Epitope specificities of broadly neutralizing plasmas from HIV-1 infected subjects

The characterization of the cross-reactive, or heterologous, neutralizing antibody (NAb) responses developed during HIV-1-infection is relevant to the development of an HIV vaccine. Here we summarize our recently published study where we characterized the cross-reactive NAb responses in two cohorts of anti-retroviral naïve, healthy, acute and chronically HIV-infected subjects (N = 39) and present new information regarding epitope specificities. We determined that anti-CD4-binding site antibodies are responsible for the exceptionally broad cross-neutralizing antibody responses recorded only in rare plasma samples. Plasma from three subjects with moderate to high breadth of heterologous neutralizing antibody responses contained antibodies targeting the 4E10-epitope within the gp41 transmembrane subunit, and plasma from one these three subjects also contained antibodies against the 2F5 epitope. However, In most subjects with moderate to high breadth of cross-neutralization, the specificities of their NAb responses remain unknown. Overall, our study indicates that more than one pathway leads to the development of broad cross-reactive NAbs during HIV-infection.