There seem to be a lot of moving goal posts with respect to the HIV vaccine. It was first promised in the late '80s. Then Bill Clinton set a goal of developing one by 2008. Here we are in 2008, and the posts are being pulled down altogether and the mission is being redefined. Is this just evidence of how complex an adversary we're dealing with in HIV?
I think all of those predictions of time frames really reflect an innocent but unintentional lack of appreciation for how unique and different HIV is. Margaret Heckler [former congresswoman (R–Mass.)], who way back when the virus was discovered, in a press conference, said we should be well into a vaccine trial within two years and maybe have a vaccine soon thereafter; and President Clinton saying the goal would be to have a vaccine in 10 years—all this was really predicated on how we look at vaccines in the standard, classical way.
But, HIV can't be tamed by classical methods?
This is the critical issue. If people understand this, they'll really get it. That is: How extraordinarily unique and different HIV is.
When you're setting out to develop a vaccine, you generally use natural infection as your model, or, put a different way, as your experiment of nature. Regardless of what microbe or virus you're dealing with—even the deadly ones like smallpox and the maiming ones like measles and polio—the majority of people, and sometimes the overwhelmingly vast majority of people, may get sick and then ultimately get better. They don't die and they don't have any lasting remnants of the infection. What happens is that the body adequately and appropriately ultimately eliminates the virus and provides you with lasting protection against subsequent challenges [from that virus].
So, if you're going to go and try to develop a vaccine for microbe X, you only need to…look at what the body's natural response is and vaccinate the person with either a modified form of the virus or a subcomponent of the virus that will elicit that same antibody response or that same cell-mediated immune response, which you are certain is associated with protection because you have many many examples of the natural infection to show that. So, you already have your road map of what you need to get to get a vaccine.
But, the body's natural response is different with HIV?
Astoundingly, of the tens of millions of people who have been infected, there's not a single documented case of someone who has established infection and ultimately eradicates the virus from the body. There are a number of people who are what we call "long-term nonprogressors"—for one reason or another, perhaps their genetic makeup, they seem to handle the virus reasonably well for a long period of time. For the overwhelming majority of people, the virus ultimately overcomes their immune system's attempts to curtail the virus. So, we are dealing with a situation where we don't even know if the body is capable of eliciting a protective immune response. And if it can, we know it's very difficult, because when you look at infected people, it is so unusual to see people with very good, broadly reacting neutralizing antibodies. So, when you go after developing a vaccine for HIV, you're in an entirely different ballpark than you are when you're trying to develop a vaccine for influenza or smallpox or polio or measles.
We as a field didn't fully appreciate that early on, as a matter of fact. That's the reason why it would be an understandable statement, though now retrospectively clearly premature, to say, "Okay, we have the virus in our hand, we are growing it, we know what it is. It should be a snap to develop a vaccine." Now we know that this just is not the case, so our challenge for the future is to do much better than what natural infection does because natural infection clearly is not successful in inducing an ultimately protective response.