Boosting subdominant neutralizing antibody responses with a computationally designed epitope-focused immunogen.
PLoS Biol
; 17(2): e3000164, 2019 02.
Article
in En
| MEDLINE
| ID: mdl-30789898
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Respiratory Syncytial Viruses
/
Recombinant Fusion Proteins
/
Receptors, Antigen, B-Cell
/
Viral Fusion Proteins
/
Antibodies, Neutralizing
/
Antibodies, Viral
/
Epitopes
Language:
En
Journal:
PLoS Biol
Journal subject:
BIOLOGIA
Year:
2019
Document type:
Article
Affiliation country:
Switzerland