Specificity of human bactericidal antibodies against PorA P1.7,16 induced with a hexavalent meningococcal outer membrane vesicle vaccine
Autor: | Betsy Kuipers, E R van der Voort, O Tunnela, H. H. van Dijken, J T Poolman, Stephen L. George, J van der Biezen, P van der Ley |
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Rok vydání: | 1996 |
Předmět: |
Adult
Blood Bactericidal Activity Molecular Sequence Data Restriction Mapping Immunology Dose-Response Relationship Immunologic Porins Cross Reactions Meningitis Meningococcal Neisseria meningitidis Biology medicine.disease_cause Microbiology Epitope Epitopes Transformation Genetic Antibody Specificity Escherichia coli medicine Humans Point Mutation Amino Acid Sequence DNA Primers Vaccines Synthetic Base Sequence Point mutation Immunogenicity biology.organism_classification Antibodies Bacterial Infectious Diseases Bacterial Vaccines biology.protein Immunization Parasitology Neisseriaceae Antibody Bacterial outer membrane Bacterial Outer Membrane Proteins Plasmids Research Article |
Zdroj: | Infection and Immunity. 64:2745-2751 |
ISSN: | 1098-5522 0019-9567 |
Popis: | A set of isogenic strains was constructed from the meningococcal reference strain H44/76 (B:15:P1.7,16) which differed only in their outer membrane protein (OMP) compositions. First, three isogenic strains lacking the expression of either class 3 (PorB) or class 4 (RmpM) OMP or both were obtained. Second, three isogenic class 1 OMP loop-deficient strains of H44/76 lacking the predicted loop 1 or 4 or both of class 1 OMP (PorA) were obtained. Third, three isogenic class 1 OMP strains which differed by point mutations in the predicted loop 4 of subtype P1.16 were constructed. Strains were constructed through transformation with gene constructs made in Escherichia coli and their homologous recombination into the meningococcal chromosome. This study describes the contribution of one of the six class 1 OMPs, PorA P1.7,16, in the development of bactericidal antibodies after a single immunization of adult volunteers with 50 or 100 micrograms of protein within a hexavalent PorA outer membrane vesicle vaccine. PorA-, PorB-, and RpmM-deficient isogenic strains were used to define the human immune response against PorA. The loop-deficient isogenic strains were used to define the contribution of loops 1 and 4 of PorA in the development of bactericidal anti-PorA antibodies. The isogenic strains carrying a point mutation in loop 4 were used to study the cross-reactivity of the induced bactericidal antibodies against target strains showing microheterogeneity. The results indicate that a single immunization with the hexavalent PorA vaccine induced a dose-dependent bactericidal immune response, which is directed mainly against PorA. The epitope specificity of antibodies is directed mostly against loop 1, although loop 4 and as-yet-unidentified epitopes of PorA P1.7,16 are also involved. |
Databáze: | OpenAIRE |
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