TY - JOUR T1 - Boosting subdominant neutralizing antibody responses with a computationally designed epitope-focused immunogen JF - bioRxiv DO - 10.1101/430157 SP - 430157 AU - F Sesterhenn AU - M Galloux AU - SS Vollers AU - L Csepregi AU - C Yang AU - D Descamps AU - J Bonet AU - S Friedensohn AU - P Gainza AU - P Corthésy AU - M Chen AU - S Rosset AU - MA Rameix-Welti AU - JF Eléouët AU - ST Reddy AU - BS Graham AU - S Riffault AU - BE Correia Y1 - 2018/01/01 UR - http://biorxiv.org/content/early/2018/11/22/430157.abstract N2 - Throughout the last 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 due to 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. ER -