Multivalent display of engineered HIV-1 envelope trimers on silica nanoparticles for targeting and in vitro activation of germline VRC01 B cells.

Silicon Dioxide HIV-1
Affinity Avidity B cells Env Germline-targeting HIV-1 Immunogen design Multivalent interaction Nanotechnology Silica nanoparticles Vaccine

Journal

European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V
ISSN: 1873-3441
Titre abrégé: Eur J Pharm Biopharm
Pays: Netherlands
ID NLM: 9109778

Informations de publication

Date de publication:
Dec 2022
Historique:
received: 18 08 2022
revised: 04 10 2022
accepted: 09 10 2022
pubmed: 23 10 2022
medline: 15 12 2022
entrez: 22 10 2022
Statut: ppublish

Résumé

Selective targeting of germline B cells with specifically designed germline-targeting HIV-1 envelope immunogens (GT-Env) is considered a feasible vaccination strategy to elicit broadly neutralizing antibodies (bnAbs). BnAbs are extremely valuable because they neutralize genetically distant viral strains at the same time. To overcome its inherently low affinity to germline B cells, the aim of the study was to present GT-Env via different immobilization strategies densely arrayed on the surface of nanoparticles. We engineered a prefusion-stabilized GT-Env trimer with affinity to VRC01 germline B cells using a bioinformatics-supported design approach. Distinct glycan modifications and amino acid substitutions yielded a GT-Env trimer which bound to the receptor with a K

Identifiants

DOI: 10.1016/j.ejpb.2022.10.007 PMID: 36272655
pubmed: 36272655
pii: S0939-6411(22)00234-X
doi: 10.1016/j.ejpb.2022.10.007
pii:
doi:

Substances chimiques

Silicon Dioxide 7631-86-9

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

88-101

Informations de copyright

Copyright © 2022 Elsevier B.V. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Auteurs

David Peterhoff (D)

Institute of Medical Microbiology and Hygiene, Molecular Microbiology (Virology), University of Regensburg, 93040 Regensburg, Germany; Institute of Clinical Microbiology and Hygiene, University Hospital Regensburg, 93053 Regensburg, Germany. Electronic address: david.peterhoff@ur.de.

Stefanie Thalhauser (S)

Department of Pharmaceutical Technology, University of Regensburg, 93040 Regensburg, Germany.

Patrick Neckermann (P)

Institute of Medical Microbiology and Hygiene, Molecular Microbiology (Virology), University of Regensburg, 93040 Regensburg, Germany.

Clara Barbey (C)

Department of Pharmaceutical Technology, University of Regensburg, 93040 Regensburg, Germany.

Kristina Straub (K)

Regensburg Center for Biochemistry, University of Regensburg, 93040 Regensburg, Germany.

Julian Nazet (J)

Regensburg Center for Biochemistry, University of Regensburg, 93040 Regensburg, Germany.

Rainer Merkl (R)

Regensburg Center for Biochemistry, University of Regensburg, 93040 Regensburg, Germany.

Gernot Laengst (G)

Regensburg Center for Biochemistry, University of Regensburg, 93040 Regensburg, Germany.

Miriam Breunig (M)

Department of Pharmaceutical Technology, University of Regensburg, 93040 Regensburg, Germany. Electronic address: miriam.breunig@ur.de.

Ralf Wagner (R)

Institute of Medical Microbiology and Hygiene, Molecular Microbiology (Virology), University of Regensburg, 93040 Regensburg, Germany; Institute of Clinical Microbiology and Hygiene, University Hospital Regensburg, 93053 Regensburg, Germany. Electronic address: ralf.wagner@ur.de.

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Classifications MeSH

questionsmedicales.fr › Produits chimiques inorganiques › Composés du silicium › Silice › Multivalent display of engineered HIV-1...
questionsmedicales.fr › Virus › Virus à ARN › Retroviridae › Lentivirus › Lentivirus des primates › VIH (Virus de l'Immunodéficience Humaine) › VIH-1 (Virus de l'Immunodéficience Humaine de type 1) › Multivalent display of engineered HIV-1...