title: Conjugates of synthetic cyclic peptides elicit bactericidal antibodies against a conformational epitope on a class 1 outer membrane protein of Neisseria meningitidis.
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.
authors.affiliation: Laboratory of Vaccine Development and Immune Mechanisms, National Institute of Public Health and Environmental Protection, Bilthoven, The Netherlands.
authors.forename: P
authors.initials: P
authors.lastname: Hoogerhout
authors.forename: E M
authors.initials: EM
authors.lastname: Donders
authors.forename: J A
authors.initials: JA
authors.lastname: van Gaans-van den Brink
authors.forename: B
authors.initials: B
authors.lastname: Kuipers
authors.forename: H F
authors.initials: HF
authors.lastname: Brugghe
authors.forename: L M
authors.initials: LM
authors.lastname: van Unen
authors.forename: H A
authors.initials: HA
authors.lastname: Timmermans
authors.forename: G J
authors.initials: GJ
authors.lastname: ten Hove
authors.forename: A P
authors.initials: AP
authors.lastname: de Jong
authors.forename: C C
authors.initials: CC
authors.lastname: Peeters
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis*; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009345:Neisseria meningitidis / Q000276:immunology*; D010456:Peptides, Cyclic / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D001425:Bacterial Outer Membrane Proteins; D000939:Epitopes; D010456:Peptides, Cyclic