Abstract
ABSTRACTThe widespread use of meningococcal polysaccharide conjugate vaccines has highlighted the challenge of providing protection against serogroup B disease. Over a period of 4 decades, vaccine development has focused on subcapsular protein antigens, first with outer membrane vesicle (OMV) vaccines against epidemic outbreaks, and more recently on new multicomponent vaccines designed to offer better cross-protection against the antigenically diverse strains responsible for endemic disease. Because of the low incidence of meningococcal disease, the protective efficacy of these vaccines has not been determined in clinical studies, and their licensure has been based on serological data; however, the serological assays used to predict protective coverage have limitations. As a result, evidence of the effectiveness of these vaccines against different strains and the contribution of specific antigens to protection can only be provided by epidemiological analyses following their implementation in sufficiently large populations. The recent inclusion of the four-component meningococcal serogroup B (4CMenB) vaccine, Bexsero, in the infant immunization program in the UK has provided preliminary evidence that the vaccine is effective. Ongoing surveillance will provide valuable data on its longer-term impact and antigenic coverage. Further development of protein-based vaccines against meningococcal disease is anticipated to improve antigenic coverage and adjust to changes in circulating strains. At the same time, alternative immunization strategies may be explored to improve overall vaccine effectiveness by, for example, protecting the youngest infants or providing herd protection.
Highlights
Clinical and Vaccine ImmunologyIn 2013, the European Commission approved the four-component meningococcal serogroup B (4CMenB) vaccine, Bexsero (GSK)
The widespread use of meningococcal polysaccharide conjugate vaccines has highlighted the challenge of providing protection against serogroup B disease
Both contain the meningococcal complement factor H binding protein (FHbp), which had been identified as a candidate antigen by independent vaccine development programs at GSK in Italy and Pfizer in the United States
Summary
In 2013, the European Commission approved the four-component meningococcal serogroup B (4CMenB) vaccine, Bexsero (GSK) This and the bivalent recombinant lipoprotein (rLP2086) vaccine, Trumenba, have subsequently been used prior to licensure in the United States, under investigational new drug applications, to respond to outbreaks of serogroup B disease among university students. IMMUNE EVASION Since the meningococcus belongs to the normal microbiome of the human nasopharynx and is not known to have any other habitat, it is highly adapted to a commensal lifestyle and has evolved to evade host immunity This has been a confounding factor in vaccine development. In addition to the various capsule and LPS structures, subcapsular outer membrane proteins and lipoproteins are often highly antigenically variable as a consequence of diversifying selection driven by host immunity They may be downregulated or switched off when they are not required so as not to be a target of the immune response.
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