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Journal of Virology, August 2001, p. 7470-7480, Vol. 75, No. 16
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.16.7470-7480.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Postnatal Passive Immunization of Neonatal Macaques with a Triple Combination of Human Monoclonal Antibodies against Oral Simian-Human Immunodeficiency Virus Challenge

Regina Hofmann-Lehmann,1,2 Josef Vlasak,1 Robert A. Rasmussen,1,2 Beverly A. Smith,1,2 Timothy W. Baba,1,2,3 Vladimir Liska,1,2 Flavia Ferrantelli,1,2 David C. Montefiori,4 Harold M. McClure,5 Daniel C. Anderson,5 Bruce J. Bernacky,6 Tahir A. Rizvi,6 Russell Schmidt,6 Lori R. Hill,6 Michale E. Keeling,6 Hermann Katinger,7 Gabriela Stiegler,7 Lisa A. Cavacini,2,8 Marshall R. Posner,2,8 Ting-Chao Chou,9 Janet Andersen,10 and Ruth M. Ruprecht1,2,*

Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute,1 Department of Medicine, Harvard Medical School,2 Beth Israel-Deaconess Medical Center,8 and Harvard School of Public Health,10 Boston, Massachusetts 02115; Division of Newborn Medicine, Tufts University School of Medicine, Boston, Massachusetts 021113; Center for AIDS Research, Department of Surgery, Duke University Medical Center, Durham, North Carolina 277104; Yerkes Regional Primate Research Center, Emory University, Atlanta, Georgia 303225; University of Texas, M. D. Anderson Cancer Center, Bastrop, Texas 786026; Institute of Applied Microbiology, University of Agriculture, A-1190 Vienna, Austria7; and Molecular Pharmacology and Therapeutics Program, Memorial Sloan-Kettering Cancer Center, New York, New York 100219

Received 20 February 2001/Accepted 24 May 2001

To develop prophylaxis against mother-to-child human immunodeficiency virus (HIV) transmission, we established a simian-human immunodeficiency virus (SHIV) infection model in neonatal macaques that mimics intrapartum mucosal virus exposure (T. W. Baba et al., AIDS Res. Hum. Retroviruses 10:351-357, 1994). Using this model, neonates were protected from mucosal SHIV-vpu+ challenge by pre- and postnatal treatment with a combination of three human neutralizing monoclonal antibodies (MAbs), F105, 2G12, and 2F5 (Baba et al., Nat. Med. 6:200-206, 2000). In the present study, we used this MAb combination only postnatally, thereby significantly reducing the quantity of antibodies necessary and rendering their potential use in humans more practical. We protected two neonates with this regimen against oral SHIV-vpu+ challenge, while four untreated control animals became persistently infected. Thus, synergistic MAbs protect when used as immunoprophylaxis without the prenatal dose. We then determined in vitro the optimal MAb combination against the more pathogenic SHIV89.6P, a chimeric virus encoding env of the primary HIV89.6. Remarkably, the most potent combination included IgG1b12, which alone does not neutralize SHIV89.6P. We administered the combination of MAbs IgG1b12, 2F5, and 2G12 postnatally to four neonates. One of the four infants remained uninfected after oral challenge with SHIV89.6P, and two infants had no or a delayed CD4+ T-cell decline. In contrast, all control animals had dramatic drops in their CD4+ T cells by 2 weeks postexposure. We conclude that our triple MAb combination partially protected against mucosal challenge with the highly pathogenic SHIV89.6P. Thus, combination immunoprophylaxis with passively administered synergistic human MAbs may play a role in the clinical prevention of mother-to-infant transmission of HIV type 1.

* Corresponding author. Mailing address: Dana-Farber Cancer Institute, 44 Binney St. JFB809, Boston, MA 02115-6084. Phone: (617) 632-3719. Fax: (617) 632-3112. E-mail: ruth_ruprecht{at}dfci.harvard.edu.

Journal of Virology, August 2001, p. 7470-7480, Vol. 75, No. 16
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.16.7470-7480.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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