Shibata R, Igarashi T, Haigwood N, Buckler-White A, Ogert R, Ross W, Willey R, Cho M W, Martin M A
Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Nat Med. 1999 Feb;5(2):204-10. doi: 10.1038/5568.
Virus-specific antibodies protect individuals against a wide variety of viral infections. To assess whether human immunodeficiency virus type 1 (HIV-1) envelope-specific antibodies confer resistance against primate lentivirus infections, we purified immunoglobulin (IgG) from chimpanzees infected with several different HIV-1 isolates, and used this for passive immunization of pig-tailed macaques. These monkeys were subsequently challenged intravenously with a chimeric simian-human immunodeficiency virus (SHIV) bearing an envelope glycoprotein derived form HIV-1DH12, a dual-tropic primary virus isolate. Here we show that anti-SHIV neutralizing activity, determined in vitro using an assay measuring loss of infectivity, is the absolute requirement for antibody-mediated protection in vivo. Using an assay that measures 100% neutralization, the titer in plasma for complete protection of the SHIV-challenged macaques was in the range of 1:5-1:8. The HIV-1-specific neutralizing antibodies studied are able to bind to native gp120 present on infectious virus particles. Administration of non-neutralizing anti-HIV IgG neither inhibited nor enhanced a subsequent SHIV infection.
病毒特异性抗体可保护个体抵御多种病毒感染。为评估1型人类免疫缺陷病毒（HIV-1）包膜特异性抗体是否能抵抗灵长类慢病毒感染，我们从感染了几种不同HIV-1分离株的黑猩猩体内纯化了免疫球蛋白（IgG），并用其对食蟹猴进行被动免疫。随后，这些猴子通过静脉注射携带源自HIV-1DH12（一种双嗜性原始病毒分离株）包膜糖蛋白的嵌合猿猴-人类免疫缺陷病毒（SHIV）。在此我们表明，使用测量感染性丧失的试验在体外测定的抗SHIV中和活性，是体内抗体介导保护的绝对必要条件。使用测量100%中和的试验，完全保护受SHIV攻击的猕猴所需的血浆滴度范围为1:5至1:8。所研究的HIV-1特异性中和抗体能够结合感染性病毒颗粒上存在的天然gp120。给予非中和性抗HIV IgG既不抑制也不增强随后的SHIV感染。
