The purpose of this project is to develop vaccines against otitis media caused by nontypeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis. In this fiscal year, efforts are focusing on investigating if intranasal immunization with a detoxified lipooligosaccharide (LOS)-tetanus toxoid (dLOS-TT) conjugate vaccine would generate protective immunity against NTHi in a mouse model of nasopharyngeal colonization. The results demonstrated that intranasal immunization with dLOS-TT plus adjuvant cholera toxin (CT) significantly induced LOS-specific IgA antibodies in mouse external secretions, especially in nasal wash (90-fold), bronchoalveolar lavage fluid (25-fold), saliva (13-fold) and fecal extract (3-fold). LOS-specific IgA antibody forming cells were also found in mucosal and lymphoid tissues with their highest numbers in the nasal passage (528 per 106 cells). In addition, the intranasal immunization elicited a significant rise of LOS-specific IgG (32-fold) and IgA (13-fold) in serum. For the immunized mice which had been challenged through the nose with 107 live NTHi strain 9274, the vaccine group showed a significant reduction (74%-76%) of NTHi, compared to that of control groups with CT alone or dLOS plus CT (p<0.05). Negative correlations were found between bacterial counts and the levels of nasal wash IgA or IgG, saliva IgA or serum IgG. The clearance of five heterologous strains was investigated and revealed a significant clearance in strains 3198, 5657 and 7502 but not in strains 1479 and 2019. These data suggest that intranasal immunization with dLOS-TT vaccine elicits both mucosal and systemic immunity against NTHi colonization in a mouse model of nasopharyngeal colonization. Such a vaccine and vaccination regime may be effective in humans to inhibit NTHi colonization to prevent further NTHi infections.

Project Start
Project End
Budget Start
Budget End
Support Year
8
Fiscal Year
2001
Total Cost
Indirect Cost
Name
Deafness & Other Communication Disorders
Department
Type
DUNS #
City
State
Country
United States
Zip Code
von Bartheld, Christopher S; Giannessi, Francesco (2011) The paratympanic organ: a barometer and altimeter in the middle ear of birds? J Exp Zool B Mol Dev Evol 316:402-8
Gao, Song; Peng, Daxin; Zhang, Wenhong et al. (2008) Identification of two late acyltransferase genes responsible for lipid A biosynthesis in Moraxella catarrhalis. FEBS J 275:5201-14
Yu, Shengqing; Xie, Hang; Datta, Anup et al. (2008) Galactose residues on the lipooligosaccharide of Moraxella catarrhalis 26404 form the epitope recognized by the bactericidal antiserum from conjugate vaccination. Infect Immun 76:4251-8
Peng, Daxin; Hu, Wei-Gang; Choudhury, Biswa P et al. (2007) Role of different moieties from the lipooligosaccharide molecule in biological activities of the Moraxella catarrhalis outer membrane. FEBS J 274:5350-9
Yu, Shengqing; Gu, Xin-Xing (2007) Biological and immunological characteristics of lipooligosaccharide-based conjugate vaccines for serotype C Moraxella catarrhalis. Infect Immun 75:2974-80
Zhou, Qibing; Xie, Hang; Zhang, Lin et al. (2006) cis-Terpenones as an effective chemopreventive agent against aflatoxin B1-induced cytotoxicity and TCDD-induced P450 1A/B activity in HepG2 cells. Chem Res Toxicol 19:1415-9
Hirano, Takashi; Jiao, Xinan; Chen, Zhong et al. (2006) Kinetics of mouse antibody and lymphocyte responses during intranasal vaccination with a lipooligosaccharide-based conjugate vaccine. Immunol Lett 107:131-9
Yu, Shengqing; Gu, Xin-Xing (2005) Synthesis and characterization of lipooligosaccharide-based conjugate vaccines for serotype B Moraxella catarrhalis. Infect Immun 73:2790-6
Peng, Daxin; Choudhury, Biswa P; Petralia, Ronald S et al. (2005) Roles of 3-deoxy-D-manno-2-octulosonic acid transferase from Moraxella catarrhalis in lipooligosaccharide biosynthesis and virulence. Infect Immun 73:4222-30
Hu, Wei-Gang; Berry, Julie; Chen, Jing et al. (2004) Exploration of Moraxella catarrhalis outer membrane proteins, CD and UspA, as new carriers for lipooligosaccharide-based conjugates. FEMS Immunol Med Microbiol 41:109-15

Showing the most recent 10 out of 22 publications