Hints how broadly neutralizing antibodies arise (paper here). (Haynes lab here) Antibodies can be developed to bind virtually any antigen. There is a stark difference however between the ‘binding’ antibodies and ‘neutralizing’ antibodies. Binding antibodies are those that make contact with the antigen and perhaps flag it for elimination. This is in contrast to neutralizing antibodies, whose binding eliminates the biological activity of the antigen. A special class of such neutralizing antibodies are ‘broad neutralizing antibodies’. These are molecules which are capable of neutralizing multiple strains of the antigen. Such broadly neutralizing antibodies are very important in the fight against highly malleable diseases such as Influenza or HIV.

The process how such antibodies arise is still poorly understood. In the manuscript of Williams et al., they make a link between the memory and plasma B cells of broadly neutralizing antibodies and find their common ancestor. The common ancestor turned out to be auto-reactive, which might suggest that some degree of tolerance is necessary to allow for broadly neutralizing abs (‘hit a lot of targets fatally’). From a more engineering perspective, they create chimeras of the plasma and memory b cells and demonstrate that they are much more powerful in neutralizing HIV.

Ineresting data: their crystal structures are different broadly neutralizing abs co-crystallized with the same antigen (altought small…). Good set for ab-specific docking or epitope prediction — beyond the other case like that in the PDB (lysozyme)! At the time of writing the structures were still on hold in the PDB so watch this space…