Munro, JamesSesterhenn, FabianGalloux, MarieVollers, Sabrina S.Csepregi, LuciaYang, CheDescamps, DelphyneBonet, JaumeFriedensohn, SimonGainza, PabloCorthésy, PatriciaChen, ManRosset, StéphaneRameix-Welti, Marie-AnneÉléouët, Jean-FrançoisReddy, Sai T.Graham, Barney S.Riffault, SabineCorreia, Bruno2019-03-222019-03-222019-03-22201910.1371/journal.pbio.3000164https://infoscience.epfl.ch/handle/20.500.14299/155669Throughout the last several decades, vaccination has been key to prevent and eradicate infectious diseases. However, many pathogens (e.g., respiratory syncytial virus [RSV], influenza, dengue, and others) have resisted vaccine development efforts, largely because of the failure to induce potent antibody responses targeting conserved epitopes. Deep profiling of human B cells often reveals potent neutralizing antibodies that emerge from natural infection, but these specificities are generally subdominant (i.e., are present in low titers). A major challenge for next-generation vaccines is to overcome established immunodominance hierarchies and focus antibody responses on crucial neutralization epitopes. Here, we show that a computationally designed epitope-focused immunogen presenting a single RSV neutralization epitope elicits superior epitope-specific responses compared to the viral fusion protein. In addition, the epitope-focused immunogen efficiently boosts antibodies targeting the palivizumab epitope, resulting in enhanced neutralization. Overall, we show that epitope-focused immunogens can boost subdominant neutralizing antibody responses in vivo and reshape established antibody hierarchies.text::journal::journal article::research article