Influenza Antigen Engineering Focuses Immune Responses to a Subdominant but Broadly Protective Viral Epitope.
Animals
Antibodies, Viral
/ immunology
Crystallography, X-Ray
Epitopes
/ chemistry
Glycosylation
Hemagglutinin Glycoproteins, Influenza Virus
/ chemistry
Immunization, Passive
Influenza A Virus, H3N2 Subtype
/ genetics
Mice, Inbred BALB C
Orthomyxoviridae Infections
/ prevention & control
Polysaccharides
/ metabolism
Protein Binding
Protein Conformation
Survival Analysis
broadly neutralizing antibodies
immunogen design
influenza hemagglutinin
protein engineering
Journal
Cell host & microbe
ISSN: 1934-6069
Titre abrégé: Cell Host Microbe
Pays: United States
ID NLM: 101302316
Informations de publication
Date de publication:
12 Jun 2019
12 Jun 2019
Historique:
received:
31
01
2019
revised:
12
03
2019
accepted:
08
04
2019
pubmed:
21
5
2019
medline:
24
12
2019
entrez:
21
5
2019
Statut:
ppublish
Résumé
Viral glycoproteins are under constant immune surveillance by a host's adaptive immune responses. Antigenic variation including glycan introduction or removal is among the mechanisms viruses have evolved to escape host immunity. Understanding how glycosylation affects immunodominance on complex protein antigens may help decipher underlying B cell biology. To determine how B cell responses can be altered by such modifications, we engineered glycans onto the influenza virus hemagglutinin (HA) and characterized the molecular features of the elicited humoral immunity in mice. We found that glycan addition changed the initially diverse antibody repertoire into an epitope-focused, genetically restricted response. Structural analyses showed that one antibody gene family targeted a previously subdominant, occluded epitope at the head interface. Passive transfer of this antibody conferred Fc-dependent protection to influenza virus-challenged mice. These results have potential implications for next-generation viral vaccines aimed at directing B cell responses to preferred epitope(s).
Identifiants
pubmed: 31104946
pii: S1931-3128(19)30206-9
doi: 10.1016/j.chom.2019.04.003
pmc: PMC6748655
mid: NIHMS1529796
pii:
doi:
Substances chimiques
Antibodies, Viral
0
Epitopes
0
Hemagglutinin Glycoproteins, Influenza Virus
0
Polysaccharides
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
827-835.e6Subventions
Organisme : NINR NIH HHS
ID : R01 NR003126
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI128832
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI089618
Pays : United States
Organisme : NIAID NIH HHS
ID : UC6 AI058607
Pays : United States
Organisme : NIGMS NIH HHS
ID : P41 GM103403
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA006516
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI117892
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.
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