CONVERSION OF ORALLY INDUCED SUPPRESSION OF THE MUCOSAL IMMUNE-RESPONSE TO OVALBUMIN INTO STIMULATION BY CONJUGATING OVALBUMIN TO CHOLERA-TOXIN OR ITS B-SUBUNIT

Oral pretreatment of mice with ovalbumin (OVA) not only suppressed a subsequently induced systemic immune response ('oral tolerance') but also suppressed, even more effectively, a subsequently induced intestinal IgA response. In contrast, pretreatment with OVA conjugated to cholera toxin (CT) or its B subunit (CTB) resulted in a stimulative effect. The stimulative effect was enhanced when unconjugated OVA and polymerized OVA were removed from the OVA-CT(B) conjugate mixtures by affinity chromatography, Thus, the effect of oral pretreatment depends on the balance between tolerizing and stimulating components in the conjugate mixture. As OVA-CTB conjugates were at least as effective as OVA-CT conjugates in stimulation of the intestinal immune response, we concluded that the ability of the OVA conjugates to bind to the intestinal mucosa is a prerequisite in inducing the stimulative effect. These observations further demonstrate that conjugation of a protein antigen to an appropriate carrier can convert the nature of the immunization from suppressive into stimulative.