Inhibition of Specific Immune Responses by Feeding Protein Antigens II. Effects of Prior Passive and Active Immunization

Feeding of 20 mg of ovalbumin (OVA) to normal, high-responder BDF1 mice produced virtually complete unresponsiveness to subsequent parenteral immunization with OVA in A1(OH) 3 adjuvant. In previously immunized animals, a single intragastric feeding of 1 to 20 mg of OVA resulted in secondary antibody responses. Primary antigen-binding titers (Farr assay) showed graded increases that were directly proportional to oral dose of antigen. The time course of responses was parallel to responses in mice boosted i.p. with soluble antigen. IgE antibody titers also increased significantly in response to feeding of OVA, but were not dose dependent in the range tested. Despite effective boosting of ongoing antibody responses by feeding, subsequent responsiveness to parenteral immunization with OVA in adjuvant was significantly reduced in mice fed larger doses of antigen. In normal mice, when feeding was preceded on the same day by parenteral injection of 20 µg of purified anti-OVA antibodies, the degree of tolerance associated with feeding was substantially reduced, suggesting that specific antibodies may contribute importantly to differences between normal and immune mice in response to feeding. In addition, subcutaneous priming with 10 µg of soluble OVA at the time of feeding produced an intermediate level of responsiveness to later immunization in relation to an exposure to OVA by either route alone. The pattern of results suggests that antigen-derived material absorbed from gut has a dual immunogenic and tolerogenic potential, such that the net effect of feeding can be strongly influenced by responses to past and concurrent contacts with specific antigen.