Research Advances in Vaccines Against Middle Ear Infection
Background: Nontypeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis are two major bacteria that cause middle ear infection (otitis media) in children. Antibiotics are usually prescribed to treat this infection, but there is a need to develop a vaccine against the microbes that are involved in otitis media. Previously, scientists identified and used a major surface component of NTHi, called lipooligosaccharide (LOS), to develop a conjugate vaccine against NTHi. LOS is also a possible virulence factor in the pathogenesis of human infections caused by M. catarrhalis, but information about the roles of the oligosaccharide chain from LOS in M. catarrhalis infection remains limited.
Advances: NIDCD intramural scientists have made advances in improving the quality of these conjugate vaccines by developing a new carrier protein purified from the outer membrane of NTHi. They are testing if the new carrier would be useful for sugar-based conjugate vaccines. Using an outer membrane protein, P6, as a new carrier for NTHi LOS conjugate vaccines, scientists determined that P6 could serve as an effective carrier for conjugate vaccines and have a potential to generate better immune responses against NTHi in animal models.
In another advance, NIDCD intramural scientists have identified a kdtA gene that appears to play a role in LOS biosynthesis in M. catarrhalis. When scientists developed a mutant strain of M. catarrhalis that lacked the specific gene, the bacteria showed reduced resistance to a series of chemical compounds and were susceptible to attack by cell in normal human serum. It also could not adhere as efficiently to human epithelial cells in the respiratory tract, and was more easily cleared from the nose, throat, and lungs of a mouse that was exposed to the mutant strain. These data suggest that the gene responsible for synthesizing LOS is important for the biological activity of the LOS and the virulent capability of the bacteria.
Implications: Learning how the kdtA gene functions in LOS biosynthesis and the bacterial virulence in M. catarrhalis or identifying a new protein carrier that can be used for production of sugar-based conjugate vaccines against NTHi are providing new insights into novel vaccines or therapeutic interventions against bacteria that cause otitis media.
Citations: Peng D, Choudhury BP, Petralia RS, Carlson RW, Gu XX, Roles of 3-deoxy-D-manno-2-octulosonic acid transferase from Moraxella catarrhalis in lipooligosaccharide biosynthesis and virulence. Infect Immun 73: 4222-4230, 2005.
Wu T, Chen J, Murphy TF, Green BA, Gu XX, Investigation of Nontypeable Haemophilus influenzae outer membrane protein P6 as a new carrier for lipooligosaccharide conjugate vaccine. Vaccine EPub, 2005.
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