The recently isolated second generation anti-HIV-1 bnAbs using high throughput techniques such as antigen-specific single B cell sorting, memory B cell expansion, micro neutralization assays, and recombinant techniques exhibited near pan neutralization breadth (14) and have a promising potential to be used for passive immunization and gene therapy (17–22, 55, 56). One such bnAb that has cleared the safety and efficacy studies is VRC01, which targets the conserved CD4bs on gp120 and neutralizes HIV-1 by partially mimicking the binding of CD4 to this region (13, 22). Presently, VRC01 is being tested, in a number of human trails, for its safety, pharmacokinetics, and virological impact in infants at risk of infection and in HIV-1-infected aviremic and viremia subjects (20, 57). In addition to the therapeutic potential of whole IgGs, small antibody fragments (scFvs) are being evaluated as potential reagents for their protective effect (56, 58). The scFvs, by virtue of their small size, can gain access to sterically occluded epitopes that cannot be approached by whole IgGs (59–61). One of the targets of bnAbs, the CD4 induced (CD4i) site, is only transiently exposed on conformational changes following binding of the viral envelope gp120 to the CD4 receptor on immune cells. Recently and in the previous studies, the scFvs, targeting the CD4i site, exhibited broad neutralization potential with 80–100 percent breadth against the HIV-1 viruses tested from different subtypes globally (62–64).