Vaccines used to induce disease in animals
See: SICK MONKEYS: RESEARCH LINKS VACCINE LOAD, AUTISM SIGNS
RABIES VACCINE--INDUCING EXPERIMENTAL ENCEPHALITIS (EAE) IN ANIMALS
RS, et al.
Semple rabies vaccine: presence of myelin basic protein and proteolipid protein and its activity in experimental allergic encephalomyelitis. J Neurol Sci. 1989 Nov;93(2-3):221-30. PMID: 2480399; UI: 90079513.
Myelin basic protein (MBP) as a cause of postvaccinal encephalomyelitis (PVE) due to Semple rabies vaccine (SRV) has been suggested in previous reports. No actual measurement of MBP in SRV was done. In this study we detected MBP and PLP in the vaccine using immunological methods. The vaccine was found to contain 28 micrograms MBP per ml vaccine. Inoculation with SRV plus adjuvant resulted in the development of experimental allergic encephalomyelitis (EAE) in 2 of 3 guinea pigs. For control, chick embryo vaccine (CEV) was used and MBP was not detected. EAE was not induced in animals inoculated with it. These results suggest that MBP in vaccines may play a decisive role in the production of PVE.
S, et al.
Association of HLA and T-cell receptor gene polymorphisms with Semple rabies vaccine-induced autoimmune encephalomyelitis. Ann Neurol. 1999 May;45(5):595-600. PMID: 10319881; UI: 99251599. Semple rabies vaccine is derived from brain tissue infected with rabies virus that is subsequently inactivated with phenol. Semple rabies vaccine-induced autoimmune encephalomyelitis (SAE) occurs in 1 in 220 immunized individuals. The immune response to myelin basic protein and pathological changes of demyelination in SAE suggest that this disease is the human homologue of experimental autoimmune encephalomyelitis (EAE). SAE and EAE are frequently studied as models for the human demyelinating disease multiple sclerosis
Griffin DE. Monophasic autoimmune inflammatory diseases of the CNS and PNS. Res Publ Assoc Res Nerv Ment Dis. 1990;68:91-104. Review. PMID: 1970192; UI: 90222719.
Post-rabies vaccine encephalomyelitis, postinfectious encephalomyelitis, and acute inflammatory demyelinating polyneuropathy are all monophasic, inflammatory, demyelinating diseases that appear to be autoimmune in pathogenesis and induced by prior antigenic stimulation or infection. The primary encephalitogen for rabies vaccine and postinfectious encephalomyelitis appears to be MBP, with a possible augmenting role for the myelin glycolipids. The primary neuritogen in AIDP may be a glycolipid, but this has not been clearly established. The mechanism by which a prior, apparently unrelated, stimulus leads to postinfectious encephalomyelitis or AIDP is unclear, but abnormalities of immune regulation, possible molecular mimicry between infectious agents and neural constituents, and genetic susceptibility may each play important roles (Table 1).
AND PERTUSSIS VACCINE USED TO INDUCE ENCEPHALOPATHY IN ANIMALS
Animal models to control the serious neurological complications after vaccination against whooping cough are not available. In a recent paper pertussis vaccine induced acute encephalopathy in certain mouse strains (1). Healthy BALB/c mice died with shock-like symptoms after immunization with bovine serum albumin (BSA) and heat-killed pertussis. Mice not sensitized with BSA survived, and mice of strains with another H-2 type than H-2d were not susceptible. The authors concluded that the susceptibility to side effects to pertussis vaccine in mice and possibly in human is linked to the MHC. We tried to repeat the experiments reported by Steinman et al. in the hope that the murine encephalopathy model would be useful to evaluate possible neurological complications. In spite of having the same H-2d genotype, the BALB/c mice of two breeding stocks did not develop shock-like symptoms with fatal consequences after the last injection with BSA. This fact corresponds possibly with the author's observation that the pertussis vaccine encephalopathy is not under the control of H-2 genes alone. As shown in our tests the sudden deaths and encephalopathy in mice are not linked to BSA-sensitization because mice who received pertussis vaccine only showed the same symptoms as mice injected with BSA and vaccine. Histology did not indicate brain damage. It seems obvious that the deaths in our experiments were caused by the pertussis toxins present in the large numbers of bacteria given.
