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Vol 9 No 2




MU to Collaborate on Largest Ever HIV Vaccine Trial

Plan Unveiled at 14th International Conference on AIDS in Barcelona

by Prof. Emeritus Dr. Prasert Thongcharoen,
Faculty of Medicine, Siriraj Hospital

     Several important advances were made in the fight against the global HIV/AIDS epidemic at the recent 14th International Conference on AIDS, held in Barcelona, Spain, which was attended by a large MU delegation consisting of 25 executives, staff and graduate students from the Faculties of Tropical Medicine, Science, Graduate Studies, Public Health, Medicine Siriraj Hospital, Medicine Ramathibodi Hospital, and the Institute for Population and Social Research. For the first time, specific attention was focussed on HIV/AIDS and women, as it was recognized that medical research related to women significantly lagged behind that of men, and more research was called for. Also for the first time, a special 'leadership track' was held, co-hosted by luminaries Bill Clinton and Nelson Mandela, to attract political commitment to fight HIV/AIDS. A new 'World Leaders AIDS Network' was established.

     No less important, for the first time an official satellite gathering was held, organized by the 'International AIDS Vaccine Initiative', to address all aspects of HIV vaccine development, with Thailand playing a lead role. Dr. Supachai Rerks-Ngarm of the Thai Ministry of Public Health, Principal Investigator for a Phase III 'Prime Boost' HIV vaccine trial, presented a groundbreaking proposal - the largest ever community-based HIV vaccine trial. MU's Faculty of Tropical Medicine is a key collaborator on the massive project, which is jointly funded by the US and Thai governments. Other collaborators include the Ministry of Public Health, the US Military HIV Research Program, the Royal Thai Army Medical Department, the US National Institute of Allergy and Infectious Diseases, the Henry Jackson Foundation, and the companies Aventis Pasteur and VaxGen.

     The project involves a randomized, double-blind and placebo-controlled vaccine trial and is expected to last more than 5 years. Specifically, it seeks to determine the effectiveness of a 'prime-boost' combination using ALVAC-HIV (vCP1521), a canarypox vaccine made by Aventis Pasteur, as a 'prime' (that is, an initial dose) followed by a 'boost' (a supplementary dose) of AIDSVAX-B/E, a gp-120 subunit vaccine made by VaxGen. Both vaccine strategies have been studied in thousands of people globally and have excellent safety records; it is impossible to contract HIV from either vaccine.

     ALVAC-HIV is a live recombinant canarypox vector into which selected HIV genes are inserted. Because canarypox can neither cause disease in humans nor integrate into the genome, it is attractive as an AIDS vaccine technology. The vaccine is designed to work against a primary subtype E isolate, which is specific to the HIV strain prevalent in Thailand. The canarypox stimulates cellular immunity by activating Cytotoxic T lymphocytes, which recognize and kill HIV-infected cells.

 HIV/AIDS VACCINE TRIALS IN THAILAND

 Stage of Trial

Experimental 
HIV/AIDS Vaccine

Date of First Vaccination

 Number of Volunteers
Phase 1

HIV-1 MN  Synthetic Peptide

 6-Jun-94

30 
Phase 1/2

HIV-1 MN rgp 120

 21-Feb-95

 33
Phase 1

 HIV-1 SF2 gp120

 29-Aug-95

 54
Phase 1

  HIV-1 Immunogen (Remune)

 29-Mar-96

 30
Phase 2

 HIV-1 Immunogen (Remune)

 27-Aug-97

 297
Phase 1/2

 HIV-1 ThaiE gp120

 10-Nov-97

 380
Phase 1/2

 AIDSVAX B/E

 16-Feb-98

 92
Phase 3

  AIDSVAX B/E

 24-Mar-99

 2,500
Phase 1/2

 ALVAC/ThaiE gp160 or ThaiE gp120

 24-Feb-00

 130
Phase 1/2

 ALVAC/AIDSVAX B/E

 8-Mar-00

 125

     AIDSVAX B/E is made from gp 120, a synthetic clone of a protein found on the surface of HIV, and contains no genetic material. Using recombinant DNA technology, the gene for gp120 is cloned and then duplicated by Chinese hamster ovary cells in commercial-scale fermenters. The gp120 is then purified and mixed with alum, an adjuvant that intensifies the immune response. It was specifically designed for the subtype E prevalent in Thailand. AIDSVAX stimulates humoral immunity as measured by antibody production.

     The hope is thus that both arms of the immune system - humoral, involving antibodies, and cellular - will be stimulated by using the two vaccines, resulting in protection against infected cells and freely circulating virus.

     The trial protocol calls for 16,000 HIV-uninfected volunteers from Chon Buri and Rayong provinces aged 20 to 30 years. Half the trial participants will receive a dose of ALVAC-HIV at 0, 1, 3 and 6 months along with doses of AIDSVAX at 3 and 6 months. The other half will receive placebo injections at all 4 vaccination visits.

     The trial is expected to begin by the end of 2002, and take a year to enroll the volunteers, who will receive extensive counseling on HIV risk avoidance. The immunization phase will take 6 months, with follow-up for 3 years thereafter. After the vaccination phase, the volunteers will have their blood drawn routinely every 6 months to determine if they have become infected by HIV. Final analysis of the trial results is expected in 2008.

     The Clinical Trial Center of MU's Faculty of Tropical Medicine, led by Dr. Punnee Pitisuttithum, will be responsible for monitoring volunteers and recording any adverse events resulting from vaccination throughout the trial. Dr. Punnee and her team have extensive experience in other HIV vaccine trials conducted in Thailand (see chart), including an ongoing Phase III trial jointly run by VaxGen and the Bangkok Metropolitan Administration. The Clinical Trial Center was founded a decade ago with the assistance of the World Health Organization.

     Although Thailand has had dramatic success in HIV/AIDS intervention programs over the last decade - reducing the rate of new infections from some 120,000 in 1991 to 25,000 in 2001 - the figure remains too high. Another factor of great concern is that new infections seem to be occurring in the adolescent population, thus further studies in this area are needed. The development of a safe, effective and affordable HIV vaccine will certainly help supplement and strengthen existing intervention measures, and contribute to the ongoing worldwide battle against this devastating pandemic.

     In keeping with the country's significant role in global HIV/AIDS research, Thailand will play host to the 15th International Conference on AIDS, scheduled to be held on 16 - 21 July 2004 at the Impact Arena in Bangkok. The Conference will be co-hosted by the International AIDS Society and the Ministry of Public Health of the Royal Thai Government. Prof. Emeritus Dr. Prasert Thongcharoen of MU's Faculty of Medicine, Siriraj Hospital, is serving as the Co-chairman for Scientific Issues for the event, while Senator Mechai Viravaidya of the Royal Thai Senate is serving as Co-chairman for Community Issues. In addition, numerous MU staff members with expertise in HIV/AIDS-related fields are also involved in organizing the Conference, an important next step forward in the struggle against HIV/AIDS.

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