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Journal of Virology, March 2002, p. 2123-2130, Vol. 76, No. 5
0022-538X/02/$04.00+0     DOI: 10.1128/jvi.76.5.2123-2130.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Determination of a Statistically Valid Neutralization Titer in Plasma That Confers Protection against Simian-Human Immunodeficiency Virus Challenge following Passive Transfer of High-Titered Neutralizing Antibodies

*** Yoshiaki Nishimura,1 Tatsuhiko Igarashi,1 Nancy Haigwood,2 Reza Sadjadpour,1 Ron J. Plishka,1 Alicia Buckler-White,1 Riri Shibata,3 and Malcolm A. Martin1*

Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892,1 Seattle Biomedical Research Institute, Seattle, Washington 98109 ,2 Gilead Sciences, Foster City, California 944043

Received 5 October 2001/ Accepted 6 December 2001

We previously reported that high-titered neutralizing antibodies directed against the human immunodeficiency virus type 1 (HIV-1) envelope can block the establishment of a simian immunodeficiency virus (SIV)/HIV chimeric virus (SHIV) infection in two monkeys following passive transfer (R. Shibata et al., Nat. Med. 5:204-210, 1999). In the present study, increasing amounts of neutralizing immunoglobulin G (IgG) were administered to 15 pig-tailed macaques in order to obtain a statistically valid protective neutralization endpoint titer in plasma. Using an in vitro assay which measures complete neutralization of the challenge SHIV, we correlated the titers of neutralizing antibodies in plasma at the time of virus inoculation (which ranged from 1:3 to 1:123) with the establishment of infection in virus-challenged animals. Ten of 15 monkeys in the present experiment were virus free as a result of neutralizing IgG administration as monitored by DNA PCR (peripheral blood mononuclear cells and lymph node cells), RNA PCR (plasma), virus isolation, and the transfer of lymph node cell suspensions (108 cells) plus 8 ml of whole blood from protected animals to naïve macaques. The titer of neutralizing antibodies in the plasma calculated to protect 99% of virus-challenged monkeys was 1:38.

* Corresponding author. Mailing address: Laboratory of Molecular Microbiology, NIH, NIAID, 9000 Rockville Pike, Bldg. 4, Rm. 315, Bethesda, MD 20892. Phone: (301) 496-4012. Fax: (301) 402-0226. E-mail: malm{at}nih.gov.

Journal of Virology, March 2002, p. 2123-2130, Vol. 76, No. 5
0022-538X/02/$04.00+0     DOI: 10.1128/jvi.76.5.2123-2130.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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