Munoz JJ; Peacock MG; Hadlow WJ Anaphylaxis or so-called encephalopathy in
mice sensitized to an antigen with the aid of pertussigen (pertussis toxin). Infect Immun,
55: 4, 1987 Apr, 1004-8
Sensitization of mice with 1 mg of bovine serum albumin (BSA) or chicken egg albumin (EA) given intraperitoneally and 300 to 400 ng of pertussigen (pertussis toxin [Ptx]) given intravenously (i.v.) induced a high degree of anaphylactic sensitivity when the mice were challenged i.v. with 1 mg of antigen 14 days later. Regardless of H-2 haplotype, all of the strains tested (CFW, BALB/cJ, DBA/2J, and C3H.SW/SnJ) were susceptible to anaphylaxis. Sensitization of mice by a multiple-dose procedure that has been reported to induce fatal encephalopathy in mice (L. Steinman, A. Weiss, N. Adelman, M. Lim, R. Zuniga, J. Oehlert, E. Hewlett, and S. Falkow, Proc. Natl. Acad. Sci. USA 82, 8733-8736, 1982) (1 mg of BSA on day -1, 100 to 400 ng of Ptx on day zero 1 mg of BSA on day +1, 100 to 400 ng of Ptx on day +2, and 1 mg of BSA on day +6) induced shock in BALB/cJ, DBA/2J, and C3H.SW/SnJ mice, but not in CFW mice. When EA was used instead of BSA, CFW, BALB/cJ, and C3H.SW/SnJ mice did not develop fatal shock, whereas DBA/2J mice did. When dose 3 of antigen (BSA or EA) was postponed to day +21, all mouse strains sensitized by the multiple-dose procedure were found to be susceptible to shock. The fatal shock induced by this procedure, as well as that induced by giving a single sensitizing dose of antigen and Ptx, could be prevented by one to three 1-ml doses of saline given i.v. at the time signs of severe shock appeared. Although only one dose of saline was often sufficient to save the mice, two or three doses were usually needed. Microscopic changes were not found in midsagittal sections of the brains of mice sensitized by either procedure. This was true of mice that died from shock or were saved from shock by injections of saline. From these results, we concluded that the proposed model for encephalopathy induced in mice by Ptx and BSA demonstrates only the well-known anaphylactogenic effect of Ptx or pertussis vaccine. Since there are many other more sensitive methods to detect Ptx, induction of anaphylaxis is not of much value for detection or quantitation of Ptx in pertussis vaccine.
Peroutka SJ; Kitamura K; Lim M; Steinman L Treatment of lethal
pertussis vaccine reaction with histamine H1 antagonists. Neurology, 37: 6, 1987 Jun,
We studied mortality after pertussis immunization in the mouse. Without treatment, 73 of 92 animals (80%) died after injection of bovine serum albumin (BSA) on day +7 of pertussis immunization. After pretreatment with 3 mg of cyproheptadine, 2 mg mianserin, or 2 mg chlorpheniramine, only 5 of 105 animals (5%) died after receiving BSA on day +7 (p less than 0.001). Blockade of histamine H1 receptors may reduce mortality in pertussis immunization-induced encephalopathy in mice.
A murine encephalopathic syndrome can be induced by the administration of BSA and whole-cell pertussis vaccine. The present paper reports studies of the capacity of purified individual pertussis components to induce this effect. Pertussis toxin and endotoxin together with a highly immunogenic sensitizer protein were required to induce the effect. The strength of the antibody response to the sensitizer appeared to be more important than the H-2 type of the recipient in determining the susceptibility of different mouse strains. The relevance of this syndrome to the study of possible vaccine-induced encephalopathy in man is uncertain and requires further investigation.
HC, Mizisin AP, Wiley CA, Morey MK, Hughes RA. Relationship of
adjuvants and swine influenza vaccine to experimental neuropathy in rabbits.Acta Neuropathol (Berl). 1987;73(1):12-8.PMID: 3037840 [PubMed - indexed for
Experimental neuropathy, characterized by endoneurial edema and demyelination, was induced by inoculating rabbits with a combination of Freund's complete adjuvant (FCA), gangliosides, lecithin and cholesterol. A less severe demyelinating neuropathy could be induced by treatment with FCA alone but no significant change could be elicited by injection of swine influenza vaccine (SFV) alone. When FCA was combined with gangliosides, lecithins, cholesterol and SFV, neuropathy occurred, but the changes were less severe than if these agents were used without SFV. Sera were tested for myelin basic protein (MBP) and galactocerebroside (GC) antibodies in each experimental group. Neither SFV alone nor SFV combined with Freund's complete adjuvant, gangliosides, cholesterol and lecithin evoked significant antibody titers to MBP or GC. However, rabbits inoculated with FCA, gangliosides, lecithin and cholesterol had rising titers of antibody to both MBP and GC over the 3-month experimental period. One rabbit inoculated with FCA alone had significant antibody to MBP. The findings suggest that Freund's complete adjuvant alone can induce demyelination in the peripheral nerves of rabbits and that SFV may modulate the immune response acting either as an adjuvant or suppressant in the experimental demyelinating disease.