Date: Mon, 6 Feb 1995 12:48:00 +0500
From: awilson@smtpinet.aspensys.com (Wilson, Anne)
Subject: NIAID News: Drug Sensitive HIV & Safer AIDS Vaccine

N E W S   R E L E A S E
*****************************
National Institutes of Health
National Institute of Allergy and Infectious Diseases
January 31, 1995


     Drug-Sensitive HIV Could Make Safer AIDS Vaccine

      Experimental vaccines based on live but weakened or
attenuated forms of HIV could be safer thanks to a drug-susceptible
HIV clone created by scientists at the National Institute of
Allergy and Infectious Diseases (NIAID).
      The clone can be eliminated from the body after use in the
vaccine, according to Stephen M. Smith, M.D., and Kuan Teh Jeang,
M.D., Ph.D., of  NIAID's Laboratory of Molecular Microbiology.
Dr. Smith plans to discuss the research Tuesday, Jan. 31, at the
Second National Conference on Human Retroviruses and Related
Infections in  Washington, D.C.
      Although attenuated live-virus vaccines have been licensed
for several other diseases, many scientists think that such a
vaccine based on HIV, which causes a fatal disease, may be too
hazardous.  HIV multiplies by inserting its genetic material into
that of its hosts' cells, raising concerns that even if crippled so
as not to cause disease,  HIV could lead to long-term,
unanticipated side effects.
      To bypass this problem, Drs. Smith and Jeang added to HIV a
foreign gene that codes for thymidine kinase (TK), a protein found
in HSV-1, the herpes virus that causes cold sores.  Cells that
produce this protein can be selectively killed by a drug called
ganciclovir.
      The scientists found that under certain laboratory
conditions, ganciclovir eliminated  cells infected with HIV-TK.
According to Dr. Smith, "This result suggests that after it has had
a chance to work,  an attenuated vaccine based on the HIV-TK clone
could similarly be eliminated by co-administration of ganciclovir,
reducing the concern about long-term adverse side effects."
      Drs. Smith and Jeang created their virus clone by replacing
nef, one of HIV's nine genes, with the foreign gene.  The resulting
HIV produced HSV-1 thymidine kinase, could infect T-cell lines and
stimulated immune cells in the blood.
      When they treated HIV-TK-infected cell cultures with
ganciclovir, the NIAID scientists found no increased cell death due
to HIV and no rise in levels of the HIV enzyme reverse
transcriptase--an indirect measure of HIV activity.  In untreated
cell cultures, however, significant cell death occurred, and levels
of reverse transcriptase rose.
      Dr. Smith says the virus inhibition may occur via the drug-
induced death of infected cells.  "By killing infected cells before
virus production occurs, ganciclovir interrupts the spreading HIV
infection without influencing uninfected cells."
      NIAID and the National Institutes of Health (NIH) Office of
AIDS Research supported the research.  NIAID, a component of NIH,
supports research on immunology, allergy and AIDS, tuberculosis and
other infectious diseases.  NIH is an agency of the U.S. Public
Health Service, U.S. Department of Health and Human Services.

                                    # # #