This entry in our series on “Vaccines: The Next 10 Years” comes from Seth Berkley, founder and CEO of the International AIDS Vaccine Initiative:
I was asked by the ONE blog to share my thoughts about where global efforts to develop AIDS vaccines are headed in the coming decade and how the International AIDS Vaccine Initiative (IAVI), which I lead, plans to contribute to the endeavor. For researchers working toward a preventive AIDS vaccine, recent months have provided very promising news. Last year, an experimental vaccine tested in Thailand proved to be effective at preventing HIV infection. The vaccine regimen, with around 30% efficacy, was not as protective as we’d like any vaccine to be, but the trial result was notable because it established, for the first time, that a vaccine could protect humans from HIV infection. So the Thai trial results tell us we can make an AIDS vaccine. The challenge now is to devise one that is considerably more effective.
Essentially, there are two approaches to doing that. One is to test candidates using current approaches to AIDS vaccine design, including regimens similar to the combination of two candidates that were tested in the Thai trial. That results of the Thai trial were a surprise is instructive. Based on earlier animal and early-stage human studies of the two vaccine candidates used, many researchers expected no protective effect. That there was modest protection underscored the importance of human efficacy trials.
Today, the capacity to test experimental AIDS vaccines exists on six continents. IAVI’s niche is accelerating the development and testing of such vaccine candidates for the developing world; the organization was established to ensure the development of AIDS vaccines and to ensure that they would be available and accessible in the developing world where the burden of AIDS is greatest. To ensure that a vaccine would work in and be acceptable to developing countries, IAVI engages researchers, policymakers and civil society in those countries in the AIDS vaccine effort. Specifically, we support local clinical research centers in Africa and India that together make up a network that has put a variety of candidate vaccines through clinical trials over the past decade. Given sufficient resources, the scientists at these centers, trained to the highest standards of clinical practice, will be well-prepared for the new studies that will follow in the wake of the Thai trial results.
An important question is which of the couple dozen vaccine candidates in various stages of development, and which possible modifications of the Thai trial candidates, should be given priority for advanced testing. One hope is that data from the Thai trial will shed light on these matters. Researchers are putting their heads together and examining the data, hoping it will reveal which animal experiments and lab tests best predict whether a vaccine candidate will prove efficacious in humans, information that would help researchers decide which candidates to advance. Scientists are also studying data and samples from the trial trying to determine precisely how the vaccine candidates worked. That information could tell us whether other existing candidates fit the bill and could also inform the development of future candidates.
That gets us to the second approach to today’s challenge in AIDS vaccine development: creating a new generation of vaccine candidates that potentially offers greater promise. While we must continue testing the approaches we have, looking for a breakthrough and learning from the process, the technological leaps of our age also offer the opportunity to be more ambitious, to explore entirely new concepts for potentially creating a very powerful AIDS vaccine. These include using retrovaccinology to design a vaccine that produces antibodies that neutralize a broad spectrum of HIV variants, what many researchers consider the most pressing challenge facing the field today. Or constructing a vaccine using replicating viruses as vectors to carry HIV genes, so as to ensure a robust response by the immune system. Or building a vaccine that induces immunity in the lining of the gut, where HIV establishes an early beachhead.
These are all areas of increased focus for IAVI’s R&D; investments. IAVI’s mission is to ensure the development of an AIDS vaccine, not necessarily to develop one ourselves. So our investments in these explorations are directed not only toward IAVI scientists but also toward other researchers and institutions involved in the same quest. Last year, this model of collaboration paid off when scientists at and affiliated with IAVI — including from The Scripps Research Institute in La Jolla, California and from many research centers in the developing world — were part of the second big advance in the field: the discovery of new broadly neutralizing antibodies against HIV, the first such antibodies to have been discovered in more than a decade. These antibodies reveal sites on HIV that may provide important new targets that researchers can use when designing candidate AIDS vaccines. Using our collaborative model, we are also pursuing non-vaccine approaches to delivering these powerful antibodies to individuals at risk of HIV infection.
Of course, none of this answers the question I almost always get when I address the subject of a future AIDS vaccine: when are we going to have one? Unfortunately, that question is unanswerable. The timeline depends on scientific breakthroughs that are impossible to predict. In describing where we are today, I can’t say it better than Michel Sidibé, executive director of the Joint United Nations Programme on HIV/AIDS (UNAIDS), who told participants last year at an AIDS vaccine conference, “It is clear that your perseverance is paying off. One cannot predict the duration of your journey to licensable HIV vaccines, but one does begin to feel that the wind is in your sails.”