Murine model for pertussis vaccine encephalopathy: role of the major histocompatibility complex; antibody to albumin and to Bordetella pertussis and pertussis toxin

Dev Biol Stand. 1985:61:439-46.


A mouse model for pertussis immunization encephalopathy has been described with features that closely resemble the severe adverse reactions occasionally seen after pertussis vaccine administration,m including seizures and a shock-like state leading to death. These reactions are produced with nearly one hundred percent efficiency provided that the mice immunized with Bordetella pertussis have 1) the appropriate major histocompatibility (H-2) genotype, 2) have been sensitized to bovine serum albumin (BSA), and 3) that the injected B. pertussis contained sufficient amounts of pertussis toxin. Antibody titres were measured in mice with haplotypes H-2d.s.k. that are highly susceptible to encephalopathy as well as in H-2b mice, that are totally resistant. Mice with H-2d.s.k. haplotypes were high responders to BSA, while H-2b (B10) mice were non-responders to BSA. Both H-2d and H-2b mice responded well to B. pertussis. Encephalopathy was induced in resistant H-2b mice with B. pertussis and passively administered anti-BSA antiserum, but not with B. pertussis and anti-(T,G)-A--L antibody. This indicated that B. pertussis and anti-BSA were absolutely required for development of encephalopathy. Encephalopathy could be induced in mice decomplemented with cobra venom factor and given BSA and B. pertussis. Several single-site mutants of B. pertussis affecting single virulence factors were induced with transposon Tn5. One of these mutants, BP357, deficient in pertussis toxin production, had a greatly reduced encephalopathic potential in the mouse model compared to the virulent strain BP 338, or to BP348, an adenylate cyclase and hemolysin double mutant, or to BP 349, a hemolysin mutant.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenylate Cyclase Toxin
  • Animals
  • Antibody Formation
  • Bordetella pertussis / genetics
  • Bordetella pertussis / immunology
  • Bordetella pertussis / pathogenicity
  • Brain Diseases / etiology*
  • Brain Diseases / immunology
  • Complement System Proteins / immunology
  • Cross Reactions
  • Disease Models, Animal
  • H-2 Antigens / immunology
  • Immunization, Passive
  • Mice
  • Mice, Inbred Strains
  • Mutation
  • Pertussis Toxin
  • Pertussis Vaccine / immunology
  • Serum Albumin, Bovine / immunology
  • Virulence Factors, Bordetella / immunology


  • Adenylate Cyclase Toxin
  • H-2 Antigens
  • Pertussis Vaccine
  • Virulence Factors, Bordetella
  • Serum Albumin, Bovine
  • Complement System Proteins
  • Pertussis Toxin