Last year saw 13 new trials of preventive AIDS vaccines launched in eight countries around the world. As of January 2007, a total of 33 AIDS vaccine trials were underway in 24 countries, covering every continent, notes the latest overview from the International AIDS Vaccine Initiative (IAVI).
All of the trials started in 2006 were either Phase I or Phase I/II studies assessing the safety and immunogenicity of candidate vaccines. They included the first AIDS vaccine trials in the Russian Federation and Zambia, as well as new studies in Kenya, Uganda, Tanzania, the US, the UK, Sweden and Peru. Many of these were sponsored by new research organisations, such as Sweden’s Karolinska Institute, St George’s University of London and the Moscow Institute of Immunology.
One of the Phase II trials was launched by IAVI in Uganda and Zambia, part of a multicentre study of tgAAc09, an adeno-associated viral-based prophylactic vaccine under development with US biotech Targeted Genetics. Data from the study, which also includes three sites in South Africa, should be out later this year.
One vaccine in Phase III
Despite the increased development activity, only one AIDS vaccine candidate is in Phase III efficacy trials. This is a combination of French vaccine specialist Sanofi-Pasteur’s ALVAC-HIV (vCP1521) and US biotech VaxGen’s AIDSVAX, with the latter serving as a booster. The Phase III study began in October 2003 and is running at eight sites in Thailand. ALVAC contains HIV genes inserted into a canarypox virus that is harmless to humans, while AIDSVAX is based on a synthetic version of gp120, a protein on the surface of HIV.
AIDSVAX used alone was the first preventive AIDS vaccine to enter Phase III trials. Hopes were dashed in November 2003, however, when VaxGen reported that the vaccine had failed to reach either its primary endpoint of preventing HIV infection in more than 2,500 injecting drug users in Thailand, or its secondary endpoint of slowing disease progression in immunised participants who later became infected with the virus.
VaxGen’s development programme had already suffered a blow in February 2003 when initial results from a study of AIDSVAX in North Americans and Europeans failed to show protection against viral transmission across the general population.
IAVI/Targeted Genetics’ tgAAc09 is one of four AIDS vaccine candidates in Phase II trials. The others are two vaccine components – VRC-HIVDNA-116-00-VP and VRC-ADV-014-00-VP, given as a primer and booster respectively – developed at the US National Institute of Allergy and Infectious Diseases’ (NIAID) Vaccine Research Center (VRC) in collaboration with US companies Vical and GenVec; LIPO-5, developed by the French National Agency for Research on AIDS and Viral Hepatitis (ANRS) and Sanofi-Pasteur; and the NIAID/Merck & Co’s MRKAd5 HIV-1 Gag/Pol/Nef vaccine.
According to IAVA, the adenovirus serotype 5 vaccine under development by Merck is one of the most advanced candidates in the field after the ALVAC-HIV/AIDSVAX combination. Data from the US company’s ongoing Phase IIb proof-of-concept trial are expected in 2008-09, while an additional Phase IIb trial with MRKAd5 HIV-1 Gag/Pol/Nef is due to begin shortly in South Africa.