Abstract

The lab was closed in 2010. For the passed year, we have finished the following research project and have sent manuscripts for publication. There is no licensed vaccine available against Moraxella catarrhalis, an exclusive human pathogen responsible for otitis media in children and respiratory infections in adults. We previously developed vaccines based on lipooligosaccharides (LOSs) of M. catarrhalis serotypes A, B and C, each of which was shown to cover a portion of clinical strains. To generate conservative LOS antigens and eliminate a potential autoimmune response to a similar epitope between M. catarrhalis LOS moiety Gal1-4Gal1-4Glc and human Pk antigen, two LOS mutants were constructed. Mutant O35Elgt5 or O35EgalE revealed a deletion of one or two terminal galactose residues of its LOS. Each LOS molecule was purified, characterized, detoxified, and coupled to tetanus toxoid (TT) or bovine serum albumin (BSA) to form conjugates, dLOS-TT and dLOS-BSA. Subcutaneous immunizations using dLOS-TT from either mutant elicited a significant rise of serum anti-LOS immunoglobulin (Ig) G with elevated complement-mediated bactericidal activities against the wild type homologous strain O35E in rabbits. The rabbit serum elicited by the O35Elgt5 dLOS-TT also showed bactericidal activities against heterologous strains studied. In addition, the rabbit serum showed cross-reactivity among three serotype strains and clinical isolates in a whole-cell enzyme-linked immunosorbent assay (ELISA), which was further confirmed under transmission electron microscopy. In conclusion, the O35Elgt5 dLOS-TT may act as a single vaccine against most M. catarrhalis strains and therefore can be used as a vaccine component for further in vivo efficacy studies.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIADC000019-17
Application #
8148592
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
17
Fiscal Year
2010
Total Cost
$480,341
Indirect Cost

  Institution

Name
National Institute on Deafness and Other Communication Disorders
Department
Type
DUNS #
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State
Country
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