Skip to main content
PMC home page
Infection and Immunity logoLink to Infection and Immunity
. 1995 Sep;63(9):3473–3478. doi: 10.1128/iai.63.9.3473-3478.1995

Conjugates of synthetic cyclic peptides elicit bactericidal antibodies against a conformational epitope on a class 1 outer membrane protein of Neisseria meningitidis.

P Hoogerhout 1, E M Donders 1, J A van Gaans-van den Brink 1, B Kuipers 1, H F Brugghe 1, L M van Unen 1, H A Timmermans 1, G J ten Hove 1, A P de Jong 1, C C Peeters 1, et al.
PMCID: PMC173479  PMID: 7543883

Abstract

Bactericidal antibodies directed against surface loops of class 1 outer membrane proteins play a crucial role in protection against meningitis and sepsis caused by Neisseria meningitidis. So far, all efforts to obtain protective antibodies against these apparently conformational epitopes by using linear peptide analogs have been in vain. In this study, conjugates of head-to-tail cyclic peptides encompassing the predicted top of a protective surface loop were used for immunization. A series of 18 cyclic peptides with a ring size ranging from 7 to 17 residues, conjugated to tetanus toxoid, was investigated. Antipeptide and anti-whole-cell immunoglobulin G (IgG) titers elicited by the conjugates were determined. Conjugates of three peptides, containing 14, 15, and 17 amino acid residues (peptides 7, 12, and 13, respectively), induced an anti-whole-cell titer when Quillaja saponin A was used as the adjuvant. When alum was used as the adjuvant, the conjugate of peptide 12 did not elicit an anti-whole-cell response. From the Quillaja saponin A group, some of the sera obtained with conjugates of peptides 7 and 12 and all sera obtained with the peptide 13 conjugate were bactericidal in vitro. None of the sera evoked with alum as the adjuvant showed bactericidal activity. Nonbactericidal sera contained IgG1 primarily, whereas bactericidal sera showed significant titers of IgG2a and IgG2b. Class 1 protein-derived synthetic cyclic peptides which are capable of eliciting bactericidal antibodies, such as peptide 13 derived from meningococcal strain H44/76, represent potential candidates for a (semi)synthetic vaccine against meningococcal disease.

