Japanese encephalitis (JE) vaccine has been used in childhood immunization programmes in Asia for many years. Also travellers from other parts of the world have been vaccinated before travelling in Asian countries. Recommendations for the use of JE vaccine are still debated because severe cases of adverse reactions have been reported. In Denmark an inactivated JE vaccine derived from infected mouse brain has been used and 350000 doses have been distributed from the Statens Serum Institut since 1983. In the period 1983-1995, 101 adverse reactions after JE vaccination have been registered including 73 allergic mucocutaneous reactions. These reactions have occurred each year since 1989 with frequencies varying from 1-17 per 10,000 vaccinees. The highest frequencies and the most serious reactions acquiring hospitalization were seen in the period 1989-1992. Three batches (EJN 012, 033 and 048) distributed before 1992 caused the highest number of reactions but all batches delivered in Denmark since 1989 have caused reactions. Therefore, it is still very important to collect information on adverse events as well as information of the risk of acquiring JE infection in order to give sound recommendations to travellers.
In recent years, there has been a remarkable increase in measles cases among preschool and secondary school children in Turkey, as in many other countries. The seroconversion and coverage rates of measles vaccine should therefore be evaluated in order to obtain data that could be used to determine the vaccination policy for Turkey. Measles immunity status was studied by an enzyme-linked immunosorbent (ELISA) test determining the anti-measles IgG antibody levels. Measles specific IgG antibodies were found to be positive in 77.88% of the entire study group of 800 children aged 11 months to 12 years, while 21.25% had negative sera. Seven (0.87%) subjects had borderline results. The results of this study indicate the need to administer a second dose of measles vaccine, preferably at 18 months of age concomitant with other vaccines. This vaccination policy, together with an increase in the extent of immunization coverage, may help to achieve the World Health Organization's (WHO) target of the complete eradication of measles.
We studied the biologic activity of allergen preparations using a method involving skin prick tests in humans and the use of HEP (histamine equivalent prick) units. Results were found to be dependent on the population groups used in assays. If populations are not carefully standardized, results may vary by 1 power of 10. Accuracy can also be improved by the use of suitable allergen standard reference preparations, but such were not available to us. Confidence ranges for the biologic activities were relatively wide and varied with the allergen preparation and the population group. Typically, the 95% confidence range included values from one-fifth to five times the estimated HEP value when the number of subjects in the assay was 30 to 50 persons. When the preparations representing the same source material (e.g., timothy pollen) were assayed simultaneously in one population group of this size, a twofold or larger difference in HEP values generally proved significant. An examination of 43 commercial products showed that allergen preparations with biologic activities declared in HEP units had a more uniform biologic activity than those assayed with traditional methods and units (PNU/ml or weight/volume).
Feeding a soluble antigen to an animal is known to cause a state of unresponsiveness against this antigen. If this antigen is given together with another antigen during the sensitization procedure, impairment of the response to the new antigen can also be seen, a phenomenon referred to as bystander suppression. The induction of tolerance against ovalbumin (OvA) and the effect of bystander suppression on the response to the hapten trimellitic anhydride (TMA), a cause of occupational asthma, were studied in Brown-Norway rats. Rats were fed either OvA-containing pellets or standard diet for 16 days before sensitization with the mixture of TMA and OvA. The animals were followed for 6 weeks after sensitization. Animals made tolerant to OvA showed a significantly suppressed delayed-type hypersensitivity (DTH) reaction against both OvA and TMA compared with the nontolerized control group at 5 weeks after sensitization, implying bystander suppression. By contrast, immunoglobulin (Ig)E and IgG antibody levels were suppressed only against OvA, whereas anti-TMA antibody levels were not affected. Airway eosinophilia after a single aerosol challenge at 6 weeks after sensitization using TMA conjugated to rat serum albumin, correlated with IgE anti-TMA levels in the group made tolerant to OvA and was not affected by OvA ingestion. In conclusion, suppressive factors released in ovalbumin-tolerant rats when they are challenged with ovalbumin, can suppress the response to trimellitic anhydride and this suppression is more pronounced for T-helper1-type responses.
Bronchial responsiveness to inhaled acetylcholine (ACh) and inflammatory cell recruitment in bronchoalveolar lavage fluid (BALF) were studied in inbred Brown-Norway rats actively sensitized to, and later exposed to, ovalbumin (OA). We examined animals 21 days after initial sensitization at 18 to 24 hours, or 5 days after a single challenge, or after the last of seven repeated exposures administered every 3 days. BALF was examined as an index of inflammatory changes within the lung. Animals repeatedly exposed to OA aerosols had an increased baseline lung resistance and a significant increase in bronchial responsiveness to inhaled ACh compared to control animals at both 18 to 24 hours and 5 days after the last OA exposure. Sensitized animals receiving a single OA aerosol also demonstrated bronchial hyperresponsiveness (BHR) to inhaled ACh (p less than 0.01) at 18 to 24 hours of a similar order as the multiple-exposed group. There was a significant increase in eosinophils, lymphocytes, and neutrophils in BALF at 18 to 24 hours but not at 5 days after single or multiple exposure to OA aerosol in the sensitized groups. Control animals demonstrated no changes in bronchial responsiveness, although a small but significant increase in inflammatory cells was observed compared to saline-only treated animals. There was a significant correlation between bronchial responsiveness and eosinophil counts in the BALF in the single allergen-exposed group (Rs = 0.68; p less than 0.05). We conclude that (1) BHR after allergen exposure in sensitized rats is associated with the presence of pulmonary inflammation but persists despite the regression of inflammatory cells in BALF after multiple OA exposures, and (2) this rat model has many characteristics of human allergen-induced BHR.
