Lactoferrin as an Adjuvant for the Generation of Delayed Type Hypersensitivity to Orally Administered Antigen.

OBJECTIVE: The aim of this investigation was to evaluate the property of bovine lactoferrin (LF) in the generation of delayed type hypersensitivity (DTH) as an oral adjuvant during immunization with ovalbumin (OVA) and BCG. METHODS: LF admixed with OVA or BCG was used for immunization of CBA or C57BL/6 mice when given via oral or subcutaneous routes. Elicited DTH response was measured post immunization. Inhibition studies using mannose or galactose were accomplished by gavage prior to oral administration of antigens. LF was also examined for effects on BCG uptake by bone marrow derived macrophages (BMM). RESULTS: LF at doses of 1.0 mg and 10.0 mg, admixed with OVA (10.0 mg), significantly enhanced the antigen-specific DTH reaction. The stimulatory effects of LF were inhibited by the oral pretreatment of mice with 50.0 mg of mannose but not galactose. LF also enhanced the DTH reaction to orally administered BCG. LF enhanced uptake of BCG by BMM in a dose-dependent manner. CONCLUSION: LF was able to augment development of DTH when orally administered with OVA or BCG antigens. Inhibition studies suggest the involvement of the receptor with an affinity to mannose in mediation of the adjuvant effect. LF augmentation of the DTH response was partially effective when given in advance of oral delivery of the antigen; this effect could also be saturated by mannose. BCG studies provide preliminary evidence for LF in the potential augmentation of oral vaccination to prevent mycobacterial infection. In vitro experiments provide evidence that LF plays a role in modulation of antigen presenting cell activation.