Murine model for pertussis vaccine encephalopathy: role of the major histocompatibility complex; antibody to albumin and to Bordetella pertussis and pertussis toxin.
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)
Steinman
L
L
Weiss
A
A
Adelman
N
N
Lim
M
M
Oehlert
J
J
Zuniga
R
R
Hewlett
E
E
Falkow
S
S
D037361:Adenylate Cyclase Toxin; D000818:Animals; D000917:Antibody Formation; D001886:Bordetella pertussis / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity; D001927:Brain Diseases / Q000209:etiology* / Q000276:immunology; D003165:Complement System Proteins / Q000276:immunology; D003429:Cross Reactions; D004195:Disease Models, Animal; D006183:H-2 Antigens / Q000276:immunology; D007116:Immunization, Passive; D051379:Mice; D008815:Mice, Inbred Strains; D009154:Mutation; D037342:Pertussis Toxin; D010567:Pertussis Vaccine / Q000276:immunology; D012710:Serum Albumin, Bovine / Q000276:immunology; D010566:Virulence Factors, Bordetella / Q000276:immunology
D037361:Adenylate Cyclase Toxin; D006183:H-2 Antigens; D010567:Pertussis Vaccine; D010566:Virulence Factors, Bordetella; D012710:Serum Albumin, Bovine; D003165:Complement System Proteins; D037342:Pertussis Toxin