Full Text

The Full Text of this article is available as a PDF (245.4 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abdillahi H., Poolman J. T. Neisseria meningitidis group B serosubtyping using monoclonal antibodies in whole-cell ELISA. Microb Pathog. 1988 Jan;4(1):27–32. doi: 10.1016/0882-4010(88)90045-9. [DOI] [PubMed] [Google Scholar]
  2. Arnon R., Maron E., Sela M., Anfinsen C. B. Antibodies reactive with native lysozyme elicited by a completely synthetic antigen. Proc Natl Acad Sci U S A. 1971 Jul;68(7):1450–1455. doi: 10.1073/pnas.68.7.1450. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Barlos K., Gatos D., Kutsogianni S., Papaphotiou G., Poulos C., Tsegenidis T. Solid phase synthesis of partially protected and free peptides containing disulphide bonds by simultaneous cysteine oxidation-release from 2-chlorotrityl resin. Int J Pept Protein Res. 1991 Dec;38(6):562–568. doi: 10.1111/j.1399-3011.1991.tb01540.x. [DOI] [PubMed] [Google Scholar]
  4. Bjune G., Høiby E. A., Grønnesby J. K., Arnesen O., Fredriksen J. H., Halstensen A., Holten E., Lindbak A. K., Nøkleby H., Rosenqvist E. Effect of outer membrane vesicle vaccine against group B meningococcal disease in Norway. Lancet. 1991 Nov 2;338(8775):1093–1096. doi: 10.1016/0140-6736(91)91961-s. [DOI] [PubMed] [Google Scholar]
  5. Brugghe H. F., Timmermans H. A., Van Unen L. M., Ten Hove G. J., Van de Werken G., Poolman J. T., Hoogerhout P. Simultaneous multiple synthesis and selective conjugation of cyclized peptides derived from a surface loop of a meningococcal class 1 outer membrane protein. Int J Pept Protein Res. 1994 Feb;43(2):166–172. doi: 10.1111/j.1399-3011.1994.tb00518.x. [DOI] [PubMed] [Google Scholar]
  6. Christodoulides M., McGuinness B. T., Heckels J. E. Immunization with synthetic peptides containing epitopes of the class 1 outer-membrane protein of Neisseria meningitidis: production of bactericidal antibodies on immunization with a cyclic peptide. J Gen Microbiol. 1993 Aug;139(8):1729–1738. doi: 10.1099/00221287-139-8-1729. [DOI] [PubMed] [Google Scholar]
  7. Høiby E. A., Rosenqvist E., Frøholm L. O., Bjune G., Feiring B., Nøkleby H., Rønnild E. Bactericidal antibodies after vaccination with the Norwegian meningococcal serogroup B outer membrane vesicle vaccine: a brief survey. NIPH Ann. 1991 Dec;14(2):147–156. [PubMed] [Google Scholar]
  8. McGuinness B., Barlow A. K., Clarke I. N., Farley J. E., Anilionis A., Poolman J. T., Heckels J. E. Deduced amino acid sequences of class 1 protein (PorA) from three strains of Neisseria meningitidis. Synthetic peptides define the epitopes responsible for serosubtype specificity. J Exp Med. 1990 Jun 1;171(6):1871–1882. doi: 10.1084/jem.171.6.1871. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Muller S., Plaué S., Samama J. P., Valette M., Briand J. P., Van Regenmortel M. H. Antigenic properties and protective capacity of a cyclic peptide corresponding to site A of influenza virus haemagglutinin. Vaccine. 1990 Aug;8(4):308–314. doi: 10.1016/0264-410x(90)90086-2. [DOI] [PubMed] [Google Scholar]
  10. Saukkonen K., Leinonen M., Abdillahi H., Poolman J. T. Comparative evaluation of potential components for group B meningococcal vaccine by passive protection in the infant rat and in vitro bactericidal assay. Vaccine. 1989 Aug;7(4):325–328. doi: 10.1016/0264-410x(89)90194-1. [DOI] [PubMed] [Google Scholar]
  11. Tommassen J., Vermeij P., Struyvé M., Benz R., Poolman J. T. Isolation of Neisseria meningitidis mutants deficient in class 1 (porA) and class 3 (porB) outer membrane proteins. Infect Immun. 1990 May;58(5):1355–1359. doi: 10.1128/iai.58.5.1355-1359.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Wedege E., Frøholm L. O. Human antibody response to a group B serotype 2a meningococcal vaccine determined by immunoblotting. Infect Immun. 1986 Feb;51(2):571–578. doi: 10.1128/iai.51.2.571-578.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Wedege E., Michaelsen T. E. Human immunoglobulin G subclass immune response to outer membrane antigens in meningococcal group B vaccine. J Clin Microbiol. 1987 Aug;25(8):1349–1353. doi: 10.1128/jcm.25.8.1349-1353.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Wiertz E. J., van Gaans-van den Brink J. A., Gausepohl H., Prochnicka-Chalufour A., Hoogerhout P., Poolman J. T. Identification of T cell epitopes occurring in a meningococcal class 1 outer membrane protein using overlapping peptides assembled with simultaneous multiple peptide synthesis. J Exp Med. 1992 Jul 1;176(1):79–88. doi: 10.1084/jem.176.1.79. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Zollinger W. D., Boslego J., Moran E., Garcia J., Cruz C., Ruiz S., Brandt B., Martinez M., Arthur J., Underwood P. Meningococcal serogroup B vaccine protection trial and follow-up studies in Chile. The Chilean National Committee for Meningococcal Disease. NIPH Ann. 1991 Dec;14(2):211–213. [PubMed] [Google Scholar]
  16. de Moraes J. C., Perkins B. A., Camargo M. C., Hidalgo N. T., Barbosa H. A., Sacchi C. T., Landgraf I. M., Gattas V. L., Vasconcelos H. de G., Gral I. M. Protective efficacy of a serogroup B meningococcal vaccine in Sao Paulo, Brazil. Lancet. 1992 Oct 31;340(8827):1074–1078. doi: 10.1016/0140-6736(92)93086-3. [DOI] [PubMed] [Google Scholar]
  17. van der Ley P., Heckels J. E., Virji M., Hoogerhout P., Poolman J. T. Topology of outer membrane porins in pathogenic Neisseria spp. Infect Immun. 1991 Sep;59(9):2963–2971. doi: 10.1128/iai.59.9.2963-2971.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES