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© Research
Publication : PLoS biology

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

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in PLoS biology - 01 Feb 2019

Sesterhenn F, Galloux M, Vollers SS, Csepregi L, Yang C, Descamps D, Bonet J, Friedensohn S, Gainza P, Corthésy P, Chen M, Rosset S, Rameix-Welti MA, Éléouët JF, Reddy ST, Graham BS, Riffault S, Correia BE,

Link to Pubmed [PMID] – 30789898

Link to DOI – e300016410.1371/journal.pbio.3000164

PLoS Biol 2019 Feb; 17(2): e3000164

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.

https://pubmed.ncbi.nlm.nih.gov/30789898