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multiple receptors for chemokines. These molecules are secreted by tissues after injury
and invasion by microorganisms to attract a number of white blood cells, which limits
the spread of the infection by mobilizing the body's immune defenses. Dr. Ruprecht
suggests that modulation of these systems could increase the effectiveness of DNA
vaccines. She will study chemokines and dendritic cells in HIV DNA vaccination
experiments to be done in both the test tube and in animal models.
* Leonidas Stamatatos, Ph.D., Aaron Diamond AIDS Research Center, New York,
NY, $75,000. Currently, one of the most difficult aspects in the development of
protective anti-HIV immune responses is the lack of knowledge on how best to present
HIV antigens to relevant cells of the immune system so as to induce an optimal immune
response. The generation of strong and effective immune responses against the HIV
envelope, the part of the virus that attaches to cells, may depend not only on the
structure of the viral protein used, but also on the form in which it is administered. Dr.
Stamatatos proposes to use an immunogene, a form of the HIV envelope whose structure
more closely resembles that of envelope antigens present on the surface of HIV virions
and on HIV-infected cells. He will monitor the generation of binding and neutralizing
antibodies both in the blood and the vaginal mucosa of monkeys. These studies will
provide important information regarding antigen presentation, as well as the development
of protective immune responses against HIV, and they will assist in the design of an
effective anti-HIV vaccine.
The grant recipients in immune reconstitution are:
* Aftab A. Ansari, Ph.D., Emory University, Atlanta, GA, $139,983. Dr. Ansari has
found that if CD4+ T cells from monkeys are purified and cultured with specific cellstimulating antibodies, they not only grow rapidly, but they also become resistant to the
monkey AIDS virus, SIV. Dr. Ansari proposes to obtain large numbers of white blood
cells from monkeys prior to SIV infection and freeze them. The monkeys will then be
infected with SIV and treated with a combination of antiretroviral drugs similar to that
given to HIV-infected patients. The CD4+ T cells collected earlier from these monkeys
will then be purified, expanded in cult,:re --nd rendered resistant to SIV infection through
the addition of cell-stimulating antibodies to the culture. These CD4+ T cells will theni
be given back to each monkey intravenously, and the ability of such infusions to return
the immune status of these monkeys to normal and to reduce the total amount of virus
in their blood will be studied.
* Miles W. Cloyd, Ph.D., University of Texas Medical Branch at Galveston,
Galveston, TX, $75,000. HIV decreases the number of circulating CD4+ T cells by
causing them to "home" or move into lymph nodes where many will die by integrinmediated apoptosis (programmed cell death). Dr. Cloyd believes the process starts with
the binding of HIV to two types of resting T cells - naive and memory T cells.
Antiviral therapy causes mostly memory T cells to return to circulation, because the
naive T cells continue to move into the lymph nodes as a natural process. Dr. Cloyd
seeks to understand how HIV causes this abnormal cellular distribution. Specifically, he
hopes to see if stimulation of the production of proteins that usually work in conjunction