The objective of the present study was to characterize the antigenic specificity of purified soybean beta-conglycinin and to investigate its effects on the growth and immune responses of rats. Thirty-two Brown Norway rats, 3 weeks of age, were randomly allotted to one of four treatments and individually fed casein-cornstarch based diets. Rats were sensitised by means of intragastric gavage with purified beta-conglycinin (0, 5, 10 or 20 mg protein/ml in phosphate buffered saline at pH 7.4) on day 0, 7, 14, and 21 (1 ml/animal). On day 28, rats received a double dose of beta-conglycinin. Blood was obtained at weekly intervals after initiation of challenge. Growth declined linearly with increasing the concentration of soybean beta-conglycinin (p
BACKGROUND: Soybean is a relevant allergenic food, but little is known about individual threshold doses in soy allergy. OBJECTIVE: We sought to determine the clinical characteristics of soy allergy in Europe, including a dose-response curve. METHODS: Patients with a history of soy allergy underwent a titrated, double-blind, placebo-controlled food challenge. A statistical model was used to calculate the risk of allergic consumers to experience an allergic reaction to soy. Sera were analyzed for specific IgE to soy, peanut, Bet v 1, and Gly m 4. RESULTS: All patients but one responded primarily with subjective symptoms to the challenge followed by objective symptoms in 11 subjects, ranging from rhinitis up to a decrease in blood pressure. Cumulative threshold doses for allergic reactions ranged from 10 mg to 50 g for subjective symptoms and from 454 mg to 50 g for objective symptoms. The pattern of IgE reactivity against proteins with molecular weights of between approximately 10 and 70 kd was highly individual among the patients and did not correlate with the severity of symptoms. CONCLUSIONS: When data are fitted by using a normal distribution statistical model, they predict that 1% of patients with soy allergy would react subjectively and objectively with 0.21 and 37.2 mg of soy protein, respectively. CLINICAL IMPLICATIONS: Both the clinical and immunologic basis of soy allergy in Europe are highly complex, which affects the diagnosis of soy allergy and the advice given to patients with soy allergy in regard to risk management.
Arctic Investigations Program, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Public Health Service, United States Department of Health and Human Services, Anchorage, AK.
We compared the immunogenicity of the four available Haemophilus influenzae type b (Hib) conjugate vaccines in Alaska Native infants. Three of the vaccines, Hib oligosaccharide-CRM197 (HbOC), polyribosylribitol phosphate-diphtheria toxoid (PRP-D) and polyribosylribitol phosphate-tetanus toxoid (PRP-T), were given at 2, 4 and 6 months of age, and the PRP Neisseria meningitidis outer membrane protein (PRP-OMP) conjugate vaccine was given at 2 and 4 months of age. Enrollment was largely sequential by vaccine availability beginning with HbOC and ending with PRP-T. A total of 225 infants completed the full vaccination series. Groups of infants receiving the different vaccines did not differ significantly by sex, ethnicity, degree Alaska Native or age at vaccination. The only vaccine that induced a response with the first 2-month dose was PRP-OMP; 91% of infants had > or = 0.15 micrograms/ml and 57% had > or = 1.0 microgram/ml of anti-PRP antibody by 4 months of age. After two doses it also remained the most immunogenic. After the full three vaccine series, trials that requires cough of 21 days is excessively restrictive.
The hepatic cytochrome P4502A6 (CYP2A6) enzyme mediates the oxidative metabolism of several procarcinogens that have liver as their primary target. Mouse models indicate that liver tumors invariably overexpress CYP2A forms, and that inflammation and cirrhosis may regulate the CYP2A expression pattern. In this study, the distribution of the CYP2A6 protein was investigated in a series of 24 human hepatocellular carcinoma (HCC) samples by immunohistochemical analysis. A polyclonal antibody was raised in chicken against CYP2A5, the mouse orthologue of CYP2A6. The antibody was characterized and found to be specific for CYP2A members. In DBA/2 mouse liver, a strong increase of CYP2A5 protein amount, localized in the perivenous region, occurred in response to treatment with pyrazole. In human HCC samples, overexpression of CYP2A6 protein was associated with the presence of chronic inflammation and cirrhosis. CYP2A6 protein was observed in 9 of 16 (56%) of samples with non-neoplastic hepatocytes and in 10 of 24 (42%) HCC samples. The staining for CYP2A6 protein was very heterogeneous in tumor cells, suggesting that increased expression of CYP2A6 occurred in a distinct subpopulation of neoplastic cells. In Kaplan-Meyer survival analysis, there was a tendency toward a more favorable prognosis in patients with CYP2A6-positive tumors in comparison with patients with CYP2A6-negative tumors. These data suggest that, in human HCC, in contrast to mouse liver tumors, CYP2A6 overexpression is not an invariable phenotype.