Alkyl-polyacrylate esters are strong mucosal adjuvants

Synthetic polymers were examined for their potency to enhance mucosal immun e responses to inactivated antigens. Aqueous solutions of polyacrylic acid with a MW of 450 kDa (p[AA]) or an butyl-ester thereof with 16% esterificat ion (Butyl16-p[AA]) plus antigen were administered twice intranasally in mi ce with a 2 week interval. The frequency of IgA-antibody secreting cells (A SCs) in lung cell suspensions was determined 1 week after the second immuni sation. Both polymers significantly enhanced the IgA response against inact ivated Newcastle disease virus (iNDV), inactivated influenza virus strain M RC-11 (iMRC-11), haemagglutinin/neuraminidase subunits of influenza virus s train A/Texas (HA/NA) and bovine serum albumin (BSA). Butyl16-p(AA) was sig nificantly more effective than non-derivatised p(AA), cholera toxin B subun it (CTB) or liposomes. The factor of increase in IgA-ASCs varied from < 10- to > 100-fold and depended on the type of antigen, the dose of antigen and the adjuvant. Extremely high responses of about 10,000 IgA-ASCs per millio n lung cells were detected after immunisation with 5 mu g HA/NA plus 50 mu g Butyl16-p(AA). Intranasal immunisation with Butyl16-p(AA) resulted in hig h IgA responses, not only in the lungs, but also in the spleen and in high IgG responses in these organs. We concluded that alkyl-esters of polyacryla te are an interesting, novel category of mucosal adjuvants. (C) 2000 Elsevi er Science Ltd. All rights reserved.