IAVI Outlines R&D Plans for Next Two Years
By Patricia Kahn, Ph.D.*
At the Barcelona meeting, IAVI released its Research and Development Agenda 2002-2004.
The Agenda is a blueprint for activities in several key areas and encompasses issues ranging from pre-clinical development to large-scale manufacturing of a licensed vaccine.
The first area of focus is identifying and addressing some of the obstacles to vaccine development. On the pre-clinical front, the key hurdle IAVI will tackle is the lack of candidates able to induce antibodies that neutralize a broad range of primary HIV strains. Solutions will be sought through the recently-established Neutralizing Antibody Consortium, founded by IAVI in 2002 to accelerate progress on a variety of approaches and to foster close collaboration among leading labs working on the problem from different angles.
A second set of obstacles concerns the eventual manufacture and rapid delivery of a licensed vaccine. The R&D agenda lays out plans to invest in developing new technologies that will be needed to mass-produce, as cheaply as possible, hundreds of millions of vaccine doses based either on DNA or on viral vectors. A related goal, to be pursued together with regulatory bodies and global health organizations, is the creation of a regulatory template that identifies core requirements which an AIDS vaccine must meet for licensure.
Another focus is broadening the clinical pipeline. Here, IAVI will continue to work on developing candidates that induce broader and more durable cellular immune responses, by optimizing designs for DNA vaccines and viral vectors systems, including modified vaccinia Ankara (MVA; already in human trials), Semliki Forest Virus (SFV) and adeno-associated virus (AAV). Studies in rhesus macaques will play a major role in evaluating these candidates. In addition, IAVI is planning clinical studies to help determine whether mucosal immunity is necessary for protection. Here, the strategy is to compare a DNA vaccine delivered by bacteria given orally (which is likely to induce mucosal responses) with the same vaccine injected as naked DNA, which is not expected to induce these responses. Work on these candidates will emphasize HIV subtypes prevalent in the most afflicted regions and involve intellectual property agreements that permit eventual technology transfer to developing countries and keep prices to a minimum.
The Agenda also outlines plans for moving the most promising candidates into large-scale efficacy studies. Important milestones include advancing a DNA-MVA candidate vaccine (now in Phase I/II trials) to Phase III trials by the end of 2004 and identifying two other “second generation” candidates for accelerated clinical development, with the goal of starting efficacy trials by 2007. IAVI’s core immunology laboratories for evaluating blood samples from human and non-human primate studies will provide a standard foundation for IAVI trials, and for the broader field.
*Patricia Kahn, Ph.D., is editor of the IAVI Report.