Enhancement of Nasal Clearance of Nontypeable Haemophilus influenzae by Oral Immunization with Outer Membrane Proteins

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Abstract
BALB/c mice were orally immunized with liposomes containing outer membrane proteins (OMPs) isolated from nontypeable Haemophilus influenzae (NTHi) and GM-53 as an adjuvant daily for 14 days. Anti-OMP IgA antibody titers in nasal wash, saliva, and fecal extract were significantly increased after the immunization. Although anti-OMP IgM and IgG antibodies were detected in serum, serum IgA antibodies specific to OMPs were not found. Enzyme-linked immunospot assay showed an increased number of OMP-specific IgA-secreting cells in nasal passages, intestinal lamina propria lymphocytes, and the spleen. Following oral immunization, a suspension of live NTHi was injected into the nose; nasal washes were collected 12 h after the inoculation. The number of NTHi in nasal washes was significantly reduced in mice immunized with liposomes containing OMPs and GM-53 compared to that in mice immunized with liposomes containing GM-53 alone. There was a significant negative correlation between the number of NTHi and anti-OMP IgA antibody titers in nasal washes. These findings suggest that antigen-specific IgA responses in the nose can be induced by oral immunization with OMPs and might be associated with the ability to clear NTHi from the nose.