Antibodies to a Conserved Influenza Head Interface Epitope Protect by an IgG Subtype-Dependent Mechanism.
Journal Article (Journal Article)
Vaccines to generate durable humoral immunity against antigenically evolving pathogens such as the influenza virus must elicit antibodies that recognize conserved epitopes. Analysis of single memory B cells from immunized human donors has led us to characterize a previously unrecognized epitope of influenza hemagglutinin (HA) that is immunogenic in humans and conserved among influenza subtypes. Structures show that an unrelated antibody from a participant in an experimental infection protocol recognized the epitope as well. IgGs specific for this antigenic determinant do not block viral infection in vitro, but passive administration to mice affords robust IgG subtype-dependent protection against influenza infection. The epitope, occluded in the pre-fusion form of HA, is at the contact surface between HA head domains; reversible molecular "breathing" of the HA trimer can expose the interface to antibody and B cells. Antigens that present this broadly immunogenic HA epitope may be good candidates for inclusion in "universal" flu vaccines.
Full Text
Duke Authors
Cited Authors
- Watanabe, A; McCarthy, KR; Kuraoka, M; Schmidt, AG; Adachi, Y; Onodera, T; Tonouchi, K; Caradonna, TM; Bajic, G; Song, S; McGee, CE; Sempowski, GD; Feng, F; Urick, P; Kepler, TB; Takahashi, Y; Harrison, SC; Kelsoe, G
Published Date
- May 16, 2019
Published In
Volume / Issue
- 177 / 5
Start / End Page
- 1124 - 1135.e16
PubMed ID
- 31100267
Pubmed Central ID
- PMC6825805
Electronic International Standard Serial Number (EISSN)
- 1097-4172
Digital Object Identifier (DOI)
- 10.1016/j.cell.2019.03.048
Language
- eng
Conference Location
- United States