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Journal of Virology, May 1999, p. 4009-4018, Vol. 73, No. 5
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

John R. Mascola,1,* Mark G. Lewis,1 Gabriela Stiegler,2 Dawn Harris,1 Thomas C. VanCott,1 Deborah Hayes,1 Mark K. Louder,1 Charles R. Brown,3 Christine V. Sapan,4 Sarah S. Frankel,1 Yichen Lu,5 Merlin L. Robb,1 Hermann Katinger,2 and Deborah L. Birx1

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.

* 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.

Journal of Virology, May 1999, p. 4009-4018, Vol. 73, No. 5
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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Copyright © 1999 by the American Society for Microbiology. All rights reserved.