After years in the scientific wilderness, HIV vaccine research is finding its way. Spurred by new technologies and a better understanding of how the immune system might be tweaked to fight the virus, the once-dry pipeline is now releasing a steady trickle of vaccines into studies in real-live humans. Whether these vaccines can prevent infection remains to be seen, of course, but even if not, they may delay or prevent disease by giving T-cells a head start against HIV.

Two new tools are behind all this action. One, dubbed “naked DNA,” involves injecting (into the muscle or skin) some genetic code (DNA) that the body translates into copies of HIV proteins, which can trigger an HIV-specific immune response. Another way to deliver genetic code for making HIV proteins is to use a so-called vector. Vectors are typically genetically altered viruses that cannot replicate more than once in the body and so cannot cause disease.

  • Merck & Co. is currently the only pharmaceutical company to have an advanced program. Its candidates use both naked DNA and a modified adenovirus vector (adenovirus causes colds). These are being tested both separately and combined in a “prime-boost” -- first DNA, then the vector. The University of California at Davis has just launched a Phase I safety study in HIV-negative volunteers, but it is also being studied as a therapeutic vaccine in HIVers on HAART (call 916.734.8637).

  • Another prime-boost approach, in clinical trials in Britain and Kenya, uses naked DNA followed by a different vector, modified vaccinia virus Ankara strain (MVA). In an upcoming trial sponsored by the International AIDS Vaccine Initiative (IAVI), people who got DNA alone will be boosted with MVA (click on www.iavi.org). If immune responses look good in Phase I and II, Phase III efficacy trials will start as soon as possible -- 2004 is the best estimate.

  • The new Vaccine Research Center (VRC) at the National Institutes of Health announced in October its first clinical trial (call 866.833.5433). The vaccine uses naked DNA to make mimics of two HIV proteins, Gag and Pol. These have been modified in an attempt to strengthen the immune response, and the trial will test various doses to see whether these modifications work.

  • Tests in people are also expected soon for another DNA/MVA prime-booster developed at Emory University in Atlanta. Trials will be through the NIH’s HIV Clinical Trials Network (HVTN). (Click on www.hvtn.org.)

  • An effort by researchers at Harvard has produced a DNA vaccine with a dab of IL-2 (to boost T-cell responses) attached, due for human studies at both VRC and HVTN.

  • Also on HVTN’s list is GlaxoSmithKline’s experimental vaccine, which bucks the DNA/ vector trend by using whole proteins (more expensive to produce). In addition to trials in HIV-negative folks, Glaxo has therapeutic studies planned for next year.

Finally, at the experimental stage are a multitude of souped-up DNA vaccines and new vectors, including attenuated flu viruses, salmonella bacteria and -- no kidding! -- brewer’s yeast. Let’s hope we’re closer to a vaccine pipeline that we can raise a glass to.