Comparison of adjuvants for immune potentiating properties and side effects in mice.
Four types of adjuvants were evaluated as alternatives to the use of Freund's complete adjuvant in mice. The adjuvants evaluated included a water-in-oil emulsion (Specol), a microorganism (Lactobacillus), performed immune-stimulating complexes (ISCOM) containing rabies virus glycoprotein and a saponin, Quil A. The adjuvants and saline were combined with three weak immunogens (a synthetic peptide, a self antigen and a particulate antigen) and given by three different routes (intraperitoneal, subcutaneous and dorsal in the foot). The evaluation was based on clinical observations, behavioural studies, pathological lesions and capacity to support immunological responses to weak immunogens. Lesions were most severe after injection of antigen combined with Freund's adjuvant or Quil A, mild to moderate with Specol and minimal with Lactobacillus, iscom conjugates or saline. Despite pathological changes, no signs of prolonged pain or distress could be demonstrated based on clinical observations and behavioural studies. Minimal immunological responses were found after injection of antigen in combination with saline or Lactobacillus. T-cell activation and high antibody responses were found after injection of antigen-iscom conjugates or antigen in Freund's adjuvant emulsions. After Specol/antigen immunisations T-cell activation was demonstrated and high antibody titres were found except for Specol/self antigen immunisations. Presented data suggest that Specol is a possible alternative to Freund's complete adjuvant for the induction of an immune response against weak immunogens except possibly self antigens, for which performed iscoms seem very suitable.
National Institute of Public Health and Environmental Protection (RIVM), Bilthoven, The Netherlands.
P P
PP
Leenaars
C F
CF
Hendriksen
M A
MA
Koedam
I
I
Claassen
E
E
Claassen
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology*; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D001522:Behavior, Animal / Q000187:drug effects; D005260:Female; D006614:Hindlimb; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D007422:Intestines; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010538:Peritonitis / Q000473:pathology; D012704:Serous Membrane / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology
D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial