PDF(Pubmed)
Abstract：
Recent data suggest the importance of non-neutralizing antibodies (nnAbs) in the development of vaccines against HIV-1 because two types of nnAbs that recognize the coreceptor binding site (CoRBS) and the C1C2 region mediate antibody-dependent cellular-cytotoxicity (ADCC) against HIV-1-infected cells. However, many studies have been conducted with nnAbs obtained from subtype B-infected individuals, with few studies in patients with non-subtype B infections.
We isolated a monoclonal antibody 1E5 from a CRF02_AG-infected individual and constructed two forms of antibody with constant regions of IgG1 or IgG3. The epitope of 1E5 belongs to the C1C2 of gp120, and 1E5 binds to 27 out of 35 strains (77 %) across the subtypes. The 1E5 showed strong ADCC activity, especially in the form of IgG3 in the presence of small CD4-mimetic compounds (CD4mc) and 4E9C (anti-CoRBS antibody), but did not show any neutralizing activity even against the isolates with strong binding activities. The enhancement in the binding of A32, anti-C1C2 antibody isolated from a patient with subtype B infection, was observed in the presence of 1E5 and the combination of 1E5, A32 and 4E9C mediated a strong ADCC activity.
These results suggest that anti-C1C2 antibodies that are induced in patients with different HIV-1 subtype infections have common functional modality and may have unexpected interactions. These data may have implications for vaccine development against HIV-1.
We isolated a monoclonal antibody 1E5 from a CRF02_AG-infected individual and constructed two forms of antibody with constant regions of IgG1 or IgG3. The epitope of 1E5 belongs to the C1C2 of gp120, and 1E5 binds to 27 out of 35 strains (77 %) across the subtypes. The 1E5 showed strong ADCC activity, especially in the form of IgG3 in the presence of small CD4-mimetic compounds (CD4mc) and 4E9C (anti-CoRBS antibody), but did not show any neutralizing activity even against the isolates with strong binding activities. The enhancement in the binding of A32, anti-C1C2 antibody isolated from a patient with subtype B infection, was observed in the presence of 1E5 and the combination of 1E5, A32 and 4E9C mediated a strong ADCC activity.
These results suggest that anti-C1C2 antibodies that are induced in patients with different HIV-1 subtype infections have common functional modality and may have unexpected interactions. These data may have implications for vaccine development against HIV-1.
摘要：
最近的数据表明非中和抗体(nnAbs)在开发针对HIV-1的疫苗中的重要性,因为识别共受体结合位点(CoRBS)和C1C2区的两种类型的nnAbs介导针对HIV-1感染的细胞的抗体依赖性细胞毒性(ADCC)。然而,已经对从B亚型感染个体获得的nnAbs进行了许多研究，对非B型亚型感染患者的研究很少。
我们从CRF02_AG感染的个体中分离出单克隆抗体1E5,并构建了具有IgG1或IgG3恒定区的两种形式的抗体。1E5的表位属于gp120的C1C2,并且1E5与跨越亚型的35个菌株中的27个(77%)结合。1E5显示出较强的ADCC活性，特别是在存在小的CD4模拟化合物（CD4mc）和4E9C（抗CoRBS抗体）的情况下，以IgG3的形式，但即使对具有强结合活性的分离株也没有显示任何中和活性。从B型感染患者中分离出的抗C1C2抗体A32的结合增强，在1E5的存在下观察到,并且1E5、A32和4E9C的组合介导了强的ADCC活性。
这些结果表明，在患有不同HIV-1亚型感染的患者中诱导的抗C1C2抗体具有共同的功能形态，并且可能具有意想不到的相互作用。这些数据可能对HIV-1疫苗的开发产生影响。
我们从CRF02_AG感染的个体中分离出单克隆抗体1E5,并构建了具有IgG1或IgG3恒定区的两种形式的抗体。1E5的表位属于gp120的C1C2,并且1E5与跨越亚型的35个菌株中的27个(77%)结合。1E5显示出较强的ADCC活性，特别是在存在小的CD4模拟化合物（CD4mc）和4E9C（抗CoRBS抗体）的情况下，以IgG3的形式，但即使对具有强结合活性的分离株也没有显示任何中和活性。从B型感染患者中分离出的抗C1C2抗体A32的结合增强，在1E5的存在下观察到,并且1E5、A32和4E9C的组合介导了强的ADCC活性。
这些结果表明，在患有不同HIV-1亚型感染的患者中诱导的抗C1C2抗体具有共同的功能形态，并且可能具有意想不到的相互作用。这些数据可能对HIV-1疫苗的开发产生影响。
