ANTIGENIC DIVERSITY OF MENINGOCOCCAL OUTER-MEMBRANE PROTEIN PORA HAS IMPLICATIONS FOR EPIDEMIOLOGIC ANALYSIS AND VACCINE DESIGN

The currently used serological subtyping scheme for the pathogen Neiss eria meningitidis is not comprehensive, a proportion of isolates are r eported as not subtypeable (NST), and few isolates are fully character ized with two subtypes for each strain. To establish the reasons for t his and to assess the effectiveness of DNA-based subtyping schemes, do t blot hybridization and nucleotide sequence analyses were used to cha racterize the genes encoding antigenic variants of the meningococcal s ubtyping antigen, the PorA protein. pi total of 233 strains, including 174 serologically NST and 59 partially or completely subtyped meningo coccal strains, were surveyed. The NST isolates were chosen to be temp orally and geographically representative of NST strains, isolated in E ngland and Wales, and submitted to the Meningococcal Reference Unit in the period 1989 to 1991. The DNA-based analyses demonstrated that all of the strains examined possessed a porA gene. Some of these strains were serologically NST because of a lack of monoclonal antibodies agai nst certain PorA epitopes; in other cases, strains expressed minor var iants of known PorA epitopes that did not react with monoclonal antibo dies in serological assays. Lack of expression remained a possible exp lanation for serological typing failure in some cases. These findings have important implications for epidemiological analysis and vaccine d esign and demonstrate the need for genetic characterization, rather th an phenotypic characterization using monoclonal antibodies, for the id entification of meningococcal strains.