Murine model for pertussis vaccine encephalopathy: linkage to H–2

Steinman, Lawrence; Subramaniam, Sriram; Adelman, Nancy; Zamvil, Scott S.; McDevitt, Hugh O.; Urich, H.

doi:10.1038/299738a0

Cited by 33 publications

(26 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Steinman et al (1982) also reported that resistance to Bordetella pertussis vaccine encephalopathy was associated with the mouse MHC. Our results show that the many elegant studies on mice and man, linking the MHC with disease resistance, can be applied to domestic species such as the pig.…”

Section: Discussionmentioning

confidence: 99%

Breed and Swine Lymphocyte Antigen Haplotype Differences in Agglutination Titers Following Vaccination with B. Bronchiseptica2

Rothschild

Chen

Christian

et al. 1984

Journal of Animal Science

View full text Add to dashboard Cite

Genetic differences in immune response to B. bronchiseptica after vaccination with a commercial B. bronchiseptica bacterin were investigated in 1,069 8-wk-old pigs. These pigs were from 65 litters born in the spring and 66 litters born in the fall of 1982 and were purebreds from the Chester White (n = 128), Duroc (n = 281), Hampshire (n = 143), Landrace (n = 309) and Yorkshire (n = 208) breeds. Each litter was raised separately. Individual pigs were vaccinated im at 4 and 6 wk of age with 2 ml of B. bronchiseptica bacterin. At 8 wk of age, 8 ml of blood were collected from each animal and serum prepared to determine agglutinating antibody titers against B. bronchiseptica bacterin by a bacterial agglutination method. In addition, lymphocytes were separated from 1 ml of heparinized blood and used to determine Swine Lymphocyte Antigen (SLA) haplotypes by using cytotoxic antibodies against the SLA complex. Antisera for 3 SLA haplotypes were made available by the National Institutes of Health. Results indicated that breed of pig (P<.01) and dam of pig (P<.01) affected the immune response of the pig after B. bronchiseptica vaccination. Higher immune response was also associated (P<.05) with one of the SLA haplotypes tested. Heritability estimates for immune response following vaccination were .10 ± .12 (half-sib) and .42 ± .19 (full-sib). Results suggest that the relationship of the SLA complex to immune response in the pig and nonadditive genetic and maternal effects on immune response should be further investigated. SummaryGenetic differences in immune response to B. bronchiseptica after vaccination with a commercial B. bronchiseptica bacterin were investigated in 1,069 8-wk-old pigs. These pigs were from 65 litters born in the spring and 66 litters born in the fall of 1982 and were purebreds from the Chester White (n = 128), Duroc (n = 281), Hampshire (n = 143), Landrace (n = 309) and Yorkshire (n = 208) breeds. Each litter was raised separately. Individual pigs were vaccinated im at 4 and 6 wk of age with 2 ml of B. bronchiseptica bacterin. At 8 wk of age, 8 ml of blood were collected from each animal and serum prepared to determine agglutinating antibody titers against B. bronchiseptica bacterin by a bacterial agglutination method. In addition, lymphocytes were separated from 1 ml of heparinized blood and used to determine Swine Lymphocyte Antigen (SLA) haplotypes by using cytotoxic antibodies against the SLA complex. Antisera for 3 SLA haplotypes were made available by the National Institutes of Health. Results indicated that breed of pig (P<.01) and dam of pig (P<.O1) affected the immune response of the pig after B. bronchb septica vaccination. Higher immune response was also associated (P<.05) with one of the SLA haplotypes tested. Heritability estimates

show abstract

Section: Discussionmentioning

confidence: 99%

Breed and Swine Lymphocyte Antigen Haplotype Differences in Agglutination Titers Following Vaccination with B. Bronchiseptica2

Rothschild

Chen

Christian

et al. 1984

Journal of Animal Science

View full text Add to dashboard Cite

show abstract

“…Previous animal models designed to study the neurological responses to pertussis vaccine focused on an encephalopathic syndrome in mice generated by the administration of BSA and Pw (33). However, data from a number of groups indicate that the protocol induced an acute anaphylactic reaction and did not cause an encephalopathy (22,28).…”

Section: Discussionmentioning

confidence: 99%

“…Although it had been reported that repeated injection of Pw and bovine serum albumin (BSA) induced encephalopathy in mice (33), it was later demonstrated that the neurological responses observed resulted from the potentiating effect of pertussis toxin (PT) or LPS on anaphylaxis during sensitization to BSA (22,28). In this study we describe a novel murine model where neurological changes are consistently induced following parenteral administration of Pw.…”

mentioning

confidence: 99%

Whole-Cell but Not Acellular Pertussis Vaccines Induce Convulsive Activity in Mice: Evidence of a Role for Toxin-Induced Interleukin-1β in a New Murine Model for Analysis of Neuronal Side Effects of Vaccination

