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Anti-idiotypic monoclonal antibodies for mucoid Pseudomonas aeruginosa, their preparation and use (Text)

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  • Background of the invention: The present invention relates generally to infectious diseases and antibodies, and, more particularly, to a new hybridoma cell line for production of anti-idiotypic monoclonal antibodies directed to an opsonic monoclonal antibody specific to mucoid exopolysaccharide of Pseudomonas aeruginosa. Description of related articles: Mucoid strains of Pseudomonas aeruginosa are the primary pulmonary pathogen for cystic fibrosis (CF) patients. Acquisition of this organism in the lungs is invariably associated with clinical decline, and there is a strong association between expression of the mucoid phenotype and growth in the lungs of CF patients. Mucoid exopolysaccharide (MEP), the primary constituent of the extracellular slime coat of mucoid strains, appears to be an important antigen in the pathophysiology of P. aeruginosa infection of CF patients. MEP expression promotes adherence of mucoid P. aeruginosa to tracheal cells and to respiratory mucins and antibodies to MEP are important to host defenses against the organism. According to earlier work (see Pier, G. B., et al., N. Engl. J. Med. 1987; 317: 793-798) induction of opsonic antibodies to MEP will probably be an important property of vaccines considered as candidates for prevention of mucoid P. aeruginosa infection in CF patients. Most CF patients respond to infection with high titers of nonopsonic antibody to MEP, and these antibodies fail to prevent progression of the infection. However, a small number of older (>12 years) CF patients have opsonic antibodies to MEP, are not infected with P. aeruginosa, and have an overall better clinical status. Furthermore, opsonic antibodies protect experimental animals from chronic mucoid P. aeruginosa lung infections. Pier, G. B., et al., Science 1990; 249: 537-540, the contents of which are incorporated herein by reference. Recently, it has been observed that the heteropolymeric nature of MEP results in the presence of both common and type-specific epitopes. In addition, the common epitopes are further divided into those that bind opsonizing antibodies and those that bind nonopsonizing antibody. Most naturally occurring antibodies to MEP function poorly in in vitro opsonophagocytic assays with complement, and are unable to protect animals following intratracheal challenge with bacteria encased in agar beads. By contrast, antibodies that are highly opsonic protect animals against infection and are found among some older CF patients who are not colonized with P. aeruginosa. Opsonizing antibodies to MEP are usually not found in younger noncolonized or chronically colonized CF patients. These findings have suggested a protective effect for the opsonizing antibodies. It is believed that opsonizing antibodies to the MEP antigen will generally protect animals, including humans, livestock, and mammals generally, from infection. MEP has become a promising vaccine candidate for the prevention of infection with P. aeruginosa in CF patients.
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Date
  • 1993-08-03
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  • Delphion Inc., www.delphion.com
Language
  • English
Type
  • text
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  • text/pdf
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  • ksl:casepat-us5233024
Identifier http://hdl.handle.net/2186/ksl:casepat-us5233024
HANDLE http://hdl.handle.net/2186/ksl:casepat-us5233024
Access Rights Open Access
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