Requiem for a Vaccine

Several articles that appeared in early April in the scientific press signaled the end of a research era of sorts, if they didn't constitute a downright obituary for it. After more than 20 years of searching, the AIDS research community is raising something of a white flag on the search for a prophylactic vaccine. They didn't quite say it that way, and they're not really giving up, but following the failure last fall of a clinical trial conducted by Merck &Co. (Whitehouse Station, NJ) on a vaccine for which the community held high hopes, leading AIDS scientists are urging their colleagues to go back to the drawing board. That is, they're calling for the community to spend less money on product development and more on basic research.

Michelle Hoffman

Of course, researchers have worked for a long time on other disease conditions—cancer comes most readily to mind—and have not produced a prophylactic vaccine or a cure. The difference is that cancer is a term that applies to any number of diseases, which affect many different organs and cell types. In addition, many endogenous and/or environmental factors contribute to cancer's onset and progression. HIV, on the other hand, is the only agent that causes AIDS. It has a finite number of genes and proteins, most of which have been studied in exquisite detail since the virus was first linked to the disease about 25 years ago. So, I'm wondering what researchers expect to find when they go back to basic research that they haven't found before?

In spite of this seeming impasse, I have to remark on the incredible creativity that has gone into AIDS research. Scientists tried strategies that, although they did not work with AIDS, will and have undoubtedly advanced vaccine protocols for other diseases. AIDS research also accelerated the pace of molecular biological development beyond what it might otherwise have been in less urgent circumstances.

Nevertheless, HIV is a formidable and slippery foe, slippery because of what seems an almost dastardly ability to mutate to resist or elude any prophylactic trap set for it.

In an editorial appearing in the April 3, 2008, issue of Nature, the journal's editor writes that the AIDS vaccine "crisis" is one of the field's own making. The AIDS vaccine research community has fairly consistently made promises it could not keep. The Nature editorial cautions that other disciplines are also susceptible to hype and oversell, offering the examples of stem-cell research, Parkinson's disease, and autism. To that list I would add gene therapy and siRNA (small interfering RNA).

I agree that many of these technologies get pushed prematurely into the clinic and then wither because of both waning scientific interest and investment interest. But I would offer an additional lesson from the AIDS vaccine situation: Beware of anyone who claims that a new biotechnology is going to produce an imminent cure. These technologies are powerful and will someday produce fabulous benefits, but probably not immediately. Those in the investment community need to likewise learn the value of long-term investing. Forcing promising technologies into the clinic too early almost always dooms them—at least temporarily. Remember that monoclonal antibodies are only now realizing the promise they held some 30 years after they were developed.

There's one more lesson to learn from the so-called AIDS vaccine crisis. In an article in the April 4, 2008, issue of Science, the AIDS research community acknowledged that the Rhesus macaque monkey model now used to test potential vaccines isn't working well and agreed that they need to find a more predictive animal model. That makes a lot of sense. Having the right animal model, it seems to me, is key to finding effective therapies for just about everything. The question I have is that after using this model for about 20 years, why are they just now questioning its validity?

The good news with AIDS is, as it's always been, that the vast majority of cases can be prevented by human caution and vigilance. That's also the bad news.

Michelle Hoffman is editor-in-chief of Pharmaceutical Technology. Send your thoughts and story ideas to her via email, at mhoffman@advanstar.com