Ramirez Valdez Kristel Paola, Kuwata Takeo, Maruta Yasuhiro, Tanaka Kazuki, Alam Muntasir, Yoshimura Kazuhisa, Matsushita Shuzo
Matsushita Project Laboratory, Center for AIDS Research, Kumamoto University, Kumamoto, Japan.
Matsushita Project Laboratory, Center for AIDS Research, Kumamoto University, Kumamoto, Japan; AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan.
Virology. 2015 Jan 15;475:187-203. doi: 10.1016/j.virol.2014.11.011. Epub 2014 Dec 5.
Antibodies with modest neutralizing activity and narrow breadth are commonly elicited in HIV-1. Here, we evaluated the complementary and synergistic activities of a set of monoclonal antibodies (MAb) isolated from a single patient, directed to V3, CD4 binding site (CD4bs), and CD4 induced (CD4i) epitopes. Despite low somatic hypermutation percentages in the variable regions, these MAbs covered viral strains from subtypes B, C, A and CRF01_AE and transmitted/founder viruses in terms of binding, neutralizing and antibody-dependent cell-mediated cytotoxicity (ADCC) activities. In addition, a combination of the anti-V3 and CD4bs MAbs showed a synergistic effect over the neutralization of HIV-1JR-FL. A humoral response from a single patient covered a wide range of viruses by complementary and synergistic activities of antibodies with different specificities. Inducing a set of narrow neutralizing antibodies, easier to induce than the broadly neutralizing antibodies, could be a strategy for developing an effective vaccine against HIV-1.
在HIV-1感染中通常会产生具有适度中和活性且广度较窄的抗体。在此，我们评估了从一名患者中分离出的一组针对V3、CD4结合位点（CD4bs）和CD4诱导（CD4i）表位的单克隆抗体（MAb）的互补和协同活性。尽管可变区的体细胞超突变百分比很低，但这些单克隆抗体在结合、中和及抗体依赖性细胞介导的细胞毒性（ADCC）活性方面覆盖了B、C、A和CRF01_AE亚型的病毒株以及传播/奠基者病毒。此外，抗V3和CD4bs单克隆抗体的组合对HIV-1JR-FL的中和显示出协同效应。单一患者的体液反应通过具有不同特异性的抗体的互补和协同活性覆盖了广泛的病毒。诱导一组比广泛中和抗体更容易诱导的窄中和抗体，可能是开发针对HIV-1的有效疫苗的一种策略。
