Ppam. Leenaars et al., ASSESSMENT OF SIDE-EFFECTS INDUCED BY INJECTION OF DIFFERENT ADJUVANTANTIGEN COMBINATIONS IN RABBITS AND MICE/, Laboratory animals, 32(4), 1998, pp. 387-406
We evaluated the side effects induced by injection of Freund's adjuvan
t (FA) and alternative adjuvants combined with different antigens. Rab
bits and mice were injected subcutaneously, intramuscularly (rabbits)
and intraperitoneally (mice) with different adjuvants (FA, Specol, RIB
I, TiterMax, Montanide ISA50) in combination with several types of ant
igens (synthetic peptides, autoantigen, glycolipid, protein, mycoplasm
a or viruses). The effects of treatment on the animals' well-being wer
e assessed by clinical and behavioural changes (POT and LABORAS assays
) and gross and histopathological changes. In rabbits, treatment did n
ot appear to induce acute or prolonged pain and distress. Mice showed
behavioural changes immediately after (predominantly secondary) immuni
zation. Injection of several adjuvant/antigen mixtures resulted in sev
ere pathological changes, depending on adjuvant, type of antigen, anim
al species used and route of injection. Both rabbits and mice showed p
athological changes ranging from marked to severe after injection of F
A, and ranging from minimal to marked after Specol and Montanide injec
tions. Pathological changes after RIBI injections were severe in rabbi
ts, though slight in mice. After TiterMax injections, pathological cha
nges were moderate in rabbits, though severe in mice. In conclusion, i
njection of FA according to present guidelines resulted mostly in seve
re pathological changes, whereas only very few clinical and behavioura
l signs indicated prolonged severe pain. Our findings indicate that Mo
ntanide ISA50 and Specol induce acceptable antibody titres, and cause
fewer pathological changes than FA. Thus they are effective alternativ
es to FA.