Modulation of Bordetella pertussis infection with monoclonal antibodies to pertussis toxin.
Three monoclonal antibodies to pertussis toxin were characterized and used to investigate its role in immunity. Antibody affinity correlated with toxin neutralization in in vivo and in vitro assays but was not the only determinant of protection against Bordetella pertussis infection. B9, a high-affinity anti-S3 antibody, was the most effective in neutralizing toxin-induced CHO cell clustering and hemagglutination in vitro and lymphocytosis and histamine sensitization in vivo. A4, a similar-affinity anti-S1 antibody, was less active in the toxin neutralization assays but more protective in the mouse infection model. A12, a low-affinity anti-S1 antibody, was least active in the assays of toxin neutralization but as effective as B9 in the infection model. These data suggest that epitopes on the A protomer and B oligomer may induce protective immunity. Measurement of pertussis toxin neutralization by monoclonal antibodies in in vitro and in vivo assays may not accurately predict protection against infection with B. pertussis.
Department of Pediatrics, Dalhousie University, Halifax, Canada.
S A
SA
Halperin
T B
TB
Issekutz
A
A
Kasina
D000818:Animals; D000907:Antibodies, Bacterial / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000918:Antibody Specificity; D001681:Biological Assay; D001886:Bordetella pertussis / Q000276:immunology; D004195:Disease Models, Animal; D000939:Epitopes / Q000276:immunology; D005260:Female; D006825:Hybridomas; D007116:Immunization, Passive; D007124:Immunoenzyme Techniques; D007958:Leukocyte Count; D051379:Mice; D008807:Mice, Inbred BALB C; D037342:Pertussis Toxin; D010566:Virulence Factors, Bordetella / Q000276:immunology*; D014917:Whooping Cough / Q000517:prevention & control*
D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D000939:Epitopes; D010566:Virulence Factors, Bordetella; D037342:Pertussis Toxin