Abstract

Nontypeable Haemophilus influenzae (NTHi) is a major pathogen causing otitis media in children. Lipooligosaccharide (LOS), one of the most important surface antigens in NTHi, is immunogenic and a potential target of bactericidal antibodies during Haemophilus otitis media. We have prepared detoxified LOS-protein conjugates as a possible vaccine candidate to induce a long-term immune response for the prevention of NTHi otitis media in young children. In order to characterize biologically important epitopes of NTHi, twenty- one mouse MAbs against strain 9274 were prepared. The isotypes, the specificity and the functions of these MAbs were characterized. The results showed that two of these MAbs are IgG3 and the others are IgM. Two of these MAbs are against outer membrane proteins and the others are against LOS. Interestingly, ten of the MAbs showed bactericidal activities and some of them showed opsonophagocytic killing with human polymorphonuclear leukocytes. These results indicate NTHi LOS contains protective epitopes which can be used as a vaccine component. Further investigation will be needed to identify these functional epitopes.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Intramural Research (Z01)
Project #
1Z01DC000019-95
Application #
5201735
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
95
Fiscal Year
1995
Total Cost
Indirect Cost

  Institution

Name
National Institute on Deafness and Other Communication Disorders
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

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
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
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
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