Immuno-toxicological evaluation of the adjuvant formulations for experimental anti-meningococcal vaccines without aluminium hydroxide

Abstract

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 µg 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.