Lactoferrin inhibits immunostimulatory activity of CpG ODN after mucosal or parenteral delivery

Synthetic oligodeoxynucleotides containing immunostimulatory CpG motifs (CpG ODN) are potent Th1-biased adjuvants with mucosal or parenteral delivery. Lactoferrin (U), which is normally present at mucosal surfaces and sites of acute bacterial infection, has been shown to inhibit the immunostimulatory effects of CpG ODN in vitro. Herein we investigated whether this also occurred in vivo. BALB/c mice were immunized with hepatitis B surface antigen (HBsAg) alone, or in combination with CpG ODN and/or Lf by oral, intranasal (IN) or intramuscular (IM) routes, and Ag-specific humoral and cell-mediated immune responses were subsequently measured. When co-administered with HBsAg alone, Lf did not affect Ag-specific immunity. However, when co-administered with HBsAg + CpG ODN, Lf inhibited CpG-augmented effects (e.g., CTL with IN, oral, IM; antibodies with IN). These findings support the hypothesis that Lf may down-regulate the pro-inflammatory responses to CpG-containing bacterial DNA and synthetic oligodeoxynucleotides.