Pertussis toxin enhanced IgG1 and IgE responses to primary tetanus immunization are mediated by interleukin-4 and persist during secondary responses to tetanus alone.
Pertussis toxin (Ptx), the major toxin product of Bordetella pertussis, has potent immunologic effect including adjuvant effects on antibody responses and sensitization for anaphylaxis. In order to further define the effect of Ptx on the class and subclass of murine antibody response, we measured total and antigen specific IgG subclasses and IgE in Balb/c mice after primary and secondary immunization with tetanus toxoid (TT). Low doses of Ptx (100 ng) given intravenously at the time of primary immunization increased primary IgG1 and IgE anti-TT antibodies as well as total IgG1 and IgE concentrations compared to controls. The increase in IgG1 subclass and IgE response when Ptx was present during primary immunization was even more pronounced after secondary immunization with TT alone 3 weeks or 3 months later. Similar effects were noted after diphtheria toxoid immunization in the presence of Ptx. Administration of the anti IL-4 monoclonal antibody (11B11) suppressed the enhanced total and TT-specific IgE responses but not the enhanced IgG1 responses. The presence of low concentrations of Ptx during primary immunization primes for induction of IL-4 producing T-cell help which enhances IgGI and IgE responses to the primary exposure as well as to subsequent exposures of the antigen in the absence of Ptx. This phenomenon may have significance for the adjuvant activity of vaccines containing Ptx as well as for the immune response to natural pertussis.
Samore
M H
MH
Laboratory of Infectious Diseases, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Siber
G R
GR
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis*; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D004168:Diphtheria Toxoid / Q000494:pharmacology; D004357:Drug Synergism; D000939:Epitopes; D005260:Female; D007114:Immunization; D007117:Immunization, Secondary; D007073:Immunoglobulin E / Q000096:biosynthesis*; D007074:Immunoglobulin G / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000276:immunology / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D037342:Pertussis Toxin; D013745:Tetanus Toxoid / Q000276:immunology / Q000494:pharmacology*; D010566:Virulence Factors, Bordetella / Q000276:immunology / Q000494:pharmacology*
D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D004168:Diphtheria Toxoid; D000939:Epitopes; D007074:Immunoglobulin G; D013745:Tetanus Toxoid; D010566:Virulence Factors, Bordetella; D015847:Interleukin-4; D007073:Immunoglobulin E; D037342:Pertussis Toxin