A decade after HIV was identified as the cause of AIDS, the Rockefeller Foundation convened a meeting of 24 authorities on the disease in Bellagio, Italy, to discuss what had stalled progress toward the development of a preventive vaccine against the virus.
Two themes dominated that meeting. First, it was clear that the institutions most capable of developing an AIDS vaccine, particularly pharmaceutical firms, lacked the financial incentive to pour sufficient resources into the task. Second, none of the handful of AIDS vaccine candidates then under development was devised to protect people from variants of HIV common in developing countries, which were already on the frontlines of an exploding pandemic.
Getting Started
The International AIDS Vaccine Initiative was the fruit of these discussions. Launched at the start of 1996 as a non-profit public-private product development partnership (PDP), IAVI immediately began tackling the issues identified at the Bellagio meeting. As a PDP, it would, through partnerships with commercial vaccine manufacturers, have access to all the experience stored in their research wings but would not be hindered by commercial demands that had stymied private investment in AIDS vaccine development.
IAVI’s first challenge was to make AIDS vaccine development a priority on the global public health agenda. With the support of 70 organizations in 23 countries, IAVI helped build an advocacy initiative that resulted in the G8 issuing a "Call for Action" on HIV vaccines in 1997. The following year, the young PDP produced the first Scientific Blueprint for AIDS Vaccine Development, which called for greater international collaboration to fast-track the parallel development of multiple HIV vaccines, and for a stronger focus on vaccine candidates devised to combat strains of HIV circulating in Africa and Asia.
Productive Partnerships
By the turn of the century, backed by the support of a growing group of donors and partners, IAVI was poised to play a more direct role in testing candidate AIDS vaccines. But it would have to first build the capacity to conduct clinical trials in developing countries, where most of those studies would take place.
Over the next few years, IAVI built a network of clinical trial research centers in southern and eastern Africa, beginning with Kenya. The organization conducted its first clinical trial of a candidate vaccine in collaboration with the Kenya AIDS Vaccine Initiative and the UK’s Medical Research Council.
It also established a Human Core Immunology Laboratory in London to help coordinate the trials it would be running in Africa and Asia. The Human Immunology Lab helps to train staff at the network’s research centers and to standardize methods and reagents for research, ensuring that the data generated by labs supported by IAVI are comparable at all times. IAVI has harnessed the network of clinical trial centers it supports to put six novel vaccine candidates into clinical trials in 11 countries.
As IAVI has prepared to conduct vaccine trials, it has worked closely with partners to cultivate a favorable environment for those trials in host countries. These initiatives were key to the smooth launch of vaccine trials in India, Uganda and other African nations, and were consolidated within IAVI in 2003 in the Country and Regional Programs (CRP) department.
Through CRP, IAVI establishes links with governments to support the development of effective HIV- and AIDS-related policies. The department also works in partnership with local grassroots organizations to advocate for the development of AIDS vaccines; enhance recruitment for clinical trials; cultivate an atmosphere of trust between researchers and local communities; and to shore up voluntary counseling and testing (VCT) and other HIV and AIDS health services in host countries.
Moving Upstream
For much of its history, IAVI has focused on the clinical assessment of vaccine candidates developed through partnerships. More recently, the organization has become increasingly engaged in translational research aimed at designing new HIV vaccine candidates.
Perhaps the most critical roadblock to the development of an effective AIDS vaccine arises from HIV’s uncanny ability to avoid neutralization by antibodies. However, a handful of antibodies capable of shutting down the many variants of the virus have been isolated from HIV-infected individuals.
Hoping to find clues about how best to design an AIDS vaccine, IAVI in 2002 launched the Neutralizing Antibody Consortium (NAC)—a collaboration between IAVI’s staff scientists and some of the most accomplished HIV researchers in the world—to study those antibodies.
Work done within the NAC has since exposed not only how each of the known neutralizing antibodies manages to shut down HIV, but also how the virus shields its vulnerable spots from immune attack. This information is now being harnessed by NAC scientists to devise new approaches to developing AIDS vaccine candidates.
IAVI also established a consortium to develop better vehicles for the delivery of AIDS vaccine candidates. For safety reasons, most of the existing vaccine candidates against HIV are delivered to people as synthetic copies of HIV genes that have been inserted into viruses, such as the canary pox virus, that cannot cause disease in humans. IAVI’s Vector Design Consortium—a collaboration between its own researchers and those at external institutions—is dedicated to improving such vehicles of vaccination.
A third collaboration established by IAVI, the Live Attenuated Consortium (LAC), explores the immune mechanisms by which non-human primates suppress simian AIDS after they’ve been inoculated with killed simian immunodeficiency virus (SIV).
The Way Forward
To coordinate these efforts and provide crucial material and logistical support to the wide-ranging consortia, IAVI in 2008 established its AIDS Vaccine Design and Development Laboratory in New York City. Staffed with researchers who have extensive experience in industry, the lab will play an important role in converting the research done within IAVI’s consortia into viable vaccine candidates.
Developing an effective AIDS vaccine is among the greatest scientific challenges facing our generation. Through dynamic partnerships with a variety of public, private and governmental organizations, IAVI has established a strong presence in every aspect of AIDS vaccine research and development and has brought unprecedented focus to solving this urgent problem.