Nature Medicine
6, 207 - 210 (2000)
doi:10.1038/72318
Protection of macaques against vaginal transmission of a pathogenic HIV-1/SIV
chimeric virus by passive infusion of neutralizing antibodiesJohn R. Mascola1, 2, Gabriela Stiegler3, Thomas C. VanCott1, Hermann Katinger3, Calvin B. Carpenter4, Chris E. Hanson4, Holly Beary1, Deborah Hayes1, Sarah S. Frankel1, Deborah L. Birx1
& Mark G. Lewis11
Division of Retrovirology, Walter Reed Army Institute
of Research and Henry M. Jackson Foundation, 1 Taft Court, Suite
250, Rockville, Maryland 20850,
USA
2
Department of Infectious Diseases, Naval Medical Research
Center, Forrest Glenn, Maryland 20910,
USA
3
Institute of Applied Microbiology, University of Agriculture
, Vienna, Austria
4
Division of Veterinary Medicine, Walter Reed Army Institute
of Research, Forrest Glenn, Maryland 20910
, USA
Correspondence should be addressed to John R. Mascola jmascola@hiv.hjf.orgThe development of the human immunodeficiency virus-1 (HIV-1)/simian immunodeficiency
virus (SIV) chimeric virus macaque model (SHIV) permits the in vivo
evaluation of anti-HIV-1 envelope glycoprotein immune responses1,
2,
3.
Using this model, others, and we have shown that passively infused antibody
can protect against an intravenous challenge4,
5. However, HIV-1
is most often transmitted across mucosal surfaces6,
7,
8,
9
and the intravenous challenge model may not accurately predict the role of
antibody in protection against mucosal exposure. After controlling the macaque
estrous cycle with progesterone10, anti-HIV-1 neutralizing monoclonal
antibodies 2F5 and 2G12, and HIV immune globulin were tested11,
12,
13.
Whereas all five control monkeys displayed high plasma viremia and rapid CD4
cell decline, 14 antibody-treated macaques were either completely protected
against infection or against pathogenic manifestations of SHIV-infection.
Infusion of all three antibodies together provided the greatest amount of
protection, but a single monoclonal antibody, with modest virus neutralizing
activity, was also protective. Compared with our previous intravenous challenge
study with the same virus and antibodies5, the data indicated
that greater protection was achieved after vaginal challenge. This study demonstrates
that antibodies can affect transmission and subsequent disease course after
vaginal SHIV-challenge; the data begin to define the type of antibody response
that could play a role in protection against mucosal transmission of HIV-1.
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