Boosting subdominant neutralizing antibody responses with a computationally designed epitope-focused immunogen

Abstract : 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.
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Submitted on : Friday, May 24, 2019 - 11:10:57 AM
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Fabian Sesterhenn, Marie Galloux, Sabrina Vollers, Lucia Csepregi, Che Yang, et al.. Boosting subdominant neutralizing antibody responses with a computationally designed epitope-focused immunogen. PLoS Biology, Public Library of Science, 2019, 17 (2), pp.e3000164. ⟨10.1371/journal.pbio.3000164⟩. ⟨inserm-02138858⟩

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