Boosting subdominant neutralizing antibody responses with a computationally designed epitope-focused immunogen - INRAE - Institut national de recherche pour l’agriculture, l’alimentation et l’environnement
Journal Articles PLoS Biology Year : 2019

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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hal-04671074 , version 1 (13-08-2024)

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Fabian Sesterhenn, Marie Galloux, Sabrina S Vollers, Lucia Csepregi, Che Yang, et al.. Boosting subdominant neutralizing antibody responses with a computationally designed epitope-focused immunogen. PLoS Biology, 2019, 17 (2), pp.e3000164. ⟨10.1371/journal.pbio.3000164⟩. ⟨hal-04671074⟩
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