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Settling into the New Groove: AIDS Vaccine Research 2002

By Bill Snow

Bill Snow has been one of the most vocal AIDS vaccine advocates in the US for over a decade. During this time he has served on the CAB at San Francisco's vaccine trial site (now part of the HVTN), as a member of NIH's AIDS Vaccine Research Committee (the "Baltimore" committee) and on various national AIDS vaccine policy groups. He was also a co-founder of AVAC in 1995 and is an Emeritus Member of its Board of Directors. As an openly HIV-positive man, Snow has also played a pivotal role in engaging the broader AIDS community in the search for a vaccine.

This article is reprinted, in slightly revised form, from the first issue of AVAC's new newsletter. The full AVAC Update can be viewed at www.avac.org

1994 was a watershed year for AIDS vaccine research. That year, without hard proof, envelope-based vaccines were determined inadequate to prevent HIV infection. The long-term fallout was substantial. Genentech left the business while Vaxgen picked it up. Chiron began a long re-tooling. Canarypox-based (ALVAC) vaccines became ascendant for clinical trials. IAVI came into being. NIH moved into financing product development. So the field settled into a second groove—testing various permutations of ALVAC, making other clinical material with government support, running the first efficacy trials...And eight years flew by.

As others have pointed out, 2002 looks a lot like 1994. Again, without hard proof, one efficacy trial of the last decade's approach was cancelled (ALVAC with or without a gp120 boost) and one will begin in Thailand (ALVAC + gp120). DNA and adenovirus have captured the spotlight while preparation still continues for a wider variety of Phase I trials to see where we stand with vaccine design. It seems prudent to ask now where we will be when this song winds down, many years from now. Already, some big unanswered questions—how to induce neutralizing antibody and deal with viral escape and diversity—are making people uncomfortable.

At this rate the epidemic will be devouring new regions by the time we get a vaccine, costing the human race significant productivity and self-respect. The whole AIDS experience is beginning to look like proof of the 200-year-old Malthusian theory that population outruns resources. Or like the start of a painful demonstration of how viruses and humans, through long and destructive evolutionary processes may ultimately learn to coexist: by killing the weak, poor and unlucky—for more generations than mankind will care to count.

So, what else can be done? Everyone in AIDS vaccines is working flat-out hard and every little step is excruciatingly slow and difficult. We need some answers. We could use a breakthrough. We need a bigger, better plan.

Probably the biggest questions have to do with tethering free-floating research to the real world:

What do the assays we have actually mean clinically, if anything?
How do animal studies relate to human studies, if at all?
How do we prioritize our activities, or can we?
Is there any way we can jump some cycles or speed things up?

These are difficult, humbling questions to ask, let alone try to answer. So everyone is doing his own thing, head down, nose to grindstone. With all energies focused on designing each idea of the best antigen, or developing an existing approach, or solving the riddles the virus presents us with, we very well may never get anywhere in any of our lifetimes. And half a billion dollars a year could be spent, ad nauseam, as Rome continues to burn. As Maurice Hilleman once illustrated it, the same mice are eating an ever-bigger piece of cheese.

Breakthroughs are, by definition, unpredictable and serendipitous. Fertilizing that field is the specialty of NIH and others—funding grants that are deemed worthy by peer review, not keeping too-close tabs on the work, and facilitating cross-communication. Like democracy, it's the best bad system we've got.

In the meantime, that leaves us with virtually no collective, systematic strategy—discussing what could happen across programs, planning ahead for all contingencies, setting priorities and taking risky action with the best knowledge available. Such coordinated effort doesn't suit independent-minded scientists or multiple-research networks. Like any battle plan, it will go awry. It's a great deal of work and difficulty making decisions—but at least it's not 100% dependent upon individuals and chance. When you're at sea, looking out to the horizon is a scary but essential business. So, here's a modest proposal:

Set broader goals for government-funded research. Think about designing research programs to try to tentatively answer those big, real-world questions above.
Design immunogens and trials to explore vaccine design questions. Do this, rather than vetting isolated products as each exits the Phase I/II obstacle course.
Encourage industry to cooperate (a bit). Explore information-sharing, patent-pooling and intellectual property agreements that reduce the risk to most and share some benefit with all from shared intellectual property and know-how.
Engage the world. Make some public commitments that are congruent with the seriousness of the epidemic. Take that risk.

The vaccine programs are led by some of the most talented and dedicated scientists in the world: Anthony Fauci (NIAID), Seth Berkley (IAVI), Larry Corey (HVTN), Debbie Birx (US Army), Peggy Johnston (NIAID), Gary Nabel (Vaccine Research Center). You have to admire every one of them and the dedicated public and private teams developing each vaccine candidate. But the outlook is not good because we've settled into a familiar, easy and well-worn groove. If the people working on AIDS vaccines don't shake this up, there's no other constituency to do so.