amfAR grantee Dr. Dan Barouch is director of the Center for Virology and Vaccine Research at Boston’s Beth Israel Deaconess Medical Center. In observance of HIV Vaccine Awareness Day on May 18, amfAR Vice President and Director of Research Dr. Rowena Johnston spoke to Barouch about the key challenges in vaccine development, the pursuit of vaccines to potentially cure HIV, and why we should be excited about antibodies.
The first HIV vaccine trial was 30 years ago in 1987. How close are we to developing a preventive vaccine?
Scientifically the field has advanced tremendously over the past several years. Whether these advances will result in a deployable vaccine is as yet unanswered. The recent suite of efficacy trials–including HVTN 702, the large-scale HIV vaccine trial underway in South Africa—will help answer that. We and others have plans in the pipeline for additional efficacy studies, which we hope will be launched in the coming months. But before these trials yield data, it’s not possible to know for sure how close we are.
What key questions remain to be answered?
The most important questions revolve around the extent to which different immune responses result in protection in humans. If we do see protection from infection with any of these vaccines, it will be very important to determine which immune responses are useful for protecting humans. This can only be answered in an efficacy trial.
The vaccine candidate used in the RV144 trial was judged to be modestly—a little over 30%— effective. What is the threshold we need to reach in order to say that a vaccine is effective enough for general use?
This is actually a complicated question. It depends not only on the judgment of scientists and physicians, but also regulatory agencies and individual country governmental and health agencies as well as other stakeholders. In high-risk areas, it is generally believed that a 50% effective vaccine might have an important benefit for public health, which in turn might be sufficient for endorsement by local health agencies. But it’s not possible to put a number on this across the board—it will depend on the exact conditions of the epidemic at the point in time that we get a vaccine.
Most people think of vaccines as a way to prevent an infection, but you’re pursuing vaccines, and antibodies, as a way to potentially cure HIV once a person has been infected. How would this work?
We’re hoping to harness the immune system both to prevent and to treat disease. For prevention, the goal of the vaccine would be to induce immune responses that block infection. But we might also be able to use the vaccine for treatment in people already infected with HIV to boost their existing immune responses. If an individual’s responses are boosted, there might be better control of the virus than there was before. We could give the vaccine to HIV-infected individuals while they’re on ART. If the vaccine could increase host immune responses to high enough levels, the person’s own immune system might be able to control the virus.
The objective, which we’ve not yet achieved, is for the vaccine to increase host immune responses to control the virus even after the person stops taking ART. Would this be virologic suppression or an actual cure? Certainly the ultimate goal is a cure, but that’s a much more distant goal. A functional cure, where we could control the virus in the absence of ART, might be a more achievable goal, a stepping stone as we make our way towards a cure.
Is there medical precedent for a therapeutic vaccine or passive antibodies for treatment or cure of an infectious disease?
Yes. One example is the zoster vaccine. People who are infected with varicella-zoster virus, typically as children, get chickenpox. In the absence of any further intervention, some get shingles later on, typically as adults. Older adults who get the zoster vaccine can reduce their chances of getting shingles. As for the use of antibodies, it’s a little more complicated. Only one monoclonal antibody is approved for human use against an infectious disease (RSV). But hepatitis B virus and rabies and other diseases can be treated with bulk (i.e., mixed) IgG (the antibody, immunoglobulin G). Many monoclonal antibodies have become available for rheumatologic and oncologic diseases.
Why should we be excited about antibodies to cure HIV?
To cure HIV we’ll need to have a potent way to eliminate infected cells. Antibodies are about as close to magic bullets as we have. They seek out and destroy a target with incredible potency and specificity. Experimentally, antibodies have had some of the most dramatic results in preclinical studies, and early clinical data are promising. Based on the data to date, we believe that antibody-based cure approaches are warranted for further exploration.