Immunological Implications of the use of Plant Lectins for Drug and Vaccine Targeting to the Gastrointestinal Tract

Abstract

Plant lectins are under consideration as targeting agents to enhance the efficacy of orally administered drugs and vaccines. A significant issue that must be considered is the immunogenicity of these molecules since an immune response to the targeting agent may interfere with its ability to interact with the epithelium. In contrast, the ability of certain lectins to activate the immune system may be exploited in the delivery of vaccines. We previously demonstrated that plant lectins vary widely in their immunogenicity and in particular that mistletoe lectins (ML) I, II and II (MLI, MLII, MLIII) are potent immunogens when administered nasotracheally. Here, we measured immune responses following oral delivery of the MLs and assessed their ability to enhance responses to a co-administered antigen to determine if the molecules possess adjuvant activity. Oral administration of the lectins induced potent lectin-specific systemic and mucosal antibody responses. In addition, each of the three lectins possessed adjuvant activity when delivered orally together with ovalbumin (OVA). The lectins enhanced both serum and mucosal antibody responses to the co-delivered antigen. This shows for the first time that MLI, MLII and MLIII possess adjuvant activity when administered orally and may provide a platform for the generation of effective mucosal adjuvants.

Keywords::

• Adjuvant
• Drug delivery
• Mistletoe lectin
• Plant lectin
• Targeting
• Type 2 RIP
• CT, cholera toxin
• LEA, Lycopersicum esculentum agglutinin 1
• LTB, Escherichia coli heat-labile enterotoxin B subunit
• MLI, Mistletoe lectin I
• MLII, Mistletoe lectin II
• MLIII, Mistletoe lectin III
• PHA, Phaseolus vulgaris agglutinin
• STL, Solonasum tuberosum lectin
• UEA-1, Ulex europaeus agglutinin 1
• WGA, Triticum vulgaris agglutinin