Epitope specificity of murine and human bactericidal antibodies against PorA P1.7,16 induced with experimental meningococcal group B vaccines |
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Authors: | Eileene M. Rouppe van der Voort Betsy Kuipers Humphrey F. Brugghe Leontine M.A. van Unen Hans A.M. Timmermans Peter Hoogerhout Jan T. Poolman |
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Affiliation: | Laboratory of Vaccine Development and Immune Mechanisms, National Institute of Public Health and the Environment, Laboratory of Vaccine Development and Immune Mechanisms (LVM), P.O. Box 1, 3720 BA Bilthoven, The Netherlands;Institute for Research in Extramural Medicine, Vrije Universiteit, Amsterdam, The Netherlands |
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Abstract: | Synthetic peptides derived from the predicted loops 1 and 4 of meningococcal PorA, sero-subtype P1.7,16, were used to study the epitope specificity of murine and human PorA P1.7,16 bactericidal antibodies. The predicted loops 1 and 4 are surface exposed and carry in their apices the sero-subtype epitopes P1.7 (loop 1) or P1.16 (loop 4), respectively. Peptides were synthesized as mono- and multimeric peptides. Murine monoclonal and polyclonal antibodies were induced with meningococcal whole cell preparations. Polyclonal antibodies were evoked in volunteers after one immunization with 50 μg or 100 μg protein of a hexavalent meningococcal PorA vesicle vaccine. The induction of PorA antibodies was determined in ELISA using purified PorA P1.7,16. The epitope specificity of anti-PorA antibodies for both murine and human antibodies could be demonstrated by direct peptide ELISA using overlapping multimeric peptides almost spanning the entire loops 1 or 4 of the protein. The capacity of peptides to inhibit the bactericidal activity of murine and human antibodies was investigated using meningococcal strain H44/76 (B:15:P1.7,16) as a target strain. Bactericidal activities could be inhibited with both monomeric and multimeric peptides derived from epitopes P1.7 and P1.16. |
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Keywords: | Synthetic peptide PorA P1.7,16 Loop-specific antibody Meningococcal vaccine |
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