, greater investment is needed to speed up progress
Introduction
The processes of developing a vaccine against HIV have been distinct from that of any previous pharmaceutical product. Although most existing vaccine capacity resides within the private sector, most research into an HIV vaccine has taken place (or been funded from) within the public sector. This is because manufacture and distribution of an HIV vaccine is unlikely to generate much profit.3
HIV is a genetically diverse microbe that is categorised into many genetic subtypes. Although HIV subtype B is responsible for a minority of HIV infections, it is the predominant subtype in developed countries.4 Early vaccine development focused on sub-type B genes and proteins, and clinical trials were predominantly in the United States and Europe. However, in the mid to late 1990s groups such as the International AIDS Vaccine Initiative and the South African AIDS Vaccine Initiative (SAAVI), placed the development of vaccines against different subtypes on the global agenda. In addition, greater investment went into clinical trials of products in developing countries.
South African AIDS Vaccine Initiative
SAAVI is an autonomous consortium with extensive links to other global HIV vaccine efforts. It has worked extensively with bodies such as the US National Institutes of Health, the HIV Vaccine Trials Network, the Joint United Nations Programme on HIV/AIDS, and the African AIDS Vaccine Programme both to build internal capacity as well as to share expertise, experience, and products. These international bodies have contributed importantly to the funding of SAAVI and the development of South Africa's human and infrastructural capacity.
An example of this positive engagement is the product development and clinical trial programme, which has been funded jointly by SAAVI and the National Institutes of Health. The resultant candidate vaccine will be tested in South Africa and the United States in 2005, the first time this has occurred for a vaccine produced in a developing country. It is also a marker of the increasing collaborative efforts between developed and developing world groups.
South Africa has also been part of other international collaborative efforts. Early strategic investment by the International AIDS Vaccine Initiative to facilitate increased genetic characterisation of the circulating subtype C viruses at the University of Cape Town led to patent protection of South African HIV isolate genes and encouraged the use of these genes in many international HIV vaccine constructs. This foresight and local ownership of HIV gene intellectual property has allowed SAAVI to use the same HIV genes that many other groups are also working on in various candidate HIV vaccine technology platforms. This bodes well for later "prime-boost" clinical trial strategies (where more than one vaccine is used sequentially to induce a stronger immune response). A similar collaboration exists between SAAVI, Stellenbosch University, and Chiron Corporation, through which South African (and Botswanan) HIV genes have been used in Chiron-owned constructs.
International collaboration extends beyond biological product development and clinical trials. Many ethical and sociobehavioural complexities require clarification, and forging links between communities involved in these studies and scientists or clinicians is important. SAAVI has worked closely with international bodies to increase these links and collaborative activities in Africa, India, the United States, and elsewhere.
Maximising international partnerships
International funds for HIV vaccines and clinical trials are increasing steadily, although at an inadequate pace. It has been argued that the magnitude of government and private sector investment in a product is an indicator of the social value that a society attaches to that product. The massive recent investment in vaccine development related to biological warfare, SARS, and avian influenza outbreaks, is an indicator of how great a social value can be attached to vaccines. The speed with which international funds have been mobilised for products protecting society against biological warfare and newly described infectious agents is impressive and laudable. However, we need to replicate that sense of urgency for HIV vaccines, in response to the 60 million people infected or already dead from HIV infection.6
That said, there are promising signs of change. The recent announcement of a possible massive investment in HIV vaccines by the Bill and Melinda Gates Foundation is encouraging because this investment seems to be directed at strategic gaps in the existing global infrastructure and support for HIV vaccine development.7 The probable additional $1bn (￡540m, 811m) investment discussed will inevitably alter the power dynamics in the field and lead to new modes of operating. The European and Developing Country Trial Partnership, a vehicle of the European Union, has also been awarded about 600m (￡400m, $740m) for developing capacity for trials and novel approaches to drugs, vaccines, microbicides, etc for neglected diseases. This is the only major recent announcement of new investment from the developed world in which a fixed minimum proportion (80%) needs to be spent in developing countries. Within the context of increasingly conservative global health (and general) policies, this amount of new funding specifically for developing countries is welcome.
What is certain is that we have not yet managed to raise sufficient resources globally for rapid development of an HIV vaccine. The size and manner of global investment needs a major rethink if we are to respond with the vigour and speed required by this epidemic.
Useful websites
South African AIDS Vaccine Initiative (www.saavi.org.za)
International AIDS Vaccine Initiative (www.iavi.org)
National Institute of Allergy and Infectious Diseases (www.niaid.nih.gov/daids/vaccine/default.htm)
HIV Vaccines Trial Network (www.hvtn.org)
European and Developing Country Trial Partnership (www.edctp.org)
AIDS Vaccine Advocacy Coalition (www.avac.org)
Summary points
Development of vaccines against HIV has been slow
International collaboration and investment is needed for success
The South African initiative shows how resources can be used in developing countries
Future developments
United Nations. AIDS report. New York: UN, 2003.
Dayan GH, Cairns L, Sangrujee N, Mtonga A, Nguyen V, Strebel P. Cost-effectiveness of three different vaccination strategies against measles in Zambian children. Vaccine 2004;22: 475-84.
Bronnenkant L. Panel discussion on vaccine development to meet US and international needs. Strategies for reducing the disincentives to HIV vaccine development: description of a successful public-private sector international collaboration. AIDS Res Hum Retroviruses 1994;10(suppl 2): S311-3.
Burton DR, Desrosiers RC, Doms RW, Feinberg MB, Gallo RC, Hahn B, et al. A sound rationale needed for phase III HIV-1 vaccine trials. Science 2004;303: 316.
McNeil JG, Johnston MI, Birx DL, Tramont EC. Policy rebuttal. HIV vaccine trial justified. Science 2004;303: 961.
Stebbing J, Moyle G. The clades of HIV: their origins and clinical significance. AIDS Rev 2003;5: 205-13
Klausner RD, Fauci AS, Corey L, Nabel GJ, Gayle H, Berkley S, et al. The need for a global HIV vaccine enterprise. Science 2003;300: 2036-9.(Timothy J Tucker, directo)