Assessing immunogenicity barriers of the HIV-1 envelope trimer.
Journal
NPJ vaccines
ISSN: 2059-0105
Titre abrégé: NPJ Vaccines
Pays: England
ID NLM: 101699863
Informations de publication
Date de publication:
30 Sep 2023
30 Sep 2023
Historique:
received:
12
04
2023
accepted:
19
09
2023
medline:
1
10
2023
pubmed:
1
10
2023
entrez:
30
9
2023
Statut:
epublish
Résumé
Understanding the balance between epitope shielding and accessibility on HIV-1 envelope (Env) trimers is essential to guide immunogen selection for broadly neutralizing antibody (bnAb) based vaccines. To investigate the antigenic space of Env immunogens, we created a strategy based on synthetic, high diversity, Designed Ankyrin Repeat Protein (DARPin) libraries. We show that DARPin Antigenicity Analysis (DANA), a purely in vitro screening tool, has the capability to extrapolate relevant information of antigenic properties of Env immunogens. DANA screens of stabilized, soluble Env trimers revealed that stronger trimer stabilization led to the selection of highly mutated DARPins with length variations and framework mutations mirroring observations made for bnAbs. By mimicking heterotypic prime-boost immunization regimens, DANA may be used to select immunogen combinations that favor the selection of trimer-reactive binders. This positions DANA as a versatile strategy for distilling fundamental antigenic features of immunogens, complementary to preclinical immunogenicity testing.
Identifiants
pubmed: 37777519
doi: 10.1038/s41541-023-00746-3
pii: 10.1038/s41541-023-00746-3
pmc: PMC10542815
doi:
Types de publication
Journal Article
Langues
eng
Pagination
148Subventions
Organisme : Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation)
ID : 314730_172790
Organisme : Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation)
ID : 33CS30_201369
Organisme : Swiss HIV Cohort Research Foundation
ID : 744
Organisme : EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)
ID : 681032
Organisme : EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)
ID : 681032
Informations de copyright
© 2023. Springer Nature Limited.
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