Antibodies to a Conserved Influenza Head Interface Epitope Protect by an IgG Subtype-Dependent Mechanism

Watanabe, Akiko; McCarthy, Kevin R.; Kuraoka, Masayuki; Schmidt, Aaron G.; Adachi, Yu; Onodera, Taishi; Tonouchi, Keisuke; Caradonna, Timothy M.; Bajic, Goran; Song, Shengli; McGee, Charles E.; Sempowski, Gregory D.; Feng, Feng; Urick, Patricia; Kepler, Thomas B.; Takahashi, Yoshimasa; Harrison, Stephen C.; Kelsoe, Garnett

doi:10.1016/j.cell.2019.03.048

Antibodies to a Conserved Influenza Head Interface Epitope Protect by an IgG Subtype-Dependent Mechanism

Journal Article · Thu May 16 00:00:00 EDT 2019 · Cell

DOI:https://doi.org/10.1016/j.cell.2019.03.048· OSTI ID:1524669

Watanabe, Akiko ^[1]; McCarthy, Kevin R. ^[2]; Kuraoka, Masayuki ^[1]; Schmidt, Aaron G. ^[3]; Adachi, Yu ^[4]; Onodera, Taishi ^[4]; Tonouchi, Keisuke ^[4]; Caradonna, Timothy M. ^[3]; Bajic, Goran ^[2]; Song, Shengli ^[1]; McGee, Charles E. ^[5]; Sempowski, Gregory D. ^[5]; Feng, Feng ^[6]; Urick, Patricia ^[6]; Kepler, Thomas B. ^[6]; Takahashi, Yoshimasa ^[4]; Harrison, Stephen C. ^[7]; ^[5]

Duke Univ., Durham, NC (United States)
Boston Children’s Hospital, Harvard Medical School, Boston, MA (United States). Lab. of Molecular Medicine
Ragon Inst. and Harvard Medical School, Cambridge, MA (United States)
National Inst. of Infectious Diseases, Tokyo (Japan)
Duke Univ., Durham, NC (United States). Duke Human Vaccine Inst.
Boston Univ., MA (United States). School of Medicine
Boston Children’s Hospital, Harvard Medical School, Boston, MA (United States). Lab. of Molecular Medicine; Howard Hughes Medical Inst., Boston, MA (United States)

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. Lastly, antigens that present this broadly immunogenic HA epitope may be good candidates for inclusion in “universal” flu vaccines.

View Accepted Manuscript (DOE)

Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: National Institutes of Health (NIH). National Institute of General Medical Sciences (NIGMS); USDOE Office of Science (SC)

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 1524669

Journal Information:: Cell, Journal Name: Cell Journal Issue: 5 Vol. 177; ISSN 0092-8674

Publisher:: ElsevierCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

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