Comparison of adjuvants for immune potentiating properties and side effects in mice
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Series / Report no.
Open Access
Type
Report
Language
en
Date
1994-09-30
Research Projects
Organizational Units
Journal Issue
Title
Comparison of adjuvants for immune potentiating
properties and side effects in mice
Translated Title
Vergelijking van adjuvantia voor immuunstimulerend
effect en bijwerkingen in muizen
Published in
Abstract
Vier typen adjuvantia zijn geevalueerd als alternatief
voor het gebruik van Freund's compleet adjuvant in muizen. De volgende
adjuvantia zijn geevalueerd: een water-in-olie emulsie (Specol), een
micro-organisme (Lactobacillus), een immuunstimulerend complex met ingebouwd
glycoproteine van rabies virus (RV-iscoms) en een saponine. Quil A. De
adjuvantia en controle groepen (fysiologisch zout) zijn gecombineerd met
drie zwak immunogene antigenen (een synthetisch antigeen, een autoantigeen
en een deeltjes antigeen) en ingespoten via drie routes (intraperitoniaal,
subcutaan en op de dorsale zijde van de achterpoot. De evaluatie is
gebaseerd op klinische oobservaties, gedragsstudies, pathologische
bevindingen en immunostimulatie. Lesies zijn het ernstigst na inspuiten van
antigeen in Freund's adjuvant of Quil A, gering tot matig in combinatie met
Specol en minimaal na Lactobacillus, RV-iscoms of fysiologisch zout.
Ondanks de ernstige pathologische veranderingen, konden geen signalen van
blijvende pijn of ongerief bij de dieren worden aangetoond aan de hand van
klinische bevindingen en gedragsstudies. De immuunresponsen zijn zeer laag
na inspuiten van antigeen in combinatie met fysiologisch zout of
Lactobacillus. T-cel activatie en hoge antilichaam responsen zijn gevonden
na inspuiten van antigeen/RV-iscoms conjugaten en na inspuiten van
antigeen/Freund's adjuvant emulsies. T-cel activatie is aangetoond na
inspuiten van antigeen/Specol emulsies en antilichaam responsen zijn hoog
behalve na inspuiten van Specol in combinatie met autoantigeen. de gevonden
resultaten suggereren dat Specol een mogelijk alternatief is voor Freund's
compleet adjuvant voor de inductie van een immuunrespons tegen zwak
immunogene antigenen behalve tegen autoantigenen, hiervoor lijkt RV-iscom
een geschikt alternatief adjuvant.
Four types of adjuvants were evaluated as alternative to the use of Freund's complete adjuvant in mice. The evaluation was based on clinical observations, behavioural and physiological state, gross and histo-pathological lesions and capacity to support immunological responses to weak immunogens. The adjuvants included water-in-oil emulsion containing Mycobacteria (Freund's complete adjuvant; substituted for Freund's incomplete adjuvant in booster immunization), a water-in-oil emulsion (Specol), a micro-organism (Lactobacillus), preformed immune-stimulating complexes containing rabies virus glycoprotein and a saponin, Quil A. The adjuvants were combined with three types of weak immunogens including: a synthetic peptide, an 'auto'antigen (myelin basic protein) and a particulate antigen (inactivated Mycoplasma pneumoniae). Each adjuvant/antigen preparation was injected (primary and booster) either intraperitoneally (i.p.), subcutaneously in the neck or groin (s.c.) or subcutaneously at the dorsal side of the hind feet. The injection of adjuvant/antigen preparations resulted in most severe pathological lesions, including granulomatous peritonitis and tissue necrosis, after administration of Freund's adjuvant/antigen or Quil A/antigen mixtures. Injection of Specol/antigen had mild to moderate inflammatory effects, while injection of Lactobacillus/antigen or antigen-iscom conjugates caused minimal side effects. Lesions were most frequently seen after injection of Mycoplasma pneumoniae preparations where i.p. injection resulted in relatively severe pathological changes as compared to s.c. injection. Despite these pathological changes, no signs of prolonged pain or distress could be demonstrated based on clinical observations and physiological and behavioural parameters. Minimal antibody responses and T-cell activation 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. T-cell activation was demonstrated after Specol/antigen immunizations and high antibody titers were found except for Specol/'auto'antigen immunizations. In studying adjuvant activity the influence of type of antigen, on side effects and immune response, should be taken into account. Despite severe inflammatory lesions found at necropsy after injection of Freund's adjuvant/antigen no prolonged signs of pain and distress could be detected. 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 autoantigens, for which preformed iscoms seem very well suitable.
Four types of adjuvants were evaluated as alternative to the use of Freund's complete adjuvant in mice. The evaluation was based on clinical observations, behavioural and physiological state, gross and histo-pathological lesions and capacity to support immunological responses to weak immunogens. The adjuvants included water-in-oil emulsion containing Mycobacteria (Freund's complete adjuvant; substituted for Freund's incomplete adjuvant in booster immunization), a water-in-oil emulsion (Specol), a micro-organism (Lactobacillus), preformed immune-stimulating complexes containing rabies virus glycoprotein and a saponin, Quil A. The adjuvants were combined with three types of weak immunogens including: a synthetic peptide, an 'auto'antigen (myelin basic protein) and a particulate antigen (inactivated Mycoplasma pneumoniae). Each adjuvant/antigen preparation was injected (primary and booster) either intraperitoneally (i.p.), subcutaneously in the neck or groin (s.c.) or subcutaneously at the dorsal side of the hind feet. The injection of adjuvant/antigen preparations resulted in most severe pathological lesions, including granulomatous peritonitis and tissue necrosis, after administration of Freund's adjuvant/antigen or Quil A/antigen mixtures. Injection of Specol/antigen had mild to moderate inflammatory effects, while injection of Lactobacillus/antigen or antigen-iscom conjugates caused minimal side effects. Lesions were most frequently seen after injection of Mycoplasma pneumoniae preparations where i.p. injection resulted in relatively severe pathological changes as compared to s.c. injection. Despite these pathological changes, no signs of prolonged pain or distress could be demonstrated based on clinical observations and physiological and behavioural parameters. Minimal antibody responses and T-cell activation 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. T-cell activation was demonstrated after Specol/antigen immunizations and high antibody titers were found except for Specol/'auto'antigen immunizations. In studying adjuvant activity the influence of type of antigen, on side effects and immune response, should be taken into account. Despite severe inflammatory lesions found at necropsy after injection of Freund's adjuvant/antigen no prolonged signs of pain and distress could be detected. 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 autoantigens, for which preformed iscoms seem very well suitable.
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VHI
RIVM
TNO/PG Rijswijk