Heterosubtypic antibody recognition of the influenza virus hemagglutinin receptor binding site enhanced by avidity
Identifieur interne : 000A52 ( Main/Merge ); précédent : 000A51; suivant : 000A53Heterosubtypic antibody recognition of the influenza virus hemagglutinin receptor binding site enhanced by avidity
Auteurs : Peter S. Lee ; Reiko Yoshida [Japon] ; Damian C. Ekiert ; Naoki Sakai [Allemagne] ; Yasuhiko Suzuki [Japon] ; Ayato Takada [Japon] ; Ian A. WilsonSource :
- Proceedings of the National Academy of Sciences of the United States of America [ 0027-8424 ] ; 2012.
Abstract
Continual and rapid mutation of seasonal influenza viruses by antigenic drift necessitates the almost annual reformulation of flu vaccines, which may offer little protection if the match to the dominant circulating strain is poor. S139/1 is a cross-reactive antibody that neutralizes multiple HA strains and subtypes, including those from H1N1 and H3N2 viruses that currently infect humans. The crystal structure of the S139/1 Fab in complex with the HA from the A/Victoria/3/1975 (H3N2) virus reveals that the antibody targets highly conserved residues in the receptor binding site and contacts antigenic sites A, B, and D. Binding and plaque reduction assays show that the monovalent Fab alone can protect against H3 strains, but the enhanced avidity from binding of bivalent IgG increases the breadth of neutralization to additional strains from the H1, H2, H13, and H16 subtypes. Thus, antibodies making relatively low affinity Fab interactions with the receptor binding site can have significant antiviral activity when enhanced by avidity through bivalent interactions of the IgG, thereby extending the breadth of binding and neutralization to highly divergent influenza virus strains and subtypes.
Url:
DOI: 10.1073/pnas.1212371109
PubMed: 23027945
PubMed Central: 3479480
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PMC:3479480Le document en format XML
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<author><name sortKey="Lee, Peter S" sort="Lee, Peter S" uniqKey="Lee P" first="Peter S." last="Lee">Peter S. Lee</name>
<affiliation><nlm:aff id="aff1">Department of Molecular Biology and The Skaggs Institute of Chemical Biology,<institution>The Scripps Research Institute</institution>
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<author><name sortKey="Yoshida, Reiko" sort="Yoshida, Reiko" uniqKey="Yoshida R" first="Reiko" last="Yoshida">Reiko Yoshida</name>
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, Sapporo 001-0020,<country>Japan</country>
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<front><div type="abstract" xml:lang="en"><p>Continual and rapid mutation of seasonal influenza viruses by antigenic drift necessitates the almost annual reformulation of flu vaccines, which may offer little protection if the match to the dominant circulating strain is poor. S139/1 is a cross-reactive antibody that neutralizes multiple HA strains and subtypes, including those from H1N1 and H3N2 viruses that currently infect humans. The crystal structure of the S139/1 Fab in complex with the HA from the A/Victoria/3/1975 (H3N2) virus reveals that the antibody targets highly conserved residues in the receptor binding site and contacts antigenic sites A, B, and D. Binding and plaque reduction assays show that the monovalent Fab alone can protect against H3 strains, but the enhanced avidity from binding of bivalent IgG increases the breadth of neutralization to additional strains from the H1, H2, H13, and H16 subtypes. Thus, antibodies making relatively low affinity Fab interactions with the receptor binding site can have significant antiviral activity when enhanced by avidity through bivalent interactions of the IgG, thereby extending the breadth of binding and neutralization to highly divergent influenza virus strains and subtypes.</p>
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