title: Early high-affinity neutralizing anti-viral IgG responses without further overall improvements of affinity.
abstract: Affinity maturation of IgG antibodies in adaptive immune responses is a well-accepted mechanism to improve effector functions of IgG within 2 weeks to several months of antigen encounter. This concept has been defined mainly for IgG responses against chemically defined haptens. We have evaluated this concept in a viral system and analyzed neutralizing IgG antibody responses against vesicular stomatitis virus (a close relative of rabies virus) with a panel of monoclonal antibodies obtained early (day 6 or 12) and late (day 150) after hyperimmunization. These neutralizing IgG antibodies recognize a single major antigenic site with high affinities (Ka of 10(8)-10(10) liter.mol-1) and with rapid on-rates already on day 6 of a primary response and with no evidence for further antigen dose- and time-dependent overall improvement of affinity. This type of IgG response is probably representative for viruses or bacterial toxins which are crucially controlled by neutralizing antibodies.
authors.affiliation: Department of Pathology, University of Zürich, Switzerland.
authors.forename: H P
authors.initials: HP
authors.lastname: Roost
authors.forename: M F
authors.initials: MF
authors.lastname: Bachmann
authors.forename: A
authors.initials: A
authors.lastname: Haag
authors.forename: U
authors.initials: U
authors.lastname: Kalinke
authors.forename: V
authors.initials: V
authors.lastname: Pliska
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 / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology*; D000915:Antibody Affinity; D000956:Antigens, Viral / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D018604:Epitope Mapping; D005803:Genes, Immunoglobulin; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology*; D007700:Kinetics; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D051381:Rats; D013997:Time Factors; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology*; D014764:Viral Proteins / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000956:Antigens, Viral; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins; D014764:Viral Proteins