Serogroup-specific nucleotide sequences in the molecular typing of bacterial isolates and the preparation of vaccines thereto

摘要

The present invention is based on the discovery of meningococcal isolates having genetic markers of a particular serogroup but expressing a capsular polysaccharide of a different serogroup. These isolates and prototype serogroup A, B, C, Y and W-135 strains were used to define the capsular biosynthetic operon of the major meningococcal serogroups and to show that capsule switching occurs as a result of allelic exchange of, for example, the polysialyl-transferase gene. Findings of capsule switching in vivo indicate that closely related virulent meningococcal clones may not be recognized by traditional serogroup-based surveillance and can escape vaccine-induced or natural protective immunity by capsule switching. The invention provides recombinant meningococcal strains, recombinant DNA constructs and immunological preparations useful as diagnostic probes for detection and diagnosis of meningococcal diseases, screening for specific meningococcal serogroups and broad based immunizations with multivalent capsular polysaccharide conjugate vaccines.