Genetic shifts of Neisseria meningitidis serogroup B antigens and the quest for a broadly cross-protective vaccine

Serogroup B Neisseria meningitidis is the leading cause of meningococcal disease in developed countries. There is currently no vaccine offering wide-ranging protection. Development of a serogroup B polysaccharide-based vaccine has been hindered by potential risks of autoantibodies that cross-react with glycosylated host antigens. A number of subcapsular vaccine candidates, including outer membrane proteins (OMPs), are therefore being investigated. The availability of several meningococcal genome sequences has allowed for a comprehensive analysis of genetic differences occurring within the species. Novel vaccine candidates have been identified by means of reverse vaccinology utilizing the serogroup B meningococcal genome and show promising results for safe and effective vaccines against serogroup B N. meningitidis. The design of protein-based meningococcal vaccines is, however, complicated by the high level of genetic and antigenic diversity exhibited by the meningococcus. N. meningitidis has the capability to change its genome and adapt surface structures to changing environments by a variety of genetic mechanisms. Knowledge of the extent and structuring of this diversity has implications for the use of particular proteins as potential vaccine candidates. In this article, we describe the high degree of genomic variability in N. meningitidis and several of the mechanisms involved. An overview of the implications of antigenic variation of several surface-exposed proteins on their potential vaccine candidacy is provided. The outlook for the quest for broadly cross-protective meningococcal serogroup B vaccine components in the postgenomic era will be discussed.