Otitis media leads to enormous morbidity and to direct annual healthcare costs estimated to be $3 billion in the U.S. Chronic obstructive pulmonary disease (COPD) is the fourth most common cause of death in the U.S. Bacterial infection in COPD causes substantial morbidity and mortality. Two of the three most common bacterial pathogens to cause otitis media and respiratory tract infections in COPD are non-typeable Haemophilus influenzae (NTHI) and Moraxella catarrhalis. The development of vaccines to prevent otitis media and respiratory tract infections in adults with COPD would have important impact in reducing mortality, preventing morbidity and reducing healthcare costs in these settings. This program project proposes studies which will elucidate the immune response to specific antigens of NTHI and M. catarrhalis. Our hypothesis is that the pattern of respiratory tract infections due to NTHI and M. catarrhalis in children and adults depends on the immune response to specific surface antigens of the organisms.
The aims of the project will be accomplished through the efforts of a multi-disciplinary research team which will collaborate to carry out three interrelated projects. Project 1 will characterized the role of human T cell responses to protein P6, a promising vaccine antigen will be determined through studies with carefully defined samples from humans. Project 3 will focus on antigenic characterization of the lipooligosaccharide (LOS) of M. catarrhalis, the role of NOS as an adhesin and the human immune response to determinants on the LOS molecule. An Administrative/Statistical Core will coordinate the program and provide statistical expertise to each of the projects. Since NTHI and M. catarrhalis are exclusively human pathogens, a strong emphasis is placed on elucidation of the human immune response. The proposed studies will advance the field of vaccine development to prevent otitis media and respiratory tract infections in COPD.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
5P01AI046422-04
Application #
6757242
Study Section
Microbiology and Infectious Diseases B Subcommittee (MID)
Program Officer
Klein, David L
Project Start
2001-08-15
Project End
2006-06-30
Budget Start
2004-07-01
Budget End
2006-06-30
Support Year
4
Fiscal Year
2004
Total Cost
$615,821
Indirect Cost
Name
State University of New York at Buffalo
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
038633251
City
Buffalo
State
NY
Country
United States
Zip Code
14260
Luke-Marshall, Nicole R; Edwards, Katie J; Sauberan, Shauna et al. (2013) Characterization of a trifunctional glucosyltransferase essential for Moraxella catarrhalis lipooligosaccharide assembly. Glycobiology 23:1013-21
Schwingel, Johanna M; Edwards, Katie J; Cox, Andrew D et al. (2009) Use of Moraxella catarrhalis lipooligosaccharide mutants to identify specific oligosaccharide epitopes recognized by human serum antibodies. Infect Immun 77:4548-58
Schwingel, Johanna M; St Michael, Frank; Cox, Andrew D et al. (2008) A unique glycosyltransferase involved in the initial assembly of Moraxella catarrhalis lipooligosaccharides. Glycobiology 18:447-55
Adlowitz, Diana G; Kirkham, Charmaine; Sethi, Sanjay et al. (2006) Human serum and mucosal antibody responses to outer membrane protein G1b of Moraxella catarrhalis in chronic obstructive pulmonary disease. FEMS Immunol Med Microbiol 46:139-46
Murphy, Timothy F; Brauer, Aimee L; Grant, Brydon J B et al. (2005) Moraxella catarrhalis in chronic obstructive pulmonary disease: burden of disease and immune response. Am J Respir Crit Care Med 172:195-9
Edwards, Katie J; Schwingel, Johanna M; Datta, Anup K et al. (2005) Multiplex PCR assay that identifies the major lipooligosaccharide serotype expressed by Moraxella catarrhalis clinical isolates. J Clin Microbiol 43:6139-43
Adlowitz, Diana G; Sethi, Sanjay; Cullen, Paul et al. (2005) Human antibody response to outer membrane protein G1a, a lipoprotein of Moraxella catarrhalis. Infect Immun 73:6601-7
McMahon, Michelle; Murphy, Timothy F; Kyd, Jennelle et al. (2005) Role of an immunodominant T cell epitope of the P6 protein of nontypeable Haemophilus influenzae in murine protective immunity. Vaccine 23:3590-6
Murphy, Timothy F; Brauer, Aimee L; Aebi, Christoph et al. (2005) Antigenic specificity of the mucosal antibody response to Moraxella catarrhalis in chronic obstructive pulmonary disease. Infect Immun 73:8161-6
Edwards, Katie J; Allen, Simon; Gibson, Bradford W et al. (2005) Characterization of a cluster of three glycosyltransferase enzymes essential for Moraxella catarrhalis lipooligosaccharide assembly. J Bacteriol 187:2939-47

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