A joint session of the Australasian Society for HIV Medicine and ICAAP
on Sunday 7 October gave a progress report on the new AIDS vaccines which are being developed in Australia with US government funding (as an NIH Vaccine Design and Development Team), for full-scale testing in Thailand within the next ten years. This project was also discussed at a WHO-UNAIDS sponsored satellite meeting on vaccines held immediately after ICAAP on Thursday 11 October.
The Australian project is a unique collaboration between public sector, private sector and community organisations, with social researchers as well as biomedical researchers taking part from the very beginning. In Sydney, 2,000 gay men are to be recruited into a cohort study to find out if it will be possible to run a vaccine efficacy trial in Australia as well as in Thailand. The Australian study will also seek to find out more about patterns of risk-behaviour and how these might be affected by the future availability of a vaccine.
The vaccine system uses a DNA vaccine as a primer, followed by a recombinant fowlpox vaccine used as a vector (carrier) for unrelated genes. The fowlpox vector is based on a vaccine produced by Australian government veterinary researchers for use in chickens. To make this a little easier to understand, the researchers have called it the “Double Whammy”. (It is similar in outline to the vaccines now being developed and tested in Oxford and Nairobi, supported by the International AIDS Vaccine Initiative, although the two projects are using different poxviruses, different DNA designs, and different HIV genes.)
The Australian DNA vaccines include a sequence called CpG which appears to promote immune responses. Their fowlpox vaccines may include additional human gene sequences, coding for either gamma interferon or interleukin 12 (depending on the results of animal studies) to promote cellular immune responses.
The HIV-related component of all vaccines will include a mutated gag-pol sequence and env. The regulatory genes tat and rev will be included in the DNA vaccines and in the Thai version of the fowlpox vaccine. The vaccines to be tested in Sydney will use subtype B gene sequences and those for Thailand will use A/E sequences, matching the viruses circulating most widely in Thailand.
Where the research goes next
In addition to the vaccines for testing in Australia and in Thailand, another version will be based on an SHIV that causes disease in monkeys, to test the ability of this vaccine approach to protect against disease.
Additional research, in mice and in monkeys, will investigate ways to deliver the vaccines to enhance mucosal immune responses, starting with intranasal delivery which, in some vaccines in mice, stimulates responses in the genital areas.
The first prototypes have already been designed and manufactured to clinical standards and have only to complete animal safety testing before the first trial can start, scheduled for August 2002 in low-risk Australian volunteers.
The first Thai clinical trial, to be run by the Thai Red Cross, is due to begin in 2003. Full scale testing will inevitably take several years after that, and will require further international funding.
The intellectual property in the vaccines is jointly owned by all partners in the consortium that is developing it, including the Australian Federation of AIDS Organisations (AFAO) representing the community response to HIV and AIDS in Australia. AFAO has declared that its goal (shared by other partners in the consortium) is the widest possible access in developing countries to any useful product of this work; they will be working with Thai partner organisations to ensure this.