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Journal of Virology, May 1999, p. 4009-4018, Vol. 73, No. 5
Division of Retrovirology, Walter Reed Army
Institute of Research and Henry M. Jackson Foundation, Rockville,
Maryland 208501; Institute of Applied
Microbiology, University of Agriculture, Vienna,
Austria2; National Institute of
Allergy and Infectious Diseases, National Institutes of Health,
Rockville, Maryland 208523; NABI,
Boca Raton, Florida 334874; and AVANT
Immunotherapeutics, Needham, Massachusetts 02494-27255
Received 2 December 1998/Accepted 27 January 1999
The role of antibody in protection against human immunodeficiency
virus (HIV-1) has been difficult to study in animal models because most
primary HIV-1 strains do not infect nonhuman primates. Using a chimeric
simian/human immunodeficiency virus (SHIV) based on the envelope of a
primary isolate (HIV-89.6), we performed passive-transfer experiments
in rhesus macaques to study the role of anti-envelope antibodies in
protection. Based on prior in vitro data showing neutralization synergy
by antibody combinations, we evaluated HIV immune globulin (HIVIG), and
human monoclonal antibodies (MAbs) 2F5 and 2G12 given alone, compared
with the double combination 2F5/2G12 and the triple combination
HIVIG/2F5/2G12. Antibodies were administered 24 h prior to
intravenous challenge with the pathogenic SHIV-89.6PD. Six control
monkeys displayed high plasma viremia, rapid CD4+-cell
decline, and clinical AIDS within 14 weeks. Of six animals given
HIVIG/2F5/2G12, three were completely protected; the remaining three
animals became SHIV infected but displayed reduced plasma viremia and
near normal CD4+-cell counts. One of three monkeys given
2F5/2G12 exhibited only transient evidence of infection; the other two
had marked reductions in viral load. All monkeys that received HIVIG,
2F5, or 2G12 alone became infected and developed high-level plasma
viremia. However, compared to controls, monkeys that received HIVIG or
MAb 2G12 displayed a less profound drop in CD4+ T cells and
a more benign clinical course. These data indicate a general
correlation between in vitro neutralization and protection and suggest
that a vaccine that elicits neutralizing antibody should have a
protective effect against HIV-1 infection or disease.
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Protection of Macaques against Pathogenic
Simian/Human Immunodeficiency Virus 89.6PD by Passive Transfer of
Neutralizing Antibodies
*
Corresponding author. Mailing address: Division of
Retrovirology, Walter Reed Army Institute of Research, 1 Taft Court,
Suite 250, Rockville, MD 20850. Phone: (301) 294-1888. Fax: (301)
294-1898. E-mail: jmascola{at}hiv.hjf.org.
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