? Meningococci are classified into serogroups according to their capsular polysaccharides (CP). Of the 13 reported CP groups, 5 (A, B, C, W135, and Y) cause almost all meningococcal disease. These CPs are essential virulence factors because they inhibit the protective actions of complement and are protective antigens because a critical level of serum IgG CP antibodies specifically induces complement mediated lysis of groups A, C, W135, and Y and opsonophagocytic killing of group B meningococci. There are effective CP-based vaccines for groups A, C, W135, and Y but not for group B meningococci or E. coli K1. Compared to groups A, C, W135, and Y, group B meningococci causes a disproportionately large number of infections in infants and young children.? ? Although PSA antibodies bind to many fetal and adult tissues in vitro, there is no evidence for in-vivo binding or associated pathology. Experimental vaccines have been developed that are composed of non-capsular antigens including outer membrane proteins, lipopolysaccharide, iron-binding proteins, and other antigens identified by examination of the organism's DNA. Many of these are polymorphic, heterogeneous, subject to antigenic variation, and may not be representative of all group B meningococci. Further, none will be useful for E. coli K1. Based upon the performance of the Haemophilus influenzae type b, Salmonella typhi (Vi), pneumococcal and group C meningococcal (GCM) vaccines, we developed a PSA conjugate that induced protective levels of serum IgG anti PSA that is simple to produce, easy to standardize and should be close to 100% effective at all ages. Its performance in laboratory mice and primates has been confirmed.? ? Group C meningococcal disease seems to be the most severe among those caused by different meningococcal serogroups. There is no mention of autoimmune diseases, such as Guillain Barre, multiple sclerosis, etc. in published studies of sequelae of group B meningococcal meningitis patients. Our review shows equal or lower rates in nearly every category of sequelae and of mortality associated with group B meningococcal meningitis compared to those of other meningococcal serogroups. There is no epidemiological or clinical evidence to associate pathology with PSA antibodies.? ? We conducted a retrospective cohort study of meningococcal patients to examine evidence for autoimmunity. The entire Danish population constituted our study cohort of 7,467,001 individuals followed for autoimmune disease between 1977 and 2004. Group B meningitis was diagnosed in 2,984 and the control population was 914 patients with group C meningococcal meningitis. Ratios of incidence rates of autoimmune diseases served as a measure of relative risk. Patients with group B meningococcal meningitis, either in comparison with people who had group C meningococcal meningitis or with those that had no history of meningococcal meningitis had no increased risk of autoimmune diseases. This cohort was also studied for a possible increased risk of preterm or stillbirth to women with previous GBM disease, and whether their first-born children were at an increased risk of having birth defects. No such associations were found.? ? These findings suggest that systemic infection with GBM is not associated with autoimmune diseases or with immunoreactive diseases that may affect offspring health, for up to 31 years after meningococcal disease. Further, infants born of mothers who had sustained GBM prior to their pregnancy did have unusual pregnancies or bear children with an increased incidence of birth defects.? ? In a phase 1 study 100 healthy adults will be injected with our PSA conjugate starting in early 2009. This study should be completed by the end of 2009.
| Howitz, Michael F; Simonsen, Jacob; Krause, Tyra Grove et al. (2009) Risk of adverse birth outcome after group B meningococcal disease: results from a Danish national cohort. Pediatr Infect Dis J 28:199-203 |
| Howitz, Michael; Krause, Tyra Grove; Simonsen, Jacob Brunbjerg et al. (2007) Lack of association between group B meningococcal disease and autoimmune disease. Clin Infect Dis 45:1327-34 |
| Stein, Daniel M; Robbins, John; Miller, Mark A et al. (2006) Are antibodies to the capsular polysaccharide of Neisseria meningitidis group B and Escherichia coli K1 associated with immunopathology? Vaccine 24:221-8 |
