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Cytokines expression from altered motor thalamus and behavior deficits following sublethal administration of Shiga toxin 2a involve the induction of the globotriaosylceramide receptor

2022-09-01T00:00:00Z

Title: Cytokines expression from altered motor thalamus and behavior deficits following sublethal administration of Shiga toxin 2a involve the induction of the globotriaosylceramide receptor Authors: Arenas-Mosquera, David; Pinto, Alipio; Cerny, Natacha; Berdasco, Clara; Cangelosi, Adriana; Geoghegan, Patricia A.; Malchiodi, Emilio Luis; De Marzi, Mauricio C; Goldstein, Jorge Abstract: Encephalopathy associated with hemolytic uremic syndrome is produced by enterohemorrhagic E. coli (EHEC) infection, which releases the virulence factors Shiga toxin (Stx) and lipopolysaccharide (LPS). Neurological compromise is a poor prognosis and mortality factor of the disease, and the thalamus is one of the brain areas most frequently affected. We have previously demonstrated the effectiveness of anti-inflammatory drugs to ameliorate the deleterious effects of these toxins. However, the thalamic production of cytokines involved in pro-inflammatory processes has not yet been acknowledged. The aim of this work attempts to determine whether systemic sublethal Stx2a or co-administration of Stx2a with LPS are able to rise a proinflammatory profile accompanying alterations of the neurovascular unit in anterior and lateral ventral nuclei of the thalamus (VA-VL) and motor behavior in mice. After 4 days of treatment, Stx2a affected the lectin-bound microvasculature distribution while increasing the expression of GFAP in reactive astrocytes and producing aberrant NeuN distribution in degenerative neurons. In addition, increased swimming latency was observed in a motor behavioral test. All these alterations were heightened when Stx2a was co-administered with LPS. The expression of pro-inflammatory cytokines TNFα, INF-γ and IL-2 was detected in VA-VL. All these effects were concomitant with increased expression of the Stx receptor globotriaosylceramide (Gb3), which hints at receptor involvement in the neuroinflammatory process as a key finding of this study. In conclusion, Stx2a to Gb3 may be determinant in triggering a neuroinflammatory event, which may resemble clinical outcomes and should thus be considered in the development of preventive strategies.

Pertussis whole cell vaccine: relation between intracerebral protection in mice and antibody response to pertussis toxin, filamentous hemagglutinin and adenylate cyclase

1992-06-01T00:00:00Z

Title: Pertussis whole cell vaccine: relation between intracerebral protection in mice and antibody response to pertussis toxin, filamentous hemagglutinin and adenylate cyclase Authors: Dellepiane, N I; Manghi, M A; Eriksson, P V; di Paola, G; Cangelosi, Adriana Abstract: N:NIH mice were vaccinated according to the WHO recommendations for the potency test with the Second International Standard for Pertussis Vaccine (ISPV). Blood for serological investigation was taken from the animals on day 14 post immunization before intracerebral challenge with Bordetella pertussis 18323 was done. The relationship between anti-pertussis toxin, anti-filamentous hemagglutinin and anti-adenylate cyclase antibody levels as measured by ELISA and protection from intracerebral challenge was studied. The proportion of surviving mice increased in correlation with increasing anti-PT titres; a protective level of 4 ELISA units/ml was found. Such relationship between protection against intracerebral challenge and antibody titres was not found for anti-FHA nor for anti-AC antibodies, thus suggesting that these antibodies do not play an important role in protection in this model. The excellent correlation between anti-PT antibody titres and protection suggests that the measure of anti-PT response could be a useful tool for estimating the potency of whole-cell vaccines. The development of an alternative method for testing the potency of pertussis whole-cell vaccines based on the anti-PT response should be considered. Description: Fil: Dellepiane, N. I.; Fil: Manghi, M A. Hospital General de Niños “Pedro de Elizalde,” (1270) Buenos Aires; Argentina.; Fil: Eriksson, P V. Instituto de Estudios de la Inmunidad Humoral (CONICET-UBA), Facultad de Farmacìa y Bioquímica, Universidad de Buenos Aires; Argentina.; Fil: di Paola, G.; Fil: Cangelosi, Adriana. ANLIS Dr.C.G.Malbrán. Centro Nacional de Control de Calidad de Biológicos; Argentina.

Development of an ELISA for measuring the activity of tetanus toxoid in vaccines and comparison with the toxin neutralization test in mice

1994-01-12T00:00:00Z

Title: Development of an ELISA for measuring the activity of tetanus toxoid in vaccines and comparison with the toxin neutralization test in mice Authors: Manghi, M A; Pasetti, M F; Brero, María Luisa; Deluchi, Silvana; di Paola, G; Mathet, V; Eriksson, P V Abstract: An enzyme-linked immunosorbent assay (ELISA) has been developed to measure anti-tetanus toxoid antibody levels in immunized guinea-pig sera as a useful alternative to the currently used toxin neutralization test (TNT) in determining the activity of the tetanus toxoid in vaccines. The ELISA was found to measure antibody levels as low as 5.8 x 10(-5) IU/ml. Furthermore, a comparison of the results from ELISA and TNT involving 132 different commercial vaccines showed a very good correlation (r = 0.94, p < 0.001) between antibody levels measured by both methods. The results suggest that the proposed ELISA is a reliable, simple and economical alternative to the TNT in mice for assessing the activity of tetanus toxoids in vaccines.

Development of an alternative method for testing the immunogenicity of diphtheria vaccines

1995-04-01T00:00:00Z

Title: Development of an alternative method for testing the immunogenicity of diphtheria vaccines Authors: Manghi, M A; Pasetti, M F; Brero, María Luisa; Deluchi, Silvana; di Paola, G; Mathet, V; Eriksson, P V Abstract: The immunogenicity of the diphtheria component of 73 commercial vaccines from five different manufacturers was tested by the toxin neutralization test (TNT) and the enzyme-linked immunosorbent assay (ELISA) developed in our laboratory. A comparison of the antibody levels measured by both assays showed a very good correlation (r = 0.95, p < 0.001). The results suggest that the proposed ELISA is a reliable, simple and economical alternative to the TNT in guinea pigs. Also, the ELISA was found to measure IgG antibody levels as low as 5.5 x 10(-5) IU ml-1. To evaluate the possibility of accelerating the active immunization during the activity test of vaccines, an alternative schedule using one single human dose was assayed. A very good correlation was observed between the IgG antibody response obtained with this schedule and with the traditional programme. Therefore, the cost and the time required to perform the activity test may be considerably reduced when both the rapid immunization schedule and the ELISA are used.