Outer membrane proteins as a carrier for detoxified lipooligosaccharide conjugate vaccines for nontypeable Haemophilus influenzae.
Nontypeable Haemophilus influenzae (NTHi) is a common cause of otitis media and respiratory tract infections. Outer membrane proteins (OMP) and lipooligosaccharide (LOS) are major surface antigens of NTHi and potential vaccine candidates. De-O-acylated LOS (dLOS) or oligosaccharide (OS) was coupled to total OMP to form dLOS-OMP and OS-OMP conjugates, while a dLOS-tetanus toxoid (TT) was synthesized for comparison. These conjugates were evaluated in mice and rabbits for immunogenicity. dLOS-OMP elicited a better boostable antibody response against LOS than did dLOS-TT, while OS-OMP was not immunogenic. Formulation of the conjugates with Ribi adjuvant significantly enhanced the immunogenicity of dLOS-OMP and dLOS-TT but not that of OS-OMP. In addition, rabbit antisera elicited by dLOS-OMP but not dLOS-TT (or OMP alone) demonstrated bactericidal activity against 40% of the NTHi strains tested. These results indicate that dLOS is a better derivative of LOS than OS and that OMP is a good carrier for NTHi LOS-based conjugate vaccines.
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Laboratory of Immunology, National Institute on Deafness and Other Communication Disorders, Rockville, Maryland 20850, USA.
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D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D001770:Blood Bactericidal Activity; D005260:Female; D018073:Haemophilus Vaccines / Q000276:immunology*; D007106:Immune Sera / Q000276:immunology; D007114:Immunization; D008070:Lipopolysaccharides / Q000276:immunology*; D051379:Mice; D011817:Rabbits; D018074:Vaccines, Conjugate / Q000276:immunology
D000907:Antibodies, Bacterial; D001425:Bacterial Outer Membrane Proteins; D018073:Haemophilus Vaccines; D007106:Immune Sera; D008070:Lipopolysaccharides; D018074:Vaccines, Conjugate; C023023:lipid-linked oligosaccharides