Ruprecht Ruth M, Ferrantelli Flavia, Kitabwalla Moiz, Xu Weidong, McClure Harold M
Dana-Farber Cancer Institute and Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
Vaccine. 2003 Jul 28;21(24):3370-3. doi: 10.1016/s0264-410x(03)00335-9.
We have established models for intrapartum and milk-borne HIV transmission by orally challenging neonatal macaques with chimeric simian-human immunodeficiency viruses (SHIVs). This allowed us to test safety and efficacy of passive immunization with human neutralizing monoclonal antibodies (nmAbs), which had been isolated from HIV clade B-infected individuals and which target conserved, functionally important epitopes. The nmAbs studied were F105 or IgG1b12, b12 for short (directed against the CD4 binding site), 2G12 (anti-gp120), 2F5 and 4E10 (both anti-gp41). Out of 16 newborn macaques challenged orally with different SHIV strains, 11 were completely protected by triple or quadruple nmAb combinations, even by post-exposure prophylaxis. In vitro, the combination of b12, 2G12, 2F5 and 4E10 potently neutralized primary HIV isolates of clades A, B, C, and D. Our data suggest that passive immunization with currently available anti-HIV clade B nmAbs could play a role in preventing transmission of non-clade B isolates through breastfeeding. We furthermore conclude that the epitopes recognized by the nmAbs in our successful passive immunization studies are important determinants for protection and provide targets for developing neutralizing antibody-response-based, active AIDS vaccines.
我们通过用嵌合猿猴-人类免疫缺陷病毒（SHIV）经口感染新生猕猴，建立了分娩期和母乳传播HIV的模型。这使我们能够测试从感染HIV B亚型的个体中分离出的、靶向保守的、具有功能重要性表位的人源中和单克隆抗体（nmAb）进行被动免疫的安全性和有效性。所研究的nmAb为F105或IgG1b12（简称为b12，针对CD4结合位点）、2G12（抗gp120）、2F5和4E10（均抗gp41）。在16只经口感染不同SHIV毒株的新生猕猴中，11只通过三联或四联nmAb组合得到了完全保护，即使是在暴露后预防的情况下。在体外，b12、2G12、2F5和4E10的组合能有效中和A、B、C和D亚型的原发性HIV分离株。我们的数据表明，用目前可用的抗HIV B亚型nmAb进行被动免疫可能在预防非B亚型分离株通过母乳喂养传播方面发挥作用。我们还得出结论，在我们成功的被动免疫研究中nmAb识别的表位是保护的重要决定因素，并为开发基于中和抗体反应的活性艾滋病疫苗提供了靶点。
