title: 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.
abstract: 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 (10(8) 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.
authors.affiliation: Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9000 Rockville Pike, Bldg. 4 Rm. 315, Bethesda, MD 20892, USA.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Nishimura
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Igarashi
authors.forename: Nancy
authors.initials: N
authors.lastname: Haigwood
authors.forename: Reza
authors.initials: R
authors.lastname: Sadjadpour
authors.forename: Ron J
authors.initials: RJ
authors.lastname: Plishka
authors.forename: Alicia
authors.initials: A
authors.lastname: Buckler-White
authors.forename: Riri
authors.initials: R
authors.lastname: Shibata
authors.forename: Malcolm A
authors.initials: MA
authors.lastname: Martin
mesh_terms: D000818:Animals; D004279:DNA, Viral / Q000097:blood; D015483:HIV Antibodies / Q000008:administration & dosage / Q000097:blood* / Q000276:immunology; D015658:HIV Infections / Q000517:prevention & control* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007116:Immunization, Passive; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000097:blood / Q000276:immunology; D008254:Macaca nemestrina; D009500:Neutralization Tests; D012367:RNA, Viral / Q000097:blood; D016097:Simian Acquired Immunodeficiency Syndrome / Q000517:prevention & control* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000276:immunology*
chemical_list: D004279:DNA, Viral; D015483:HIV Antibodies; D007074:Immunoglobulin G; D012367:RNA, Viral