Neutralization of Virus Infectivity by Antibodies: Old Problems in New Perspectives

Figure 3

The kinetics of NAb binding. Soluble envelope glycoprotein oligomers can be immobilized on SPR chips via His or epitope tags. If the trimers are good structural mimics of native functional oligomers, and the density of trimers approximate that on the virion surface, then the NAb binding involved in neutralization can be simulated and its kinetic constants can be determined by SPR. Here, a soluble, stabilized trimer of the envelope glycoprotein of a Clade A isolate of HIV-1 was studied. The subunits of the trimer are labeled in the schematic to the lower right; the black bars represent engineered disulfide bonds that were introduced to stabilize each protomer of the trimer. The trimer was immobilized and the binding of NAbs and non-NAbs was compared. The sensorgrams show the response (RU) over time (s) during an association phase (upward curve) and a dissociation phase (downward curve: in several cases dissociation is very slow and barely measurable). Antibodies directed to different groups of epitopes, as indicated for the three diagrams, are compared. The nonneutralizing antibodies are marked with arrows. Thus, neutralization correlates eminently with binding to trimers that are native-like according to electron microscopy. The figure is reproduced from Sanders et al. [103] with modifications.