Alan McCord

At the August 4 session, Vaccines and Microbicides: Where Do We Go from Here?, several panelists expressed their dogged resolve to continue HIV vaccine research. This comes after a mixed bag of advances and setbacks in prevention. On the positive side, male circumcision is now shown to prevent transmission. On the negative, most of the microbicides in study have failed and two major vaccine studies were recently cancelled.

After these recent setbacks, it was somewhat surprising that the message from the panel was a united front of optimism and due-diligence in finding a vaccine — or even several — that will ultimately prevent HIV infection. Though the message was littered with the word failure, the panelists spun it with tenacity ... in order to get beyond this blip in vaccine research, learn from those failures, and steadfastly plan and manage a truly effective global agenda.

The panel referred often enough to the integration of a more vigorous research agenda, the influ­ential knowledge that comes from research “failures”, and the implementation of short-, medium- and long-term strategies. These are not new concepts, but the message is now being delivered with the tenor of an army of activists. Hovever, if it is to work, then their task now is not only to follow through with the science but also communicate to and educate the public — not to mention an increasingly skeptical group of scientists and policymakers — on what’s needed for the agenda to succeed.

Science is rarely a straight line. Indeed, most research relies heavily on what is learned from failures along the road to success. “Making new vaccines is one of the most difficult of human endeavors,” stated Tachi Yamada, the new executive director of the Gates Foundation. “Only one in ten candidates succeeds.” Yet, each of those failures informs the next stages of research. The panelists shared how researchers have hunkered down and strategically digested their learned lessons.

How have these failures influenced the outlook for a feasible vaccine? Many panelists acknowledged that we have to learn a great deal more about the fundamental basis of the human immune response. One of the fundamental obstacles to developing an effective vaccine against HIV is that nobody knows what kind of immune response, if any, is necessary and sufficient to block HIV infection — or as scientists call it the correlates of immunity. Then, with that, only look at the best candidates for success since not every product can be studied. A telling comment came midway through the session: “We need to move away from our home run mentality.”

Innovation was mentioned often ... in collecting unique vaccine ideas, in attracting and retaining bright young researchers to the field, and in converging massive venture capital with new scientific ideas. (Most Nobel science laureates received their prizes for work they started before they turned 35.) Industry must also scale up its involvement, since pharma and biotech companies currently contribute only 10% of the total investment in preventive vaccine research. Together, all of these have the potential to broaden the global vaccine agenda and fashion a true cure for HIV.

More specifically, the panelists detailed several ideas. Produce invigorated preparations for studies, all the way back to the initial pharmacokinetics, study designs and toxicity acceptance levels. Perhaps reduce rather than increase the immune response. Promote more rather than fewer mutations. Focus research on those unique situations found in HIV, such as on long-term non-progressors.

The panel also clearly stated that educating the public must be a distinct component for engaging a successful agenda. This includes building effective affiliations with media. All told, there’s a clear need for enormous resources, including a vast network of partners and ideas. As Susan Buchbinder remarked, “We cannot underestimate the value of our volunteers and the community.”

The past few years have seen a series of setbacks for both vaccine and microbicide development. These have led to a good deal of soul-searching within the scientific, activist and even funding communities. The recent decision to cancel the PAVE 100 study, and instead look toward smaller proof-of-concept studies, reflects both the realization that the current approaches to vaccines have little chance at success, along with the need to move the science forward.

Should this renewed hope actually work, only time will tell. The coming year will be one of hope and scrutiny for the global vaccine agenda. Many look to the vast expertise that’s available in the scientific world to produce a viable vaccine, yet in the same breath may wait to exhale for signs that this rehabilitated call to action will work.

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