Skip to main content
SpringerLink
Log in

Identification of Peptides that Mimic N. meningitidis LOS Epitopes Via the Use of Combinatorial Phage-Display Libraries

  • Protocol
Meningococcal Vaccines

Part of the book series: Methods in Molecular Medicine™ ((MIMM,volume 66))

Abstract

Although capsular polysaccharide-based vaccines are effective at reducing the incidence of meningococcal disease caused by serogroups A, C, Y, and W135 (1–3), immunization against serogroup B disease using similar strategies has proven unsuccessful (4,5). The primary reason for this is that the α2,8-linked N-acetylneuraminic acid homopolymer expressed by serogroup B strains is poorly immunogenic in humans (6). Consequently, considerable effort has been devoted towards the development of alternative strategies for vaccination against serogroup B disease. Many of these newer strategies include the use of lipooligosaccharide (LOS) as a protective antigen (7). One of the approaches that we are currently pursuing involves the use of synthetic oligopeptides to stimulate antibody responses that are cross-reactive with LOS antigens expressed by serogroup B Neisseria meningitidis strains. An integral part of these studies has been the application of combinatorial phage-display technology. Described here is an overview of the methods that we have utilized to identify peptide mimics of LOS epitopes.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Twumasi, P. A., Jr., Kumah, S., Leach, A., O’Dempsey, T. J., Ceesay, S. J., Todd, J., et al. (1995) A trial of a group A plus group C meningococcal polysaccharide-protein conjugate vaccine in African infants. J. Infect. Dis. 171, 632–638.

    PubMed  Google Scholar 

  2. Anderson, E. L., Bowers, T., Mink, C. M., Kennedy, D. J., Belshe, R. B., Harakeh, H., et al. (1994) Safety and immunogenicity of meningococcal A and C polysaccharide conjugate vaccine in adults. Infect. Immun. 62, 3391–3395.

    CAS  PubMed  Google Scholar 

  3. Lieberman, J. M., Chiu, S. S., Wong, V. K., Partridge, S., Chang, S.-J., Chiu, C.-Y., et al. (1996) Safety and immunogenicity of a serogroups A/CNeisseria meningitidis oligosaccharide-protein conjugate vaccine in young children. JAMA 275, 1499–1503.

    Article  CAS  PubMed  Google Scholar 

  4. Wyle, F. A., Artenstein, M. S., Brandt, B. L., Tramont, E. C., Kasper, D. L., Altieri, P. L., et al. (1972) Immunologic response of man to group B meningococcal polysaccharide vaccines. J. Infect. Dis. 126, 514–521.

    CAS  PubMed  Google Scholar 

  5. Granoff, D. M., Bartoloni, A., Ricci, S., Gallo, E., Rosa, D., Ravenscroft, N., et al. (1998) Bactericidal monoclonal antibodies that define unique meningococcal B polysaccharide epitopes that do not cross-react with human polysialic acid. J. Immunol. 160, 5028–5036.

    CAS  PubMed  Google Scholar 

  6. Finne, J., Leinonen, M., and Makela, P. H. (1983) Antigenic similarities between brain components and bacteria causing meningitis; implications for vaccine development and pathogenesis. Lancet ii, 335–337.

    Google Scholar 

  7. Diaz Romero, J. and Outschoorn, I. M. (1994) Current status of meningococcal group B vaccine candidates: capsular or noncapsular? Clin. Microbiol. Rev. 7, 559–575.

    CAS  PubMed  Google Scholar 

  8. Schneider, H., Hale, T. L., Zollinger, W. D., Seid, R. C., Hammack, C. A., and Griffiss, J. M. (1984) Heterogeneity of molecular size and antigenic expression within lipooligosaccharides of individual strains of Neisseria gonorrhoeae and Neisseria meningitidis. Infect. Immun. 45(3), 544–549.

    CAS  PubMed  Google Scholar 

  9. Jennings, H. J., Beurret, M., Gamian, A., and Michon, F. (1987) Structure and immunochemistry of meningococcal lipopolysaccharides. Antonie van Leeuwenhoek 53, 519–522.

    Article  CAS  PubMed  Google Scholar 

  10. Jennings, H. J., Bhattacharjee, A. K., Kenne, L., Kenny, C. P., and Calver, G. (1980) The R-type lipopolysaccharides of Neisseria meningitidis. Can. J. Biochem. 58, 128–136.

