Australian Consortium Launches DNA-Fowlpox Trial
On 17 June the first volunteer was vaccinated in an Australian Phase I/IIa trial of a prime-boost strategy that combines DNA- and fowlpox-based HIV vaccines. The trial, which will enroll 24 volunteers, is sponsored by Australia’s National Center in HIV Epidemiology and Clinical Research and will be run at St Vincent’s Hospital (Sydney.)
Fowlpox belongs to the same bird virus family as modified vaccinia Ankara virus (MVA) and canarypox, which have also been developed as HIV vaccine platforms. Volunteers will receive two 1 mg injections (0 and 4 weeks) of a DNA vaccine containing gag, rev, tat, vpu and truncated env genes from HIV-1 clade B, followed by an HIV-fowlbox boost with similar genes at week 8. It is the first study to test a DNA-fowlpox vaccine regimen in HIV-negative volunteers. A therapeutic trial of fowlpox vaccine also containing IFN-gamma, an immune-modulating cytokine, was conducted in HIV-positive individuals in 2002. Because participants in this study were on antiretroviral therapy, which reduces viral load, it was difficult to determine the benefits of the vaccine-cytokine combination, although a follow-up study is now underway to assess control of viral load off therapy. Another preventive trial of similar vaccines containing HIV genes from the CFR_01AE recombinant, Thailand’s main circulating strain, is planned for Thailand later this year.
New Proposal for a Global AIDS Vaccine Enterprise
In an article titled, “The Need for a Global Vaccine Enterprise” (Science 300:2036;2003), 24 of the world’s leading vaccine researchers and advocates called for a major effort to expand and restructure the search for an AIDS vaccine. Richard Klausner, Executive Director of the Bill & Melinda Gates Foundation global health program, was lead author on the paper.
The proposal calls for a coordinated effort similar to the Human Genome Project, which divided and assigned roles to a diverse group of scientists to meet its goal. Similarly, the new vaccine enterprise would map out the entire “grid” of potential vaccine approaches. It would then assign tasks, allocate funds and ensure that participating teams of researchers collectively covered the entire grid. To accomplish this, the enterprise would establish of new Vaccine Development Centers (VDCs), which could be actual institutes or virtual collaborations. The paper pointed out that VDCs could include efforts sponsored by existing funders, such as the National Institutes of Health, IAVI and the European Union—all of whom were signatories to the article—could participate in the enterprise.
The VDCs would be part of an interconnected network that also includes manufacturing facilities, central laboratories, and clinical trial sites capable of enrolling a projected figure of 35,000 volunteers into clinical studies each year. The paper did not specify funding requirements or sources for this massive endeavor. In August, major vaccine stakeholders gathered at a Washington, D.C. meeting hosted by the Bill & Melinda Gates Foundation and formed six working groups (product discovery, product development, standardization of assays, manufacturing, clinical trials capacity, and international regulatory and licensing issues) which will contribute to strategic framework.
African AIDS Vaccine Programme Meets in Ethiopia
On 13-16 June nearly 200 scientists, trial investigators, national authorities, and community representatives from Africa and around the world gathered for the second meeting of the African AIDS Vaccine Programme, “Strategies for the Development of HIV Vaccine Trial Sites in Africa: Challenges and Opportunities.” The meeting’s focus reflected “anticipation of a new wave of candidate HIV vaccines based on strains prevalent in Africa,” said Jose Esparza, head of the WHO-UNAIDS vaccine program. AAVP’s primary funder. The meeting included intensive discussion of ethical issues, such as standard of care for trial participants and communities, and enrollment of women and adolescents, there were also updates on AAVP activities. In 2002, AAVP completed an assessment of the needs and capacities of African ethical review committees, developed a consensus document on clade (seearticle) and established a working group on community issues. Looking ahead, AAVP plans to develop a template for national vaccine plans.
First HIV vaccine trialS get green light in South Africa
On 6 June 2003, the South African Medicines Control Council approved the country’s first HIV vaccine trial, and the first clinical trial of a vaccine based on clade C. The Phase I study (HVTN 040) will test the safety and immunogenicity of a candidate based on a Venezuelan equine encephalitis (VEE) vector containing HIV-gag from a South African clade C isolate. Clade C strains cause nearly all infections in South Africa, and about 47% worldwide.
The vaccine was developed by Bob Johnston (University of North Carolina, Chapel Hill) and AlphaVax, a biotechnology company (Research Triangle Park, North Carolina). The VEE vector is derived from a vaccine designed to protect humans against a South American virus that often causes disease in horses. It targets mainly dendritic cells, which play a key role in inducing immune responses.
In August, the MCC approved a second Phase I trial (IAVI 011). This IAVI-sponsored study will test the safety and immunogenicity of HIVA.MVA, a candidate based on modified vaccinia Ankara virus (MVA) and containing a clade A gag consensus sequence plus a string of CTL epitopes from the gag, pol, nef and env genes. It was designed by scientists at the University of Nairobi and University of Oxford.
The two trials will be conducted separately, but at the same South African sites: one in Soweto, the other in Durban.
HVTN 040 will evaluate three different vaccine doses in a total of 96 volunteers. Testing will begin in the US and proceed in South Africa once safety is established.
IAVI 011 will take place at two European sites along with Durban and Soweto, and enroll 111 volunteers. HIVA.MVA is being studied alone and as part of a prime-boost combination with a DNA vaccine in Kenya, Uganda and the UK.