Injection of antibodies against immunodominant epitopes tunes germinal centres to generate broadly neutralizing antibodies

The development of broadly neutralizing antibodies is critical for the control of many life-threatening viral infections like HIV, influenza, or hepatitis. Elite neutralizers are generated by natural germinal centre (GC) reactions in a very small subset of patients. The best strategy of how to promote the generation of broadly neutralizing antibodies is not known. Here, computer simulations of GC reactions are used to predict a feedback loop based on memory B cells from previous GC reactions that promotes GCs to focus on new epitopes. The simulations suggest that the injection of antibodies against immunodominant epitopes fosters affinity maturation of antibodies specific for rare or hidden epitopes. This principle can be used for the design and testing of future therapies and vaccination protocols.