Alkyl-esters of polyacrylic acid as vaccine adjuvants

Previously, we demonstrated that polyacrylic acid (PAA) augmented significantly the immune response to inactivated Newcastle disease virus (iNDV) in chickens, but that efficacy was insufficient to replace the water-in-mineral oil (W/O) adjuvant applied for boosting primed animals. Attempting to improve its adjuvanticity, PAA with weight-average molecular weight (Mw) of 450 kDa was grafted with alkyl-chains by esterifying the carboxylic groups with octanol and butanol. The butyl-PAA and octyl-PAA esters obtained varied in degree of esterification between 10% and 92%. Adjuvant activity of water-soluble esters for humoral responses to iNDV was examined in chickens primed previously with iNDV without adjuvant. The alkyl-PAA esters exhibited significantly higher responses 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, respectively) gave similar titres as W/O. In aged animals primed with live NDV at early age, butyl16-PAA and W/O elicited comparable antibody responses. Butyl16-PAA was also more effective than PAA in stimulating primary immune responses in mice which was accompanied by stronger local reaction determined by monitoring swelling at the site of injection. Reactogenicity of butyl16-PAA was less than of W/O. We concluded that alkyl-PAA esters are strong adjuvants for primary and secondary responses and that they are promising alternatives to the mineral oil-based adjuvants presently used in various veterinary vaccines.