title: The role of antibody concentration and avidity in antiviral protection.
abstract: Neutralizing antibodies are necessary and sufficient for protection against infection with vesicular stomatitis virus (VSV). The in vitro neutralization capacities and in vivo protective capacities of a panel of immunoglobulin G monoclonal antibodies to the glycoprotein of VSV were evaluated. In vitro, neutralizing activity correlated with avidity and with neutralization rate constant, a measure of on-rate. However, in vivo, protection was independent of immunoglobulin subclass, avidity, neutralization rate constant, and in vitro neutralizing activity; above a minimal avidity threshold, protection depended simply on a minimum serum concentration. These two biologically defined thresholds of antibody specificity offer hope for the development of adoptive therapy with neutralizing antibodies.
authors.affiliation: Institute of Experimental Immunology, Department of Pathology, University Hospital Zürich, Schmelzbergstrasse 12, CH-8091 Zürich, Switzerland.
authors.forename: M F
authors.initials: MF
authors.lastname: Bachmann
authors.forename: U
authors.initials: U
authors.lastname: Kalinke
authors.forename: A
authors.initials: A
authors.lastname: Althage
authors.forename: G
authors.initials: G
authors.lastname: Freer
authors.forename: C
authors.initials: C
authors.lastname: Burkhart
authors.forename: H
authors.initials: H
authors.lastname: Roost
authors.forename: M
authors.initials: M
authors.lastname: Aguet
authors.forename: H
authors.initials: H
authors.lastname: Hengartner
authors.forename: R M
authors.initials: RM
authors.lastname: Zinkernagel
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000097:blood / Q000276:immunology; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology*; D000915:Antibody Affinity; D000918:Antibody Specificity; D001921:Brain / Q000821:virology; D004797:Enzyme-Linked Immunosorbent Assay; D006023:Glycoproteins / Q000276:immunology; D007116:Immunization, Passive; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D008562:Membrane Glycoproteins; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D009500:Neutralization Tests; D018353:Rhabdoviridae Infections / Q000276:immunology* / Q000821:virology; D014721:Vesicular stomatitis Indiana virus / Q000254:growth & development / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; C028391:G protein, vesicular stomatitis virus; D006023:Glycoproteins; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins; D014759:Viral Envelope Proteins