    CAS  PubMed  Google Scholar 

  11. Scholten, R. J., Kuipers, B., Valkenburg, H. A., Dankert, J., Zollinger, W. D., and Poolman, J. T. (1994) Lipo-oligosaccharide immunotyping of Neisseria meningitidis by a whole-cell ELISA with monoclonal antibodies. J. Med. Microbiol. 41, 236–243.

    Article  CAS  PubMed  Google Scholar 

  12. Tsai, C. M., Mocca, L. F., and Frasch, C. E. (1987) Immunotype epitopes of Neisseria meningitidis lipooligosaccharide types 1 through 8. Infect. Immun. 55, 1652–1656.

    CAS  PubMed  Google Scholar 

  13. Tsai, C. M. and Civin, C. I. (1991) Eight lipooligosaccharides of Neisseria meningitidis react with a monoclonal antibody which binds lacto-N-neotetraose (Gal beta 1-4GlcNAc beta 1-3Gal beta 1-4Glc). Infect. Immun. 59, 3604–3609.

    CAS  PubMed  Google Scholar 

  14. Mandrell, R. E., Griffiss, J. M., and Macher, B. A. (1988) Lipooligosaccharides (LOS) of Neisseria gonorrhoeae and Neisseria meningitidis have components that are immunochemically similar to precursors of human blood group antigens. J. Exp. Med. 168, 107–126.

    Article  CAS  PubMed  Google Scholar 

  15. Kahler, C. M., Martin, L. E., Shih, G. C., Rahman, M. M., Carlson, R. W., and Stephens, D. S. (1998) The (α2–8)-linked polysialic acid capsule and lipooligosaccharide structure both contribute to the ability of serogroup B Neisseria meningitidis to resist the bactericidal activity of normal human serum. Infect. Immun. 66, 5939–5947.

    CAS  PubMed  Google Scholar 

  16. Estabrook, M. M., Griffiss, J. M., and Jarvis, G. A. (1997) Sialylation of Neisseria meningitidis lipooligosaccharide inhibits serum bactericidal activity by masking lacto-N-neotetraose. Infect. Immun. 65, 4436–4444.

    CAS  PubMed  Google Scholar 

  17. Mackinnon, F. G., Borrow, R., Gorringe, A. R., Fox, A. J., Jones, D. M., and Robinson, A. (1993) Demonstration of lipooligosaccharide immunotype and capsule as virulence factors for Neisseria meningitidis using an infant mouse intranasal infection model. Microb. Pathog. 15, 359–366.

    Article  CAS  PubMed  Google Scholar 

  18. Jones, D. M., Borrow, R., Fox, A. J., Gray, S., Cartwright, K. A., and Poolman, J. T. (1992) The lipooligosaccharide immunotype as a virulence determinant in Neisseria meningitidis. Microb. Pathog. 13, 219–224.

    Article  CAS  PubMed  Google Scholar 

  19. Dalseg, R., Wedege, E., Holst, J., Haugen, I. L., Hoiby, E. A., and Haneberg, B. (1999) Outer membrane vesicles from group B meningococci are strongly immunogenic when given intranasally to mice. Vaccine 17, 2336–2345.

    Article  CAS  PubMed  Google Scholar 

  20. Fischer, M., Carlone, G. M., Holst, J., Williams, D., Stephens, D. S., and Perkins, B. A. (1999) Neisseria meningitidis serogroup B outer membrane vesicle vaccine in adults with occupational risk for meningococcal disease. Vaccine 17, 2377–2383.

    Article  CAS  PubMed  Google Scholar 

  21. Quakyi, E. K., Frasch, C. E., Buller, N., and Tsai, C. M. (1999) Immunization with meningococcal outer-membrane protein vesicles containing lipooligosaccharide protects mice against lethal experimental group B Neisseria meningitidis infection and septic shock. J. Infect. Dis. 180, 747–754.

    Article  CAS  PubMed  Google Scholar 

  22. Verheul, A. F., Braat, A. K., Leenhouts, J. M., Hoogerhout, P., Poolman, J. T., Snippe, H., and Verhoef, J. (1991) Preparation, characterization, and immunogenicity of meningococcal immunotype L2 and L3,7,9 phosphoethanolamine group-containing oligosaccharide-protein conjugates. Infect. Immun. 59, 843–851.

