ALKYL-ESTERS OF POLYACRYLIC-ACID AS VACCINE ADJUVANTS

Previously, we demonstrated that polyacrylic acid (PAA) augmented sign ificantly the immune response to inactivated Newcastle disease virus ( iNDV) in chickens, but that efficacy was insufficient to replace the w ater-in-mineral oil (W/O) adjuvant applied for boosting primed animals . Attempting to improve its adjuvanticity, PAA with weight-average mol ecular weight (M-w) of 450 kDa was grafted with alkyl-chains by esteri fying the carboxylic groups with octanol and butanol. The butyl-PAA an d octyl-PRA esters obtained varied in degree of esterification between 10% and 92%. Adjuvant activity of water-soluble esters for humoral re sponses to iNDV was examined in chickens primed previously with iNDV w ithout adjuvant. The alkyl-PAA esters exhibited significantly higher r esponses than unmodified PAA and titres increased with increasing dose of adjuvant. At doses of 2 mg per animal, octyl- and butyl-PAA esters with a substitution rate of 16% (octyl16-PAA and butyl16-PAA, respect ively) gave similar titres as W/O. In aged animals primed with live ND V at early age, butyl16-PAA and W/O elicited comparable antibody respo nses. Butyl16-PAA was also more effective than PAA in stimulating prim ary immune responses in mice which was accompanied by stronger local r eaction determined by monitoring swelling at the site of injection. Re actogenicity of butyl16-PAA was less than of W/O. We concluded that al kyl-PAA esters are strong adjuvants for primary and secondary response s and that they are promising alternatives to the mineral oil-based ad juvants presently used in various veterinary vaccines. (C) 1998 Elsevi er Science Ltd. All rights reserved.