But given the track record, you probably wouldn't want to predict a time frame for when we could realistically see a vaccine, right?
I really think it's folly to predict a time frame when you're dealing with discovery. You just never know when you're going to discover what it is that's going to really put you on the pathway. When you're dealing with development where you know exactly what you're aiming at, as we've done with other viruses, for which we have made successful vaccines, then it's pretty easy for me to give you a time frame.
When you envision a final product, is it good enough—given all the difficulties with HIV's envelope protein—to settle for a vaccine that encourages T cells to reduce a person's viral load?
I think the T cell vaccine could have something to do with blocking acquisition. Clearly the gold standard of blocking acquisition of infection is a good neutralizing antibody response. If we don't have a good neutralizing antibody response, we will not—I can predict for you—successfully get a vaccine that prevents initial infection.
So, T cell, yes—it might influence the viral load. But, I'm more interested in T cell responses to synergize with the neutralizing antibody response to help block initial infection. So, that neutralizing antibody gets rid of a lot of the virus as it comes into the body, but the cells that do escape and get infected, the T cell immune response could eliminate those cells. I think of the T cell response and the antibody response as being synergistic very early on—not just antibody blocks infection, and if that fails then T cells later on keep you in a less progressive state of disease. That could be, but none of us are giving up on the possibility that a vaccine might actually prevent initial infection.
Is there a component to this decision to redraw the way ahead in vaccine research that's driven by budgetary concerns—becausethe NIH budget is due to remain flat?
Of course. If you want to pursue new pathways and develop new programs, have new initiatives, and you have a very flat budget, it's much more difficult to maneuver that. You have to reprioritize and reassign resources from one project to another. It's much more difficult to do that—because we have a lot of worthy projects—if you have a flat budget. If you have an increase, you can be sure that we're going to selectively give that increase to vaccine discovery. But, in the face of a flat budget, it certainly constricts and constrains the flexibility that you have to do some of the things that we're talking about.
So, if a new administration came in and increased the NIH budget, the HIV vaccine program would be at the top of the list to receive new funds—even though global spending on finding a vaccine has quadrupled to near $800 million in the last decade?
The HIV vaccine is a very high priority for NIH, for NIAID, so whenever we get new resources—and hopefully that will be soon—there certainly would be a preferential targeting of those resources to vaccine discovery and development. That doesn't mean that anything that's new will automatically go to AIDS vaccine. We have a lot of other problems we need to deal with. There's malaria, there's tuberculosis, there's a whole bunch of things. But, given the seriousness of the situation, we will selectively favor that—not to the exclusion of other things, but we certainly would selectively favor that.
In terms of the priorities you outlined in the Science article, what's the top one on that list that you would want to achieve to moving the field forward?
The highest priority is a neutralizing antibody response. That brings in everything from getting the [virus's] crystallographic structure and the confirmation of the envelope to understanding how you could scaffold the epitope [antigen surface eliciting an immune response] of that particular binding site into something that's immunogenic. That, to me, is really the highest priority.
So, you want it all?