title: Biological activities of antibodies elicited by lipooligosaccharide based-conjugate vaccines of nontypeable Haemophilus influenzae in an otitis media model.
abstract: Vaccination of chinchillas with nontypeable Haemophilus influenzae (NTHi) lipooligosaccharide (LOS) conjugates protected against otitis media. Correlations between the levels of conjugate-induced LOS antibodies (Abs) in sera and middle ear fluids (MEFs) and Ab-mediated biological functions and protection were examined. Following parenteral vaccination and middle ear challenge, all vaccinated animals, but none of the controls, had high titers of anti-LOS in their sera and MEFs. There was a correlation between the levels of anti-LOS IgG + M, IgG or IgA in the sera and in the MEFs (P < 0.001). An inverse correlation was found between the level of serum IgG + M and bacterial counts and between the levels of MEF Abs and bacterial counts at the early postchallenge stage (P < 0.05). Of the 39 vaccinated animals, 44% showed complete protection against otitis media, 46% (18/39) of their sera inhibited adherence of NTHi to human epithelial cells, 49% (19/39) demonstrated bactericidal activity and 49% (19/39) showed opsonophagocytic activity. In contrast, none of the controls (19) were protected, none of their sera inhibited bacterial adherence or had bactericidal activity and only 21% showed opsonophagocytosis. Our interpretation is that vaccine-induced LOS Abs transuded into the middle ear and conferred immunity to NTHi by binding to LOS of NTHi, inhibition of NTHi adherence to epithelial cells and complement-mediated bacteriolysis (or opsonophagocytosis).
authors.affiliation: Laboratory of Immunology, National Institute on Deafness and Other Communication Disorders, Rockville, MD 20850, USA.
authors.forename: J
authors.initials: J
authors.lastname: Sun
authors.forename: J
authors.initials: J
authors.lastname: Chen
authors.forename: Z
authors.initials: Z
authors.lastname: Cheng
authors.forename: J B
authors.initials: JB
authors.lastname: Robbins
authors.forename: J F
authors.initials: JF
authors.lastname: Battey
authors.forename: X X
authors.initials: XX
authors.lastname: Gu
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis* / Q000097:blood; D019138:Antibodies, Blocking / Q000097:blood; D000918:Antibody Specificity; D001770:Blood Bactericidal Activity / Q000276:immunology; D002682:Chinchilla; D015169:Colony Count, Microbial; D005122:Exudates and Transudates / Q000276:immunology / Q000382:microbiology; D018073:Haemophilus Vaccines / Q000276:immunology* / Q000627:therapeutic use; D006193:Haemophilus influenzae / Q000145:classification / Q000276:immunology*; D006801:Humans; D007106:Immune Sera / Q000032:analysis; D007132:Immunoglobulin Isotypes / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000276:immunology* / Q000627:therapeutic use; D009895:Opsonin Proteins / Q000276:immunology; D010034:Otitis Media with Effusion / Q000097:blood / Q000276:immunology* / Q000517:prevention & control; D010587:Phagocytosis / Q000276:immunology; D018074:Vaccines, Conjugate / Q000276:immunology / Q000627:therapeutic use
chemical_list: D000907:Antibodies, Bacterial; D019138:Antibodies, Blocking; D018073:Haemophilus Vaccines; D007106:Immune Sera; D007132:Immunoglobulin Isotypes; D008070:Lipopolysaccharides; D009895:Opsonin Proteins; D018074:Vaccines, Conjugate