et al. 2001

View full text Add to dashboard Cite

Immunization with the whole-cell pertussis vaccine (Pw), while effective at preventing whooping cough in infants, has been associated with local, systemic, and neuronal reactions, including fevers and convulsions in children. In contrast, the new acellular pertussis vaccines (Pa) have a considerably improved safety profile. The lack of an appropriate animal model has restricted investigations into the mechanisms by which neurological reactions are induced by vaccination. Here we describe a novel murine model wherein seizure-like behavioral changes are induced following parenteral administration of Pw. The proinflammatory cytokine interleukin-␤ (IL-1␤), production of which has been associated with many neurodegenerative conditions, was significantly increased in the hippocampus and hypothalamus of vaccinated animals. Accompanying this change was a decrease in release of the inhibitory neurotransmitters ␥-aminobutyric acid and adenosine in the hippocampus. Seizure-like behavioral changes were significantly reduced following inhibition of IL-1␤ production by the administration of an inhibitor of IL-1␤-converting enzyme and were almost completely abrogated in IL-1 receptor type I knockout mice. These results suggest a causal relationship between IL-1␤ induction and convulsive behavior following Pw vaccination. Significantly, Pa neither increased IL-1␤ nor induced behavioral changes in mice, but did induce the anti-inflammatory cytokine IL-10. In contrast, administration of active pertussis toxin and lipopolysaccharide, residual in Pw but absent from Pa, also induced convulsive activity. Our findings provide the first direct evidence of an immunological basis for pertussis vaccine reactogenicity and suggest that active bacterial toxins are responsible for the neurologic disturbances observed in children immunized with Pw.

show abstract

“…were low responders to BSA and totally resistant to B. pertussis encephalopathy induced with whole cell pertussis vaccine (0/44 died) (4,5) TnS Insertion Mutants. TnS insertion mutants were derived from virulent strain BP338 (7).…”

mentioning

confidence: 99%

“…A lethal-shock-like syndrome preceded by mnyoclonic seizures is induced in mice with an appropriate major histocompatibility (H-2) gene after immunization with heat-killed Bordetella pertussis vaccine and bovine serum albumin (BSA) (4,5). This model, which resembles post-pertussis immunization encephalopathy, involves daily injections alternating BSA with vaccine for 4 days, then a BSA challenge 5 days later.…”

mentioning

confidence: 99%

Pertussis toxin is required for pertussis vaccine encephalopathy.

Steinman¹,

Weiss²,

Adelman³

et al. 1985

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

A mouse model for encephalopathy induced by pertussis immunization has been described; it has features that closely resemble some of the severe reactions, including seizures and a shock-like state leading to death, occasionally seen after administration of Bordetella pertusssis (whooping cough) vaccine. Susceptibility to encephalopathy maps to genes of the major histocompatibility complex and correlates as well with the genetic regulation of the level of antibody response to bovine serum albumin. In this study we have investigated which bacterial determinant is responsible for the encephalopathy. Two lines of evidence implicate pertussis toxin as the active bacterial component. Single-site mutants of B. pertussis with single affected virulence factors were tested. A mutant that produces a defective pertussis toxin had greatly diminished capacity to induce encephalopathy, whereas a hemolysin-and adenylate-cyclase-deficient avirulent mutant had the same activity in the mouse model as a virulent strain. Purified pertussis toxin plus bovine serum albumin was tested and found to induce the lethal encephalopathy, demonstrating that the toxin was the critical constituent of B. pertussis responsible for encephalopathy.The pertussis vaccine component of diphtheria-pertussis-tetanus (DPT) vaccine is associated with convulsions in one of 1750 doses (1), while severe and permanent neurologic damage has been calculated to occur with one of every 310,000 doses (2). Although the benefits of the current pertussis vaccination program outweight the-risks by a considerable margin (3), development of a safer, efficacious vaccine is an important goal. In the past this effort has been hampered by lack of definitive information "about which bacterial antigens were essential for vaccine efficacy and which bacterial products were responsible for the reactogenicity.A lethal-shock-like syndrome preceded by mnyoclonic seizures is induced in mice with an appropriate major histocompatibility (H-2) gene after immunization with heat-killed Bordetella pertussis vaccine and bovine serum albumin (BSA) (4, 5). This model, which resembles post-pertussis immunization encephalopathy, involves daily injections alternating BSA with vaccine for 4 days, then a BSA challenge 5 days later. Death usually results within minutes of the final challenge. Previous studies have shown that the linkage of susceptibility to pertussis vaccine encephalopathy i i associated with high antibody responsiveness to BSA. The strain distribution of high immune responsiveness to BSA was identical to that reported by Riley et al. (6) and conforms to our results with susceptibility to B. pertussis encephalopathy. Thus, H-2d mice were high responders to BSA and highly susceptible to encephalopathy (57/65 died), while H-2b mice The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby mnarked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this' fact.were low responders to BSA and totall...

show abstract

Murine model for pertussis vaccine encephalopathy: linkage to H–2

Cited by 33 publications

References 26 publications

Breed and Swine Lymphocyte Antigen Haplotype Differences in Agglutination Titers Following Vaccination with B. Bronchiseptica2

Breed and Swine Lymphocyte Antigen Haplotype Differences in Agglutination Titers Following Vaccination with B. Bronchiseptica2

Whole-Cell but Not Acellular Pertussis Vaccines Induce Convulsive Activity in Mice: Evidence of a Role for Toxin-Induced Interleukin-1β in a New Murine Model for Analysis of Neuronal Side Effects of Vaccination

Pertussis toxin is required for pertussis vaccine encephalopathy.

Contact Info

Product

Resources

About