The role of antibody concentration and avidity in antiviral protection.
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.
Bachmann
M F
MF
Institute of Experimental Immunology, Department of Pathology, University Hospital Zürich, Schmelzbergstrasse 12, CH-8091 Zürich, Switzerland.
Kalinke
U
U
Althage
A
A
Freer
G
G
Burkhart
C
C
Roost
H
H
Aguet
M
M
Hengartner
H
H
Zinkernagel
R M
RM
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
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; C028391:G protein, vesicular stomatitis virus; D006023:Glycoproteins; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins; D014759:Viral Envelope Proteins