Enhanced mucosal priming by cholera toxin and procholeragenoid with a lipoidal amine adjuvant (avridine) delivered in liposomes

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Abstract
The mucosal adjuvant activity of avridine, a synthetic lipoidal amine [N,N-dioctadecyl-N',N'-(2-hydroxymethyl) propanediamine, previously designated CP-20,961), was studied in rats immunized intraintestinally with cholera toxin or procholeragenoid. Avridine was most efficient as an adjuvant when incorporated into liposomes; liposomes that lacked avridine had no adjuvant effect. Coadministration of avridine-containing liposomes with enteric priming doses of cholera toxin or procholeragenoid enhanced the efficiency of priming for secondary mucosal anti-cholera toxin responses, i.e., the establishment of memory, five- to sevenfold. Avridine-containing liposomes had no significant effect, however, on either the primary mucosal anti-cholera toxin response, when given with the primary dose of antigen, or on the secondary response, when given with the booster dose to previously primed animals. Little or no adjuvant effect occurred when avridine-containing liposomes were given concurrently with antigen, but at a separate mucosal site or parenterally, or at the site of enteric immunization, but 1 day earlier or later. These results support the notion that adjuvants may be developed which enhance the mucosal immunogenicity of locally applied antigens and suggest that liposomes may be effective vehicles for delivery of such adjuvants.