Clinicopathological studies in lambs repetitively inoculated with products containing alimunium adjuvants

Abstract

The use of aluminum-containing vaccine adjuvants is widespread in the Spanish small ruminant industry. These compounds were related to an episode of vaccine adverse reactions which gave rise to a process known today as the ovine ASIA syndrome.

An in vivo model of this syndrome was established. Eighty-four lambs were selected, divided into three groups (n=28 each) and submitted to an intensive inoculation program with: i) Vaccines containing aluminum hydroxide as adjuvant; ii) The adjuvant only; iii) PBS. Nineteen inoculations were performed during 15 months. A comprehensive in vivo follow-up was performed, including clinical examinations and behavioral and cognitive tests. After euthanasia, the pathology of different tissues was studied grossly, microscopically and by electron microscopy. The presence of aluminum in tissues was studied by energy dispersive X-ray spectroscopy, graphite furnace atomic absorption spectroscopy and lumogallion fluorescent staining.

Animals in the vaccinated and adjuvant-inoculated groups presented persistent injection-site granulomas with intramacrophagic aluminum. Persistency was higher in the vaccinated group (p<0.001), reaching 15 months in some cases. There was translocation of aluminum to the regional lymph nodes (p<0.001) and lumbar spinal cord (p<0.001). Vaccinated and adjuvant-inoculated animals showed an increase in aggressive interactions (p<0.001) and stereotypies (p<0.001) and a decrease in affiliative interactions (p<0.001) when compared with the control group. Differences were more marked with higher number of doses applied.

Repetitive inoculation of aluminum-hydroxide only or combined into commercial vaccines to experimental lambs induces highly persistent injection site granulomas, accumulation of aluminum in distant tissues and changes in the inter-individual interaction patterns.