    CAS  PubMed  Google Scholar 

  23. Glucksman, M. J., Bhattacharjee, S., and Makowski, L. (1992) Three-dimensional structure of a cloning vector. X-ray diffraction studies of filamentous bacteriophage M13 at 7 Å resolution. J. Mol. Biol. 226, 455–470.

    Article  CAS  PubMed  Google Scholar 

  24. Rasched, I. and Oberer, E. (1986) Ff coliphages: structural and functional relationships. Microbiol. Rev. 50, 401–427.

    CAS  PubMed  Google Scholar 

  25. Russel, M. (1991) Filamentous phage assembly. Mol. Microbiol. 5, 1607–1613.

    Article  CAS  PubMed  Google Scholar 

  26. Makowski, L. (1993) Structural constraints on the display of foreign peptides on filamentous bacteriophages. Gene 128, 5–11.

    Article  CAS  PubMed  Google Scholar 

  27. Greenwood, J., Willis, A. E., and Perham, R. N. (1991) Multiple display of foreign peptides on a filamentous bacteriophage. Peptides from Plasmodium falciparum circumsporozoite protein as antigens. J. Mol. Biol. 220, 821–827.

    Article  CAS  PubMed  Google Scholar 

  28. De Bolle, X., Laurent, T., Tibor, A., Godfroid, F., Weynants, V., Letesson, J. J., and Mertens, P. (1999) Antigenic properties of peptidic mimics for epitopes of the lipopolysaccharide from Brucella. J. Mol. Biol. 294, 181–191.

    Article  PubMed  Google Scholar 

  29. Lowman, H. B. (1997) Bacteriophage display and discovery of peptide leads for drug development. Ann. Rev. Biophys. Biomol. Struct. 26, 401–424.

    Article  CAS  Google Scholar 

  30. Lowman, H. B., Bass, S. H., Simpson, N., and Wells, J. A. (1991) Selecting high-affinity binding proteins by monovalent phage display. Biochemistry 30, 10,832–10,838.

    Article  CAS  PubMed  Google Scholar 

  31. Poolman, J. T., Kriz, Kuzemenska, P., Ashton, F., Bibb, W., Dankert, J., et al. (1995) Serotypes and subtypes of Neisseria meningitidis: results of an international study comparing sensitivities and specificities of monoclonal antibodies. Clin. Diagn. Lab. Immunol. 2, 69–72.

    CAS  PubMed  Google Scholar 

  32. Van Dam, G. J., Verheul, A. F., Zigterman, G. J., De Reuver, M. J., and Snippe, H. (1989) Estimation of the avidity of antibodies in polyclonal antisera against Streptococcus pneumoniae type 3 by inhibition ELISA. Mol. Immunol. 26, 269–274.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Bateriology, National Institute for Biological Standards and Control, Hertfordshire, UK

    Paul J. Brett & Ian M. Feavers

  2. Department of Medical Microbiology, Royal Free ⇐p; University College Medical School, London, UK

    Bambos M. Charalambous

Authors
  1. Paul J. Brett
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ian M. Feavers
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bambos M. Charalambous
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. BC Research Institute for Children’s and Women’s Health, Vancouver, BC, Canada

    Andrew J. Pollard MD, PhD

  2. Wellcome Trust Centre for the Epidemiology of Infectious Disease, Oxford, UK

    Martin C.J. Maiden PhD

Rights and permissions

Reprints and permissions

Copyright information

© 2001 Humana Press Inc., Totowa, NJ

About this protocol

Cite this protocol

Brett, P.J., Feavers, I.M., Charalambous, B.M. (2001). Identification of Peptides that Mimic N. meningitidis LOS Epitopes Via the Use of Combinatorial Phage-Display Libraries. In: Pollard, A.J., Maiden, M.C. (eds) Meningococcal Vaccines. Methods in Molecular Medicine™, vol 66. Humana Press. https://doi.org/10.1385/1-59259-148-5:181

Download citation

  • DOI: https://doi.org/10.1385/1-59259-148-5:181

  • Publisher Name: Humana Press

  • Print ISBN: 978-0-89603-801-1

  • Online ISBN: 978-1-59259-148-0

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation