Novel immunogenic polypeptides for the induction of protective immune response against pathogenic microorganisms and method for their production
Description of invention:
Key targets of protective immune response in bacteria are surface polysaccharides found in a number of bacteria including pneumococci, streptococci, staphylococci, meningococci, Salmonella, Shigella and Hemophilus influenza. A number of viruses, including rotaviruses, parainfluenza, influenza and immuno deficiency viruses also express polysaccharide antigens on their surface.
There are numerous drawbacks to using polysacccarides in vaccines, including difficulty and cost to synthesize or purify which comprises the risk of contaminants with endotoxic activity. Moreover, they induce predominantly T-cell independent response, without strong B cell memory response. Most vaccines therefore use peptides or peptide compounds as active components. There is a clear need to design peptides able to immunologically mimic antigenic polysaccharides and induce appropriate protective immune response.
One promising design strategy is the screening of phage-displayed random peptide libraries screened with specific antibodies targeting pathogenic microorganism surface polysaccharides. Previous approaches failed to generate any protective peptides, due to weak specificity of chosen antibodies. In the present invention, researchers at the Institut Pasteur have selected two protective monoclonal antibodies induced against Shigella flexneri for screening two phage-displayed nonapeptide libraries. Peptides were selected for high specificity and high affinity to the antibody. They were found to induce a protective immune response to the pathogen in mice, demonstrating a new strategy of selection of immunogens for the development of anti-polysaccharide vaccines.
New method for producing improved monoclonal antibodies
High level of specificity for minor, poorly immunogenic and conformational antigens expressed at the surface of naturally infected erythrocytes
Pharmaceutical compositions for notably protection against pathogenic microorganisms
Antibodies useful for diagnosing microorganism infections
The new peptides induce a stronger protective immune response to pathogenic microorganisms compared to previously developed peptides
Preparation is cheaper and less time consuming than the preparation of polysaccharide or carbohydrate antigens
Phalipon A, Folgori A, Arondel J, Sgaramella G, Fortugno P, Cortese R, Sansonetti PJ, Felici F.
Eur J Immunol 1997 Oct;27(10):2620-5
US application filed September 4, 1997
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