It will be critical to confirm the observations made with studies using the SHIV model. mechanism Troglitazone of bystander killing has remained controversial. In this Troglitazone issue, Richard et al. (2016) attribute bystander killing largely to antibodies mediating ADCC. They further suggest that a small CD4 mimetic developed by the Sodroski group might be used to alter this pathogenic mechanism for therapeutic benefit. How can the conflicting findings regarding ADCC antibodies be explained? And what caveats should be considered in using CD4 mimetics? As reported by Richard et al. in this issue of by co-culturing with the CD4 mimetic (Lee et al., 2015). The current study was conducted primarily with the A32 antibody, together with a small number of sera from HIV-infected individuals. ADCC antibodies are among the first elicited following infection, as the gp120CCD4 interaction leads to exposure of cluster Mouse monoclonal antibody to Protein Phosphatase 3 alpha A epitopes. Not all such CD4-induced epitopes elicit equivalent ADCC activities, due to subtle differences in Troglitazone antibody-epitope recognition and/or Fc differences (Gohain et al., 2015). Moreover, antibodies targeting Troglitazone other Env sites, including some with neutralizing activity such as 2G12 and b12, also mediate ADCC. The relative abundance of all these antibodies in the human sera tested was not determined. Further, the degree of gp120 shedding and levels of CD4 and Env present on the cells tested compared to uncultured, primary HIV-infected cells was not reported. It will be critical to confirm the observations made with studies using the SHIV model. Similarly, the effects of CD4 mimetic administration must be determined. It is an obvious therapeutic candidate, however, the possibility that it might facilitate greater CD4-independent infection must be considered. Vaccine-elicited ADCC antibodies recognizing cluster A epitopes might well be protective, as they target an early epitope uncovered during virus transmission. Use of the CD4 mimetic in vaccine design might also stimulate development of such ADCC-mediating antibodies. However, if incomplete protection and break-through infection occurred following administration of such a vaccine, accelerated CD4 T cell loss and disease progression might occur by the mechanism reported by Richard et al.. To circumvent this possibility, Troglitazone vaccine design should include several immune targets to achieve balanced protection against HIV infection..