Long-term studies in subcutaneous reactions following inoculation with aluminium-containing products in sheep

In sheep, aluminium in vaccines is related to local inflammatory reactions whose evolution is generally monitored for just a few months to assess vaccine safety. In order to study these reactions and their long-term evolution three groups (n=28 each) of three-month-old lambs were used. Group A was subcutaneously inoculated with aluminium hydroxide-containing vaccines, Group B received the adjuvant alone with equal amount of Al3+ and Group C received PBS. A total of 19 inoculations were performed in 15 months in each group. Local reactions were periodically assessed in vivo by palpation. Post mortem studies included gross and microscopic pathology, microbiology, scanning transmission electron microscopy (STEM) and energydispersive X-ray (EDX) spectroscopy. Reactions consisted in sterile foreign body granulomas, they appeared in vaccinated (100%) and aluminium-inoculated (85.7%) animals and they were more severe and persistent in vaccinated animals. Reactive macrophages in granulomas contained aggregates of a spiculated material that was identified as aluminium. In sheep aluminium-induced granulomas are persistent and accumulate to previous vaccinations. These persistent granulomas might be related to some of the previously-described adverse events included in the ovine ASIA syndrome.