Date: Mon, 6 Feb 1995 12:21:38 +0500
From: awilson@smtpinet.aspensys.com (Wilson, Anne)
Subject: NIAID News: Chimpanzee Vaccine Model

N E W S   R E L E A S E
*****************************
National Institutes of Health
National Institute of Allergies and Infectious Diseases
February 1, 1995


     Chimpanzee Vaccine Model Protects Against HIV-1 Infection

      Chimpanzees inoculated with one HIV-1 strain can resist later
infection with a different strain, according to scientists from the
National Institutes of Health (NIH) and two other institutions. 
Successful protection, their experiments show, depends on the
infectiousness of the first strain.
      Unlike humans, chimpanzees infected with HIV-1 fail to
develop disease.  The scientists reasoned that an initial HIV infection
might act like a weakened live-virus vaccine such as the Sabin polio
vaccine.  
      "In this study, the first infection simulated the effect of a
successful attenuated HIV-1 vaccine," says Riri Shibata, Ph.D., the
study's lead author.  "The virus induced protective immunity against
a subsequent HIV-1 infection.  Scientists now have a model system
that can help develop an attenuated HIV-1 vaccine for humans."  
      Dr. Shibata, a Fogarty visiting associate with the National
Institute of Allergy and Infectious Diseases (NIAID), part of NIH,
plans to present the study data on Wednesday, 
Feb. 1 at the Second National Conference on Human Retroviruses
and Related Infections in Washington, D. C.
      For their study, they used two chimpanzees infected three
and seven years earlier, respectively, with the laboratory-grown HIV-
1 strain IIIB.  They tried to superinfect the animals by exposing them
to multiple high doses of HIV-1-DH-12, a strain recently isolated from
an AIDS patient and known to thrive in chimpanzee cells.
      In September 1993, the scientists injected one animal with a
dose of DH-12 known to induce infection in a chimpanzee.  In the
ensuing four and a half months, they used a technique called
polymerase chain reaction (PCR), which can detect minute amounts
of virus, to determine if the DH-12 virus successfully infected the
chimpanzee.  Repeated PCR tests consistently found evidence of
IIIB but not of DH-12, suggesting that the animal was protected from
the DH-12 challenge.    
      In January 1994, the investigators gave the first chimpanzee
a second DH-12 dose 10 times larger than the first.  They also gave
the same larger dose of DH-12 to the second IIIB-infected
chimpanzee.  Multiple PCR tests and virus isolations in both animals
over the next four months were positive for IIIB but always negative
for DH-12.
      In May 1994, the researchers exposed the second
chimpanzee to another dose of DH-12 100 times larger than the first. 
They also took 10 milliliters (about two teaspoonsful) of blood from a
third chimpanzee experimentally infected with DH-12 four months
earlier and injected it into the first IIIB-infected chimpanzee to mimic
the type of exposure that occurs to an intravenous drug user.  To
date, both IIIB-infected chimpanzees show no evidence of DH-12
infection by either PCR or virus isolation techniques, Dr. Shibata
plans to report.
      Before the study, in both animals the scientists could detect
neutralizing antibodies against the IIIB strain but not against the DH-
12 strain, suggesting that cell-mediated immunity was responsible for
the protection observed.  This finding will be investigated further to
delineate what component(s) of the immune system may be
responsible for resistance to infection.
      To evaluate how potent an attenuated vaccine must be to
protect an animal from a subsequent HIV-1 infection, the scientists
recently challenged two more chimpanzees inoculated earlier with
SF2, a different HIV-1 strain.  SF2 also does not induce disease in
chimpanzees but is much weaker than IIIB, generating only very low
levels of virus in infected animals.  
      In September 1994, the scientists inoculated each of the two
SF2-infected chimpanzees with a low-dose of DH-12.  In contrast to
the experiments with the IIIB-infected animals, the two SF2-infected
animals became infected with DH-12 within four weeks of exposure. 
However, they had 35- to 50-fold less DH-12 in their blood than did
an unvaccinated chimpanzee exposed to DH-12.
      These studies show that chimpanzees can be protected from
a subsequent challenge with HIV-1, provided the animals are first
immunized with a potent attenuated live-virus vaccine.  Experiments
in progress will ascertain how the extent of virus attenuation
correlates with resistance to subsequent HIV infection.
      Dr. Shibata works as a microbiologist in NIAID's Laboratory
of Molecular Microbiology, headed by Malcolm A. Martin, M.D.,
senior author on the study.  Study collaborators include Christine
Broscius, B.S., of NIAID in Bethesda, Md.; Patrice Frost, D.V.M., and
Zimra Israel, Ph.D., of the Coulston Foundation in Almagordo, N.M.;
Thomas Matthews, Ph.D., of Duke University in Durham, N.C.; and
Larry O. Arthur, Ph.D., of the National Cancer Institute facility in
Frederick, Md.
      NIAID supports investigators and scientific studies at
universities, medical schools, hospitals and research institutions in
the United States and abroad aimed at preventing, diagnosing and
treating such illnesses as AIDS, tuberculosis and asthma as well as
allergies.  NIH is an agency of the U.S. Public Health Service, part of
the U.S. Department of Health and Human Services.

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