Prevalence and genetic diversity of candidate vaccine antigens among invasive Neisseria meningitidis isolates in the United States

Preclinical evidence for the potential of a bivalent fHBP vaccine to preventNeisseria meningitidisSerogroup C Disease

“…6 Since these antigens have been demonstrated to be present in other meningococcal serogroups, 8 fHBP-based vaccines have the potential to be pan-meningococcal vaccines. 14 As demonstrated in this study, fHBP is present and expressed on the surface of meningococcal serogroup C isolates, albeit a smaller proportion of isolates than by serogroup B (69% vs. 98%). Moreover, immune sera generated with the bivalent fHBP vaccine killed both serogroup B and C isolates expressing different fHBP variants, thus providing evidence that the bivalent vaccine has the potential to protect across meningococcal serogroups.…”

Role of Factor H Binding Protein in Neisseria meningitidis Virulence and Its Potential as a Vaccine Candidate To Broadly Protect against Meningococcal Disease

“…These observations lead to an interesting proposition that isolates more associated with adolescent carriage or disease in the extreme age groups express fHBP subfamily A proteins, whereas isolates that cause disease in older children and adolescents are more associated with fHBP subfamily B. Though the fHBP gene has been detected in most isolates, the truncated fHBP gene identified by Murphy et al (29) was also identified in MnC isolates (37,42). However, in these MnC isolates, a subpopulation of cells with the mutation appeared to be expressing fHBP on the cell surface, which is suggestive of a compensatory expression mechanism (42).…”

“…South Africa, however, has a higher proportion of subfamily A variants reported (36). Interestingly, in a follow-up study by the Centers for Disease Control and Prevention in the United States, it was found that although there was a lower proportion of disease caused by fHBP subfamily A MnB isolates, infants and subjects Ն65 years of age were more likely to be infected with fHBP subfamily A strains, in contrast to adolescents and young adults, who acquire disease dominated by fHBP subfamily B strains (37). The same study also evaluated the distribution of fHBP proteins in other meningococcal serogroups (MnC, MnY, and MnW135) and showed that for these other serogroups the proportion of fHBP subfamily A variants was also increased.…”

“…The importance of fHBP to N. meningitidis is reflected by the detection of the fHBP gene in essentially all MnB strains examined (29,33,37,44). Of 1,263 U.S. and European MnB invasive strains from a prevalence-based study surveyed for surface expression of fHBP, fewer than 2% did not express fHBP levels above the limit of detection as measured using a universal monoclonal antibody, MN86-994-11, that binds to both subfamilies of fHBP (46).…”

Neuro-Intensive Care of Patients with Acute CNS Infections

“…In pediatric cases 2 months old, group B streptococcus accounts for 86% of cases, and in cases >2 months of age, S. pneumoniae and N. meningitidis are increasingly important causes of bacterial meningitis, with the peak incidence of N. meningitidis in the 11-to 17-year-old age group. Given the rapidly fatal and aggressive course of N. meningitidis infection, ongoing studies to develop a serogroup B vaccine and improve vaccination rates with the current vaccine for serogroups A, C, Y, and W135 continue to be important priorities [14]. In adults >18 years of age, S. pneumoniae infection causes approximately 70% of the cases, followed by N. meningitidis, H. influenzae, group B streptococcus, and L. monocytogenes [5].…”