Resetting Expectations in the Search for an AIDS Vaccine
In its AIDS Vaccine Blueprint 2008, IAVI proposes a series of interim milestones to help overcome the biggest challenges facing the AIDS vaccine field today
MEXICO CITY, August 5, 2008 – With the release of its AIDS Vaccine Blueprint 2008 at the International AIDS Conference today in Mexico City, the International AIDS Vaccine Initiative (IAVI) sought to reset both expectations and focus in the search for an AIDS vaccine.
“The quest to develop an AIDS vaccine is at a pivotal moment. In the wake of the failure of a leading AIDS vaccine candidate nearly a year ago, some have questioned whether we will ever have an AIDS vaccine,” said Dr. Seth Berkley, President and CEO of IAVI. “To these skeptics, I say that developing an AIDS vaccine may take more time and innovation than we might have once imagined, but we are confident that science will prevail. The necessary direction for the field is clear, and we must march forward. Future generations are counting on us to bring this epidemic to an end.”
IAVI’s Blueprint aims to set the record straight about the current state of AIDS vaccine research and development and offers a series of interim goals to bring the field closer to the ultimate goal — a safe, effective and accessible AIDS vaccine. It proposes progress be measured against these shorter-term scientific milestones.
“Twenty-five years since the discovery of HIV as the cause of AIDS, nearly 7,500 people continue to become infected with HIV each day,” said Dr. Peter Piot, Executive Director of the Joint United Nations Programme on HIV/AIDS. “I am encouraged and inspired to see that IAVI’s AIDS Vaccine Blueprint proposes a well-defined roadmap to accelerate the development of a critical tool for the elimination of this terrible disease.”
The Blueprint acknowledges that much work remains to be done before an AIDS vaccine will be in hand, but details the considerable advances that have been made and the exciting prospects ahead. The document notes that this base of science forms the foundation for the considerable work that is going forward.
“Strong scientific evidence in both humans and animal models suggests that developing an AIDS vaccine is possible,” said Dr. Wayne Koff, Senior Vice President of Research and Development at IAVI. “The challenge we face now is how to translate advances made in our understanding of the virus and the human immune responses to it into promising vaccine candidates as quickly and safely as possible.”
“The HIV vaccine research field is at a crossroads. Now is the time to integrate new ideas and new technologies from other areas of biomedical research, to energize the field with a new generation of researchers and to undertake an ambitious program of research aimed at understanding the full complexity of the human immune response to HIV,” said Dr. Alan Bernstein, Executive Director of the Global HIV Vaccine Enterprise. “IAVI's Blueprint lays out a clear and realistic roadmap, with intermediate milestones, of important aspects of where the field needs to go over the next few years.”
IAVI has prioritized the following Blueprint recommendations:
- Solve the Neutralizing Antibody Problem: Most vaccines work by neutralizing the virus with antibodies before an individual can become infected with a pathogen. An AIDS vaccine is likely to be no exception. To date, researchers have identified neutralizing antibodies against HIV. They are now trying to figure out how to design immunogens that generate similar antibodies. To speed the discovery of an immunogen that can neutralize a substantial proportion of circulating HIV strains, existing programs focused on the neutralizing antibody problem should be scaled up.
- Solve the Cell Mediated Immunity (CMI) Problem: One of the lessons of the Merck trial is that inducing effective CMI responses will be more challenging than originally envisioned and may be as challenging as solving the neutralizing antibody problem. We do know, however, that there are rare individuals, known as elite controllers, who are infected with HIV, but are able to keep the virus in check for decades without any sign of disease. What’s more, non-human primates vaccinated with a live, but weakened form of the simian equivalent of HIV (known as SIV) mount an immune response that protects them from SIV disease. More resources should be devoted to studying the mechanisms behind both of these phenomena, which could provide vital clues for improved vaccine design.
- Trim and Improve the Pipeline: Current and future AIDS vaccine candidates need to be compared and prioritized in comparison to tested vaccines. Those vaccines that cannot demonstrate superiority should be dropped. Resources from these candidates should be freed and re-directed towards solving the key scientific problems currently impeding the development of the next generation of AIDS vaccine candidates. Those candidates that do meet pre-defined, mutually-agreed upon criteria, on the other hand, should be tested in rapid, small test-of-concept trials before they are moved into conventional large scale efficacy trials. To improve the pipeline, IAVI also recommends accelerating the development of replicating vector-based vaccines. It is likely that the impressive level of protection afforded by live-attenuated SIV in non-human primates is at least partially due to its replicative nature. Because of the novel regulatory and risk-benefit questions that these vectors will likely raise, replicating vectors have received little attention to date.
- Sustain the Effort: The development of an AIDS vaccine continues to be one the greatest needs of the 21st century and one of science’s greatest challenges. Ensuring adequate clinical trial and human capacity, providing incentives for innovation, training the next generation of researchers and securing long term stable and flexible funding are all necessary for success.
“Developing a preventive HIV/AIDS vaccine is going to be much tougher than we originally thought. And we need as many people as possible committed to helping us reach this goal. The world is now relying on the talents, resources and energy of researchers, donors, policymakers, activists and other stakeholders from both the developed and the developing world to help sustain this vital effort,” said Dr. Omu Anzala, Associate Professor at the University of Nairobi School of Medicine and Director of the Kenya AIDS Vaccine Initiative.
“We’ve come a long way in AIDS vaccine discovery and development, but recognize that there’s a long road ahead and there will be further bumps on that road. IAVI’s Blueprint is intended to stimulate debate within the field that we hope will generate consensus on the most promising way forward,” said Berkley. “We at IAVI will keep using speed, flexibility and focus to drive forward AIDS vaccine science and testing, and to keep an AIDS vaccine on the center stage as a long-term solution to this devastating public health problem.”
The International AIDS Vaccine Initiative (IAVI) is a global not-for-profit organization whose mission is to ensure the development of safe, effective, accessible, preventive HIV vaccines for use throughout the world. Founded in 1996 and operational in 24 countries, IAVI and its network of collaborators research and develop vaccine candidates. IAVI's financial and in-kind supporters include the Alfred P. Sloan Foundation, the Bill & Melinda Gates Foundation, the Foundation for the National Institutes of Health, The John D. Evans Foundation, The New York Community Trust, the James B. Pendleton Charitable Trust, The Rockefeller Foundation, The William and Flora Hewlett Foundation; the Governments of Canada, Denmark, Ireland, The Netherlands, Norway, Spain, Sweden, the United Kingdom, and the United States, the Basque Autonomous Government as well as the European Union; multilateral organizations such as The World Bank; corporate donors including BD (Becton, Dickinson & Co.), Bristol-Myers Squibb, Continental Airlines, Google Inc., Henry Schein, Inc., Merck & Co., Inc. and Pfizer Inc; leading AIDS charities such as Broadway Cares/Equity Fights AIDS and Until There's A Cure Foundation; other private donors such as The Haas Trusts; and many generous individuals from around the world. For more information, see www.iavi.org.