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1.
Vaccine ; 28(31): 5057-67, 2010 Jul 12.
Article in English | MEDLINE | ID: mdl-20653107

ABSTRACT

A vaccine based on native outer membrane vesicles (NOMV) that has potential to provide safe, broad based protection against group B strains of Neisseria meningitidis has been developed. Three antigenically diverse group B strains of N. meningitidis were chosen and genetically modified to improve safety and expression of desirable antigens. Safety was enhanced by disabling three genes: synX, lpxL1, and lgtA. The vaccine strains were genetically configured to have three sets of antigens each with potential to induce protective antibodies against a wide range of group B strains. Preliminary immunogenicity studies with combined NOMV from the three strains confirmed the capacity of the vaccine to induce a broad based bactericidal antibody response. Analysis of the bactericidal activity indicated that antibodies to the LOS were responsible for a major portion of the bactericidal activity and that these antibodies may enhance the bactericidal activity of anti-protein antibodies.


Subject(s)
Antigens, Bacterial/immunology , Bacterial Outer Membrane Proteins/immunology , Meningococcal Vaccines/immunology , Neisseria meningitidis, Serogroup B/genetics , Animals , Antibodies, Bacterial/blood , Antibody Formation , Gene Knockout Techniques , Mice , Neisseria meningitidis, Serogroup B/immunology
2.
Environ Microbiol ; 6(2): 145-58, 2004 Feb.
Article in English | MEDLINE | ID: mdl-14756879

ABSTRACT

Photobacterium leiognathi forms a bioluminescent symbiosis with leiognathid fishes, colonizing the internal light organ of the fish and providing its host with light used in bioluminescence displays. Strains symbiotic with different species of the fish exhibit substantial phenotypic differences in symbiosis and in culture, including differences in 2-D PAGE protein patterns and profiles of indigenous plasmids. To determine if such differences might reflect a genetically based symbiont-strain/host-species specificity, we profiled the genomes of P. leiognathi strains from leiognathid fishes using PFGE. Individual strains from 10 species of leiognathid fishes exhibited substantial genomic polymorphism, with no obvious similarity among strains; these strains were nonetheless identified as P. leiognathi by 16S rDNA sequence analysis. Profiling of multiple strains from individual host specimens revealed an oligoclonal structure to the symbiont populations; typically one or two genomotypes dominated each population. However, analysis of multiple strains from multiple specimens of the same host species, to determine if the same strain types consistently colonize a host species, demonstrated substantial heterogeneity, with the same genomotype only rarely observed among the symbiont populations of different specimens of the same host species. Colonization of the leiognathid light organ to initiate the symbiosis therefore is likely to be oliogoclonal, and specificity of the P. leiognathi/leiognathid fish symbiosis apparently is maintained at the bacterial species level rather than at the level of individual, genomotypically defined strain types.


Subject(s)
Fishes/microbiology , Photobacterium/genetics , Polymorphism, Genetic , Symbiosis/physiology , Animals , DNA, Bacterial/analysis , Genome , Photobacterium/classification , Photobacterium/physiology , Phylogeny , Plasmids/genetics , Plasmids/metabolism , Proteome
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