Human neutralizing monoclonal antibodies of the IgG1 subtype protect against mucosal simian-human immunodeficiency virus infection
Human neutralizing monoclonal antibodies of the IgG1 subtype protect against mucosal simian-human immunodeficiency virus infection
复制标题
DOI：
10.1038/72309
复制
发表时间：
2000-02-01
期刊：
影响因子：
82.9
通讯作者：
Ruprecht, RM
中科院分区：
文献类型：
--
作者：
Baba, TW;Liska, V;Ruprecht, RM
虽然母体人类免疫缺陷病毒1型（HIV-1）的传播发生在妊娠期间，分娩期间和产后（通过母乳喂养），但50-70%的受感染儿童似乎在分娩前不久或分娩期间获得HIV-1（1）。流行病学证据表明，粘膜暴露是分娩期HIV传播的一个重要方面（2，3）。已经开发了一种猴免疫缺陷病毒（SIV）猕猴模型（4），该模型模拟分娩期HIV-1传播期间可能发生的粘膜暴露。为了开发针对分娩期HIV-1传播的免疫预防，我们使用了SHIV-vpu（+）（参考文献10）。5，6），一种编码HIV-IIIB的env基因的嵌合猴-人病毒。抗HIV-1人单克隆抗体的几种组合。已经鉴定出通过协同相互作用在体外完全中和SHIV-vpu（+）（7）。在这里，我们用人IgG 1单克隆抗体F105、2G 12和2F 5的三重组合治疗了四只怀孕的猕猴。所有四只猕猴在分娩后均免受静脉注射SHIV-vpu（+）攻击。婴儿出生后接受单克隆抗体，并在此后不久口服SHIV-vpu（+）。在6个月的随访中，我们没有发现任何婴儿感染的证据。这表明IgG 1单克隆抗体可保护新生儿免受粘膜慢病毒攻击。我们的结论是，三种单克隆抗体识别的表位是实现实质性保护的重要决定因素，从而为艾滋病疫苗的开发提供了合理的依据。
Although maternal human immunodeficiency virus type 1 (HIV-1) transmission occurs during gestation, intrapartum and postpartum (by breast-feeding), 50-70% of all infected children seem to acquire HIV-1 shortly before or during delivery(1). Epidemiological evidence indicates that mucosal exposure is an important aspect of intrapartum HIV transmission(2,3). A simian immunodeficiency virus (SIV) macaque model has been developed(4) that mimics the mucosal exposure that can occur during intrapartum HIV-1 transmission. To develop immunoprophylaxis against intrapartum HIV-1 transmission, we used SHIV-vpu(+) (refs. 5,6), a chimeric simian-human virus that encodes the env gene of HIV-IIIB. Several combinations of human monoclonal antibodies against HIV-1. have been identified that neutralize SHIV-vpu(+) completely in vitro through synergistic interaction(7). Here, we treated four pregnant macaques with a triple combination of the human IgG1 monoclonal antibodies F105, 2G12 and 2F5. All four macaques were protected against intravenous SHIV-vpu(+) challenge after delivery. The infants received monoclonal antibodies after birth and were challenged orally with SHIV-vpu(+) shortly thereafter. We found no evidence of infection in any infant during 6 months of follow-up. This demonstrates that IgG1 monoclonal antibodies protect against mucosal lentivirus challenge in neonates. We conclude that epitopes recognized by the three monoclonal antibodies are important determinants for achieving substantial protection, thus providing a rational basis for AIDS vaccine development.