Vaccine design via antigen reorientation.
Nat Chem Biol
; 20(8): 1012-1021, 2024 Aug.
Article
en En
| MEDLINE
| ID: mdl-38225471
ABSTRACT
A major challenge in creating universal influenza vaccines is to focus immune responses away from the immunodominant, variable head region of hemagglutinin (HA-head) and toward the evolutionarily conserved stem region (HA-stem). Here we introduce an approach to control antigen orientation via site-specific insertion of aspartate residues that facilitates antigen binding to alum. We demonstrate the generalizability of this approach with antigens from Ebola, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza viruses and observe enhanced neutralizing antibody responses in all cases. We then reorient an H2 HA in an 'upside-down' configuration to increase the exposure and immunogenicity of HA-stem. The reoriented H2 HA (reoH2HA) on alum induced stem-directed antibodies that cross-react with both group 1 and group 2 influenza A subtypes. Electron microscopy polyclonal epitope mapping (EMPEM) revealed that reoH2HA (group 1) elicits cross-reactive antibodies targeting group 2 HA-stems. Our results highlight antigen reorientation as a generalizable approach for designing epitope-focused vaccines.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Vacunas contra la Influenza
/
SARS-CoV-2
Límite:
Animals
/
Humans
Idioma:
En
Año:
2024
Tipo del documento:
Article