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 s ubsequently induced systemic immune response ('oral tolerance') but al so suppressed, even more effectively, a subsequently induced intestina l IgA response. In contrast, pretreatment with OVA conjugated to chole ra toxin (CT) or its B subunit (CTB) resulted in a stimulative effect. The stimulative effect was enhanced when unconjugated OVA and polymer ized OVA were removed from the OVA-CT(B) conjugate mixtures by affinit y chromatography, Thus, the effect of oral pretreatment depends on the balance between tolerizing and stimulating components in the conjugat e mixture. As OVA-CTB conjugates were at least as effective as OVA-CT conjugates in stimulation of the intestinal immune response, we conclu ded that the ability of the OVA conjugates to bind to the intestinal m ucosa is a prerequisite in inducing the stimulative effect. These obse rvations further demonstrate that conjugation of a protein antigen to an appropriate carrier can convert the nature of the immunization from suppressive into stimulative.