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                         JeffNEWS, July 12, 1994
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Intracellular Immunization Approach Shown to 
Effectively Inhibit HIV Virus Replication 
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   Using antibodies specifically altered to target an HIV protein,
Jefferson researchers have developed a potent tool for inhibiting
replication of the HIV virus in human cells. The in vitro study,
published in the May 24 issue of Proceedings of the National Academy of
Science, found that the intracellular "vaccine" induced a state of
restricted growth in HIV cells. 

   In the study, researchers developed intracellular single-chain
antibodies specifically altered to bind to the Rev protein, a key
protein responsible for the replication of the HIV virus. The
intracellular antibodies were then introduced into human cells in vitro,
where they bound to the Rev protein and rendered the cells resistant to
HIV infection.

   "HIV is an intracellular disease, a disease of DNA,"  explained Roger
Pomerantz, MD, director of the division of infectious diseases at
Jefferson. "One reason vaccines and viral drugs do not work well against
AIDS is that they target the envelope around the virus, and the reverse
transcriptase enzyme.  This envelope changes so quickly, it's very
difficult to get a single vaccine. But the regulatory proteins within
the replicating virus don't change very much at all, they're quite
homogeneous among different strains."

   Omar Bagasra, MD, PhD, research associate professor of medicine, Duan
Lingxun, PhD, research assistant professor of medicine, and other
members of the molecular retrovirology team took antibodies that
normally work outside the cell to fight disease and cloned out the DNA
to create an antibody that works inside the cell, specifically attacking
the Rev protein.   "Instead of turning things inside out, we might call
it turning things outside in," Dr. Pomerantz said.

   In addition to being highly effective in inhibiting HIV replication,
Jefferson's anti-Rev antibody approach works against many different
strains of the virus and has the potential for using the body's own
natural immune system to fight the infection rather than introducing a
foreign protein, Dr. Pomerantz said. 

   Dr. Pomerantz urged caution in evaluating intracellular immunization
or any other approaches to finding an AIDS vaccine that works.

   "We've shown we can inhibit HIV in vitro," he said. "The question is
how to get it into the body.  One idea is to take bone marrow stem
cells, the cells that repopulate the bone marrow, inject them with these
antibodies, and have them produce cells that have now become
HIV-resistant."

   The importance of gene therapy research as a promising direction in
AIDS research was underlined by Dr. Pomerantz' recent appointment by the
National Institutes of Health as chairman of a newly formed committee on
gene therapy for HIV. The group is charged with bringing gene therapy
research findings as quickly as possible to the clinical study phase.

   "It's a large leap from bench to bedside," Dr. Pomerantz said. "It's
much easier to do things in vitro than in vivo. We hope to go to Phase I
trials within the next two years,  with FDA approval. But we still have
a long way to go."


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