@article{6b0526c810e646759e82bd7d23a1bfef,
title = "Identification of Antibodies Targeting the H3N2 Hemagglutinin Receptor Binding Site following Vaccination of Humans",
abstract = "Antibodies targeting the receptor binding site (RBS) of the influenza virus hemagglutinin (HA) protein are usually not broadly reactive because their footprints are typically large and extend to nearby variable HA residues. Here, we identify several human H3N2 HA RBS-targeting monoclonal antibodies (mAbs) that are sensitive to substitutions in conventional antigenic sites and are therefore not broadly reactive. However, we also identify an H3N2 HA RBS-targeting mAb that is exceptionally broadly reactive despite being sensitive to substitutions in residues outside of the RBS. We show that similar antibodies are present at measurable levels in the sera of some individuals but that they are inefficiently elicited by conventional vaccines. Our data indicate that HA RBS-targeting antibodies can be effective against variable viral strains even when they are somewhat sensitive to substitutions in HA residues adjacent to the RBS.",
keywords = "antibodies, hemagglutinin, influenza, vaccine",
author = "Zost, {Seth J.} and Juhye Lee and Gumina, {Megan E.} and Kaela Parkhouse and Carole Henry and Wu, {Nicholas C.} and Lee, {Chang Chun D.} and Wilson, {Ian A.} and Wilson, {Patrick C.} and Bloom, {Jesse D.} and Hensley, {Scott E.}",
note = "Funding Information: This work was supported by the National Institute of Allergy and Infectious Diseases (1R01AI113047, S.E.H.; 1R01AI108686, S.E.H.; 1K99AI139445, N.C.W.; CEIRS HHSN272201400005C, P.C.W. J.D.B. and S.E.H.; 2T32AI007324, S.J.Z.). J.D.B. and S.E.H. hold Investigators in the Pathogenesis of Infectious Disease Awards from the Burroughs Wellcome Fund. C.-C.D.L. is sponsored by an Academia Sinica Fellowship, Academia Sinica, Taiwan. S.J.Z. J.L. M.E.G. K.P. N.C.W. and C.-C.D.L. completed experiments and analyzed data. C.H. and P.C.W. provided plasmids that express heavy and light chains of each mAb in this study. J.D.B. supervised mutational scanning experiments. I.A.W. supervised Fab experiments. S.E.H. conceived the project, supervised the project, and analyzed data. S.J.Z. and S.E.H. wrote the manuscript with input from all authors. S.E.H. reports receiving consulting fees from Sanofi Pasteur, Lumen, Novavax, and Merck. Funding Information: This work was supported by the National Institute of Allergy and Infectious Diseases ( 1R01AI113047 , S.E.H.; 1R01AI108686 , S.E.H.; 1K99AI139445 , N.C.W.; CEIRS HHSN272201400005C , P.C.W., J.D.B., and S.E.H.; 2T32AI007324 , S.J.Z.). J.D.B. and S.E.H. hold Investigators in the Pathogenesis of Infectious Disease Awards from the Burroughs Wellcome Fund . C.-C.D.L. is sponsored by an Academia Sinica Fellowship , Academia Sinica, Taiwan . Publisher Copyright: {\textcopyright} 2019 The Author(s)",
year = "2019",
month = dec,
day = "24",
doi = "10.1016/j.celrep.2019.11.084",
language = "English (US)",
volume = "29",
pages = "4460--4470.e8",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "13",
}