Different mechanisms of antibody-mediated neutralization of parvoviruses revealed using the Fab fragments of monoclonal antibodies.
Antibody binding and neutralization are major host defenses against viruses, yet the mechanisms are often not well understood. Eight monoclonal antibodies and their Fab fragments were tested for neutralization of canine parvovirus and feline panleukopenia virus. All IgGs neutralized >85% of virus infectivity. Two Fabs neutralized when present at 5 nM, while the others gave little or no neutralization even at 20-100 nM. The antibodies bind two antigenic sites on the capsids which overlap the binding site of the host transferrin receptor (TfR). There was no specific correlation between Fab binding affinity and neutralization. All Fabs reduced capsid binding of virus to purified feline TfR in vitro, but the highly neutralizing Fabs were more efficient competitors. All partially prevented binding and uptake of capsids by feline TfR on cells. The virus appears adapted to allow some infectivity in the presence of at least low levels of antibodies.
Nelson
Christian D S
CD
Baker Institute for Animal Health, Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA. cn38@cornell.edu
Palermo
Laura M
LM
Hafenstein
Susan L
SL
Parrish
Colin R
CR
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology*; D000915:Antibody Affinity; D000956:Antigens, Viral / Q000276:immunology; D001667:Binding, Competitive / Q000276:immunology; D002213:Capsid / Q000276:immunology; D002460:Cell Line; D000939:Epitopes; D007140:Immunoglobulin Fab Fragments / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology; D005256:Leukemia Virus, Feline / Q000276:immunology*; D009500:Neutralization Tests; D017993:Parvovirus, Canine / Q000276:immunology; D011485:Protein Binding / Q000276:immunology; D011990:Receptors, Transferrin / Q000276:immunology
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000956:Antigens, Viral; D000939:Epitopes; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D011990:Receptors, Transferrin