%0 Journal Article
%T Boosting subdominant neutralizing antibody responses with a computationally designed epitope-focused immunogen
%A Barney S. Graham
%A Bruno E. Correia
%A Che Yang
%A Delphyne Descamps
%A Fabian Sesterhenn
%A Jaume Bonet
%A Jean-Fran£¿ois ¨¦l¨¦ou£¿t
%A Lucia Csepregi
%A Man Chen
%A Marie Galloux
%A Marie-Anne Rameix-Welti
%A Pablo Gainza
%A Patricia Corth¨¦sy
%A Sabine Riffault
%A Sabrina S. Vollers
%A Sai T. Reddy
%A Simon Friedensohn
%A St¨¦phane Rosset
%J -
%D 2019
%R 10.1371/journal.pbio.3000164
%X Throughout 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
%K Antibodies
%K Enzyme-linked immunoassays
%K Antigens
%K Antibody response
%K Immune response
%K Respiratory syncytial virus
%K Vaccine development
%K Immunologic adjuvants
%U https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3000164