Nature Medicine
5, 204 - 210 (1999)
doi:10.1038/5568
Neutralizing antibody directed against the HIV−1 envelope glycoprotein
can completely block HIV−1/SIV chimeric virus infections of macaque
monkeysRiri Shibata1, 4, Tatsuhiko Igarashi1, Nancy Haigwood2, Alicia Buckler−White3, Robert Ogert1, William Ross1, Ronald Willey1, Michael W. Cho1
& Malcolm A. Martin11
Laboratory of Molecular Microbiology, National Institute
of Allergy and Infectious Diseases, National Institutes of Health,
Bethesda, Maryland 20892, USA
2
Seattle Biomedical Research Institute, Seattle, Washington 98109, USA
3
Division of Molecular Virology and Immunology, Georgetown Medical Center, Rockville, Maryland 20852, USA
4
R.S. present address: VaxGen, 1000 Marina Boulevard, Brisbane, California 94005−1841, USA
Virus−specific antibodies protect individuals against a wide variety
of viral infections1−7. To assess whether human immunodeficiency
virus type 1 (HIV−1) envelope−specific antibodies confer resistance
against primate lentivirus infections, we purified immunoglobulin (IgG) from
chimpanzees infected with several different HIV−1 isolates, and used
this for passive immunization of pig−tailed macaques. These monkeys
were subsequently challenged intravenously with a chimeric simian−human
immunodeficiency virus (SHIV) bearing an envelope glycoprotein derived form
HIV−1DH12, a dual−tropic primary virus isolate. Here
we show that anti−SHIV neutralizing activity, determined in vitro using an assay measuring loss of infectivity, is the absolute requirement
for antibody−mediated protection in vivo. Using an assay that
measures 100% neutralization, the titer in plasma for complete protection
of the SHIV−challenged macaques was in the range of 1:5−1:8. The
HIV−1−specific neutralizing antibodies studied are able to bind
to native gp120 present on infectious virus particles. Administration of non−neutralizing
anti−HIV IgG neither inhibited nor enhanced a subsequent SHIV infection.
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