Giving It His Best Shot
BIDMC Researcher Relentlessly Pursues the Search for an AIDS Vaccine
In the early 1980s, doctors first described the symptoms of a disease that would ultimately define a generation. Now more than three decades later, AIDS represents both the daunting range of obstacles that can arise from a deadly epidemic and the power biomedical science can have in the face of those complexities.
On the one hand, AIDS remains the greatest infectious disease challenge of our age; more than 65 million people worldwide have been infected and more than 30 million have died since the epidemic began. On the other, we have witnessed the development of more drugs to treat HIV, the virus that causes AIDS, than for all other viruses combined; these drugs have saved countless lives but also fostered a sense of complacency around finding ways to eliminate the disease once and for all.
It is in this precariously balanced world of HIV/AIDS that Dan H. Barouch, M.D., Ph.D., continues his relentless pursuit of trying to understand what makes this disease tick and how it might be ultimately defeated. “There’s no question that the perceived level of urgency in the U.S. is lower now than before effective anti-retroviral therapy existed,” says the director of Beth Israel Deaconess Medical Center’s new Center for Virology and Vaccine Research (CVVR). “But I would say that the level of urgency in communities in sub-Saharan Africa is as high now as ever before.” In that part of the world, infections continue to occur at a staggering pace; but even in the United States the rate of new infections has not fallen over the past decade and at least one-third of Americans living with the disease do not have access to the care they need.
“Treatment is life-saving for those people receiving it, but drugs probably won’t end the global epidemic,” says Barouch. “If you look at the global statistics for AIDS —for every two patients put on therapy, five more have become infected. And with the current economic climate, it looks unlikely that there’s going to be any massive increase in foreign spending so getting treatment to everybody who needs it at this point would be very difficult.” In light of these facts, Barouch and many of his infectious disease counterparts firmly believe that the only definitive solution to the worldwide HIV epidemic is a vaccine, which was the seminal advance in prior eras for controlling pathogens such as smallpox and polio.
But when it comes to HIV, making vaccination history repeat itself has been problematic. First and foremost, the disease-causing agent itself is far more complex. “The genetic diversity of HIV in any single person is greater than the diversity of influenza worldwide,” notes Barouch. “And the diversity of HIV worldwide is orders of magnitude greater than the diversity of influenza. If you need a new vaccine for the flu every year, then you can extrapolate the challenges for creating a vaccine for HIV.” But it is just this scientific complexity that drew Barouch into the AIDS field in the first place, where his scientific fascination with the pathogen – host interaction merged naturally with his desire to have a substantial impact on a global problem. Today his laboratory at BIDMC takes a translational approach to the search for an HIV vaccine, from basic studies looking at the underlying pathogenesis and immune response of the virus to pre-clinical investigations in animal models to human clinical trials.
Because the exact kinds of immune responses necessary for protection against HIV remain a mystery, Barouch points out that this broad-based and translational approach, which merges the empiric aspects of vaccine testing with the theoretical basic science aspects of the field, has become even more critical, particularly given the dearth of vaccine options that have been developed thus far. “One of the major challenges is that not enough vaccine candidates have been tested in clinical trials,” he says.
“One can debate whether there are not enough ideas, whether there’s not enough infrastructure, not enough funding, but the bottom line is today there have only been three vaccine concepts tested for efficacy in humans in 30 years. That’s one of the major limitations in the field —there have simply not been enough shots on goal.”
Barouch believes that more shots will come, through the unique structure of his own lab along with BIDMC’s recent move to combine two related divisions to create a new comprehensive Center for Virology and Vaccine Research after the death of HIV vaccine pioneer Norman Letvin, M.D., last May. He thinks that expanding the breadth and depth of work in this field should also augment its philanthropic appeal. While his own lab has been fortunate enough to receive substantial funding from a variety of sources, including the National Institutes of Health, the Gates Foundation, the Department of Defense, and the Ragon Institute, Barouch knows that funding fuels progress. “Philanthropic support for this kind of research is incredibly important and catalytic because it gives investigators the ability to be flexible and creative,” he says. “It also can potentially give them a good return on their investment because it might not only lead to a new vaccine or a new drug, but it also advances knowledge of human immunology that would be applicable to other diseases.”
But, of course, Barouch’s overarching goal is to bring an AIDS vaccine to fruition as quickly as possible, and in recent years his team has had good luck in bringing some novel ideas from the laboratory to the clinic. Back in January, they published a study in the journal Nature that identified promising new vaccine candidates which protected monkeys against a powerful strain of SIV, a simian virus similar in nature to HIV. Widely publicized, the study found that several experimental vaccines, which combine two different technologies to both “prime” and “boost” the immune system, reduced the chances that a monkey would be infected by a virulent strain of SIV by 80 to 83 percent, compared with a placebo. The vaccines also significantly reduced the amount of virus in the blood of monkeys that did become infected. Because the vaccines were derived from a different strain of virus than the challenge virus, the research provides scientists with a more accurate test of what might be faced under “real world” conditions, in which humans are likely to encounter viruses that are not genetically identical to those used in the vaccine. “This study is a bridge,” says Barouch, “because it evaluates, in the best preclinical model we have, a number of our leading vaccine concepts and provides the scientific basis for clinical evaluation of these concepts moving forward.”
Barouch says that this work, which demonstrates that protection appears to be possible in a stringent preclinical model, along with the recent success of one of the human vaccine efficacy trials (RV144 in Thailand) has brought about a turning point in the quest for an AIDS vaccine, which some have gone so far as calling one of the biggest challenges in modern biomedical research. “I think the combination of the preclinical advances and the clinical advances provide new optimism in the field, a new optimism that the development of an HIV vaccine appears like it is more possible now than it has ever been in the past. It now appears to be a tangible goal rather than a goal without scientific basis, and now we’ll continue our hard work to try to make it a reality.”