Nature Medicine
6, 200 - 206 (2000)
doi:10.1038/72309
Human neutralizing monoclonal antibodies of the IgG1 subtype protect
against mucosal simian−human immunodeficiency virus infectionTimothy W. Baba1, 2, 3, Vladimir Liska1, 2, Regina Hofmann-Lehmann1, 2, Josef Vlasak1, 2, Weidong Xu1, 2, Seyoum Ayehunie1, 2, 11, Lisa A. Cavacini2, 4, Marshall R. Posner2, 4, Hermann Katinger5, Gabriela Stiegler5, Bruce J. Bernacky6, Tahir A. Rizvi6, Russell Schmidt6, Lori R. Hill6, Michale E. Keeling6, Yichen Lu7, Joel E. Wright8, 9, Ting-Chao Chou10
& Ruth M. Ruprecht1, 21
Department of Cancer Immonology and AIDS, Dana-Farber
Cancer Institute, Boston, Massachusetts 02115
, USA
8
Department of Adult Oncology, Dana-Farber Cancer Institute
, Boston, Massachusetts 02115,
USA
2
Department of Medicine, Harvard Medical School,
Boston, Massachusetts 02115, USA
9
Department of Biological Chemistry and Molecular Pharmacology,
Harvard Medical School, Boston, Massachusetts
02115, USA
3
Division of Newborn Medicine, Department of Pediatrics,
Tufts University School of Medicine, Boston, Massachusetts
02111, USA
4
Beth Israel-Deaconess Medical Center, Boston
, Massachusetts 02215, USA
5
Institute of Applied Microbiology, A-1190
Vienna, Austria
6
Department of Veterinary Sciences, University of Texas,
M.D. Anderson Cancer Center, Bastrop, Texas
78602, USA
7
Harvard School of Public Health, Boston
, Massachusetts 02115, USA
10
Laboratory of Biochemical Pharmacology and Preclinical
Pharmacology Core Facility, Memorial Sloan-Kettering Cancer Center,
New York, New York 10021, USA
11
S.A. present address: MatTek Corporation,
Ashland, Massachusetts 01721, USA
Correspondence should be addressed to Ruth M. Ruprecht ruth_ruprecht@dfci.harvard.eduAlthough maternal human immunodeficiency virus type 1 (HIV-1) transmission
occurs during gestation, intrapartum and postpartum (by breast-feeding), 50−70%
of all infected children seem to acquire HIV-1 shortly before or during delivery1. Epidemiological evidence indicates that mucosal exposure is an
important aspect of intrapartum HIV transmission2,
3. A simian
immunodeficiency virus (SIV) macaque model has been developed4
that mimics the mucosal exposure that can occur during intrapartum HIV-1 transmission.
To develop immunoprophylaxis against intrapartum HIV-1 transmission, we used
SHIV−vpu+ (refs. 5,6), a chimeric simian−human virus that encodes the
env gene of HIV-IIIB. Several combinations of human monoclonal antibodies
against HIV-1 have been identified that neutralize SHIV−vpu+
completely in vitro through synergistic interaction7.
Here, we treated four pregnant macaques with a triple combination of the human
IgG1 monoclonal antibodies F105, 2G12 and 2F5. All four macaques were protected
against intravenous SHIV−vpu+ challenge after delivery.
The infants received monoclonal antibodies after birth and were challenged
orally with SHIV−vpu+ shortly thereafter. We found no
evidence of infection in any infant during 6 months of follow-up. This demonstrates
that IgG1 monoclonal antibodies protect against mucosal lentivirus challenge
in neonates. We conclude that epitopes recognized by the three monoclonal
antibodies are important determinants for achieving substantial protection,
thus providing a rational basis for AIDS vaccine development.
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