Increasing the Potential of AIDS Vaccines: An amfAR Grantee Update
By Jeffrey Laurence, M.D.
December 18, 2006—One of the central frustrations of AIDS research has been the elusiveness of a vaccine that could either prevent HIV infection or slow the onset of AIDS. Some of the candidates currently being tested can elicit seemingly appropriate immune responses, but are too weak to avert infection or disease. But could they be ramped up to strengthen their activity against HIV?
Earlier this year we highlighted the work, published in February, of amfAR grantee Dr. Richard Kornbluth of the University of California, San Diego. He found that two immune proteins common to mice and humans, CD40L and GITRL, greatly increased the activity of killer T cells and antibodies directed against HIV. Killer T cells and antibodies are both known to be important in killing all viruses, both during natural infection as well as after vaccination. However, Dr. Kornbluth’s experiments were all done in mice. In the November issues of the immunology journals Clinical and Vaccine Immunology and Journal of Leukocyte Biology, Kornbluth expanded his amfAR-funded research to monkey and human cells.
The key concept is to increase the power of AIDS vaccines already being tested. Kornbluth noted that most vaccines would be improved if they could elicit stronger and more durable immune responses. He suggests using novel immune boosters or “molecular adjuvants.”
Dr. Kornbluth first reviewed three major properties molecular adjuvants could have. First, they might recruit and activate specialized types of immune cells known as dendritic cells (DC). Taking a page from the cancer vaccine literature, DC have already been shown to bolster immunity against cancer cells in animals and humans. Second, they could directly stimulate T cells capable of killing HIV-infected cells. Proteins with such creative names as “alarmins” are being tested in this regard. Finally, molecular adjuvants might remove roadblocks to vaccine activity by inhibiting either immune suppressive proteins or cells such as “T-regs” (regulatory T cells).
Experimentally, Dr. Kornbluth demonstrated that the CD40L and GITRL proteins, derived from monkeys, act on human cells in the test tube by stimulating antibody-producing B cells and inhibiting immune-suppressive T cells. The next step is to use pieces of genetic material known as plasmids, modified to produce CD40L and GITRL proteins, to immunize monkeys against the simian AIDS virus, SIV. This, Kornbluth and colleagues concluded, will be “a preliminary step for their future clinical use.”
Progress in AIDS vaccine development is frustratingly slow, but amfAR-funded scientists such as Dr. Kornbluth are bringing us closer to realizing that critical goal.
Dr. Laurence is amfAR’s Senior Scientific Consultant.