title: HA Antibody-Mediated FcγRIIIa Activity Is Both Dependent on FcR Engagement and Interactions between HA and Sialic Acids.
abstract: Interactions with receptors for the Fc region of IgG (FcγRs) have been shown to contribute to thein vivoprotection against influenza A viruses provided by broadly neutralizing antibodies (bnAbs) that bind to the viral hemagglutinin (HA) stem. In particular, Fc-mediated antibody-dependent cellular cytotoxicity (ADCC) has been shown to contribute to protection by stem-binding bnAbs. Fc-mediated effector functions appear not to contribute to protection provided by strain-specific HA head-binding antibodies. We used a panel of anti-stem and anti-head influenza A and B monoclonal antibodies with identical human IgG1 Fc domains and investigated their ability to mediate ADCC-associated FcγRIIIa activation. Antibodies which do not interfere with sialic acid binding of HA can mediate FcγRIIIa activation. However, the FcγRIIIa activation was inhibited when a mutant HA, unable to bind sialic acids, was used. Antibodies which block sialic acid receptor interactions of HA interfered with FcγRIIIa activation. The inhibition of FcγRIIIa activation by HA head-binding and sialic acid receptor-blocking antibodies was confirmed in plasma samples of H5N1 vaccinated human subjects. Together, these results suggest that in addition to Fc-FcγR binding, interactions between HA and sialic acids on immune cells are required for optimal Fc-mediated effector functions by anti-HA antibodies.
authors.affiliation: Janssen Prevention Center, Janssen Pharmaceutical Companies of Johnson & Johnson , Leiden , Netherlands.
authors.forename: Freek
authors.initials: F
authors.lastname: Cox
authors.affiliation: Janssen Prevention Center, Janssen Pharmaceutical Companies of Johnson & Johnson , Leiden , Netherlands.
authors.forename: Ted
authors.initials: T
authors.lastname: Kwaks
authors.affiliation: Janssen Prevention Center, Janssen Pharmaceutical Companies of Johnson & Johnson , Leiden , Netherlands.
authors.forename: Boerries
authors.initials: B
authors.lastname: Brandenburg
authors.affiliation: Janssen Prevention Center, Janssen Pharmaceutical Companies of Johnson & Johnson , Leiden , Netherlands.
authors.forename: Martin H
authors.initials: MH
authors.lastname: Koldijk
authors.affiliation: Janssen Prevention Center, Janssen Pharmaceutical Companies of Johnson & Johnson , Leiden , Netherlands.
authors.forename: Vincent
authors.initials: V
authors.lastname: Klaren
authors.affiliation: Janssen Prevention Center, Janssen Pharmaceutical Companies of Johnson & Johnson , Leiden , Netherlands.
authors.forename: Bastiaan
authors.initials: B
authors.lastname: Smal
authors.affiliation: Janssen Prevention Center, Janssen Pharmaceutical Companies of Johnson & Johnson , Leiden , Netherlands.
authors.forename: Hans J W M
authors.initials: HJ
authors.lastname: Korse
authors.affiliation: Janssen Prevention Center, Janssen Pharmaceutical Companies of Johnson & Johnson , Leiden , Netherlands.
authors.forename: Eric
authors.initials: E
authors.lastname: Geelen
authors.affiliation: Janssen Prevention Center, Janssen Pharmaceutical Companies of Johnson & Johnson , Leiden , Netherlands.
authors.forename: Lisanne
authors.initials: L
authors.lastname: Tettero
authors.affiliation: Janssen Prevention Center, Janssen Pharmaceutical Companies of Johnson & Johnson , Leiden , Netherlands.
authors.forename: David
authors.initials: D
authors.lastname: Zuijdgeest
authors.affiliation: Janssen Prevention Center, Janssen Pharmaceutical Companies of Johnson & Johnson , Leiden , Netherlands.
authors.forename: Esther J M
authors.initials: EJ
authors.lastname: Stoop
authors.affiliation: Janssen Prevention Center, Janssen Pharmaceutical Companies of Johnson & Johnson , Leiden , Netherlands.
authors.forename: Eirikur
authors.initials: E
authors.lastname: Saeland
authors.affiliation: Janssen Prevention Center, Janssen Pharmaceutical Companies of Johnson & Johnson , Leiden , Netherlands.
authors.forename: Ronald
authors.initials: R
authors.lastname: Vogels
authors.affiliation: Janssen Prevention Center, Janssen Pharmaceutical Companies of Johnson & Johnson , Leiden , Netherlands.
authors.forename: Robert H E
authors.initials: RH
authors.lastname: Friesen
authors.affiliation: Janssen Prevention Center, Janssen Pharmaceutical Companies of Johnson & Johnson , Leiden , Netherlands.
authors.forename: Wouter
authors.initials: W
authors.lastname: Koudstaal
authors.affiliation: Janssen Prevention Center, Janssen Pharmaceutical Companies of Johnson & Johnson , Leiden , Netherlands.
authors.forename: Jaap
authors.initials: J
authors.lastname: Goudsmit
keywords: ADCC; CR6261; CR8033; CR9114; Fc-receptor; head-binding antibody; hemagglutinin; stem-binding antibody