The establishment of endotoxin limits which satisfy animal welfare considerations in the testing of porcine vaccines

Endotoxin (lipopolysaccharide, LPS) is a constituent of the cell walls of g ram-negative bacteria and is found in many vaccines produced from these bac teria. High levels of endotoxin can give rise to a range of pathophysiologi cal reactions, and adverse reactions tend to be seen in animals following v accination. In this study, pigs of various ages and weights were vaccinated with licens ed porcine vaccines and the endotoxin content of the vaccines was determine d with the LAL, conducted according to EP (European Pharmacopeia). The expe riments followed the EP guidelines relating to the safety testing of veteri nary vaccines. The animals were monitored for 48 h after vaccination, their body temperatures were measured, and blood samples were taken for analysis and for the determination of plasma endotoxin levels. There was a clear relationship between vaccine endotoxin content and change s in blood cell counts and in the clinical picture. Elevated plasma endotox in levels correlated with the occurrence of initial leucopenia followed by leucocytosis as well as with clinical symptoms ranging from refusal of food and depression to shock-like symptoms. After 24 h, normal physiological va lues were regained Young animals weighing between IO and 40 kg were found t o be very sensitive to elevated endotoxin content in vaccines. The differen ces in individual reactions could be due not only to differences in vaccine endotoxin content, but also to differences in the reactivity of the organi sm, and in the type of bacteria used or in the composition of the vaccine.