Genetic similarities and differences in the anti-HIV-1 Env antibody responses between humans and rhesus macaques

We previously described a method for rapid cloning human monoclonal antibody (mAb) from memory B cell (Bmem). Here, we have put this method in practice for isolating a large panel of mAbs against HIV-1 envelope (Env) protein and have extended it as a general strategy to isolate monkey mAbs against HIV-1 Env from Bmem of a SHIV infected rhesus macaque. Ninety-six new mAbs were cloned from 5 HIV-1 infected humans, of which 64 are clonally unique Env mAbs. Thirty-five mAbs against HIV-1 Env were cloned directly from Bmem or from immortalized Env B cell lines both derived from SHIV infected rhesus macaques. Genetic analyses showed that humans and rhesus macaques can use similar VH genes for generating Abs against similar Env epitopes. For example, they both can use VH1-69, VH1-24 and VH2-70 genes for mAbs against CD4 induced (CD4i) Env epitopes, and use VH5-51 gene for V3 mAbs. However, the strong bias usage of VH1-69 gene for human CD4i Abs was not seen in rhesus macaques. In addition, the biased usage of kappa gene for anti-Env Abs in HIV-1 infected people was not seen in rhesus macaques. Instead, SHIV infected rhesus macaques tends to use lamda light chain gene to encode mAbs against the HIV-1 Env protein. This information on the similarities and differences of anti-Env Ab responses between human and rhesus macaques should help to more judiciously employ the non-human primates model to advance HIV vaccine candidates into clinical trials.