New adjuvant formulations, based on proteoliposomes <40 nm and cochleates <100 nm, without Al(OH) 3 adjuvant, were evaluated regarding their ability to generate Th1 immune response through a Delayed -Type Hypersensitivity Test, at the mouse model, by using a Neisseria meningitidis B protein complex as antigen. The formulations were administered by intramuscular (IM) (2 inoculations -at baseline and after 14 days) and intranasal (IN) (3 inoculations at 7 days) immunization pathways. All IM immunized groups were able to induce similar response to these formulations as well as to VA-MENGOC-BC® vaccinecontaining Al(OH) 3 adjuvant (used as positive control of the trial). In all groups, the induced inflammation (IP) rate was statistically higher than in the negative control group (CN) (p<0.05). Immunogenicity, measured by HSR and CD4 + lymphocyte increase was equivalent to the control vaccine and most important, granuloma reactogenicity at the site of injection was eliminated, fact demonstrated by histological study. All groups of animals immunized by IN route showed HSR reactions and statistically significant differences with respect to the CN group. However, IP values were lower, with statistical differences (p<0.05) for the same adjuvant formulation IM administered, except the AIF2-nCh formulation that generated statistically similar induction (p>0.05) by both immunization pathways, suggesting it to be the best candidate for the next IN trial. Proteoliposome and cochleate formulations tested were able to mount potent Th-1 immune response, equivalent to the original vaccine formulation, with the advantage of less reactogenicity in the site of the injection, caused by the toxicity of Al(OH) 3 adjuvant gel.

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The proteoliposomes and cochleates are used as adjuvants for vaccines since they are potent immune stimulators. However, the hyper stimulation of the immune system provoked by adjuvants can cause immune-toxicological side effects. The present study was carried out to evaluate the toxic and immuno-toxicological effects of new adjuvants for anti-meningococci vaccines based on neo-proteoliposomes (nPL) and neo-cochleates (nCh), in Balb/c mice that were administered doses of 15 �g each, over periods of 14 days through intramuscular route and three inoculations with the same doses through intranasal route, every 7 days. The Scanning and Transmission Electron Microscopy showed that the nPL and nCh had nanometric dimensions and their normal peculiar forms. The experimental formulations did not provoke general toxic effects in the tested animals, which tended to the progressive normal growing of this species, that did not statistically differ from the control ones. The studies of pathologic anatomy in inoculation organs and sites did not reveal modifications that can indicate toxicity and there was no sign of hepatic damage. The structural observations found in the spleen and lymphatic nodes showed the physiological development of the immune response, which was normal in all cases showing the restitution of the stimulation signs. The relative weight values of the spleen were within the standard range. These results showed that the nPL and nCh elaborated as adjuvants for vaccines did not show any evident induction of general toxic or particular immune-toxicologicl effects.

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Introducción: El ensayo de micronúcleos transplacentario, ha sido desarrollado con el objetivo de evaluar el potencial genotóxico en la descendencia y demostrar la capacidad de un agente de causar daños cromosómicos durante el período prenatal. Éste realiza el registro de aberraciones cromosómicas, demostrando si una sustancia determinada puede ser clastogénica o aneugénica en el feto, a través de la exposición materna.Objetivo: Por lo cual en el presente trabajo se tuvo como objetivo determinar la frecuencia espontánea e inducida de micronúcleos transplacentarios en ratones de la línea Balb/c. Pretendiendo vincular de esta forma el efecto genotóxico y reproductivo de una droga a evaluar por esta metodología.Materiales y métodos: Se formaron 4 grupos experimentales, el primero un control negativo (simulacro), el segundo control solvente NaCl (0,9%), en el tercero se utilizo la ciclofosfamida en dosis de 50 mg/kg, y el cuarto se utilizó la bleomicina en dosis de 20 mg/kg. Todos los grupos se administraron por vía intraperitoneal los días 14, 15 y 16 de la gestación y 24 h después de la última inoculación se procedió al sacrificio de las gestantes por dislocación cervical. Obteniéndose las muestras de médula ósea materna e hígado fetal.Resultados: Se obtuvo como resultado los valores espontáneos e inducidos de los índices de citotoxicidad y de genotoxicidad, así como el total de micronúcleos divididos según niveles de daños.Discusión y conclusiones: Se observo mayor inducción de daño en células hepáticas fetales que en médula ósea materna. Además se demostró que la ciclofosfamida es capaz de inducir mayor citotoxicidad y genotoxicidad que la bleomicina tanto en células de la médula ósea materna como en células hepáticas fetales. Por tanto se demostró el poder clastogénico transplacentario de ambos mutágenos vinculando este ensayo de genotoxicidad a la reproducción. Además estos resultados se pudieran utilizar en la evaluación de nuevas drogas con carácter antigenotóxico por vía transplacentaria.