Meningococcal B vaccine (4CMenB): the journey from research to real world experience

Abstract

Introduction: Neisseria meningitidis serogroup B (MenB) is the most common cause of bacterial meningitis in many industrialized countries and occurs at any age. The highest incidence is in infants aged <1 year, followed by children and adolescents. Four-component MenB vaccine (4CMenB, Bexsero) is the only MenB vaccine authorized for use in all age-groups. Experience with 4CMenB is growing as it is implemented in different countries/age-groups encompassing university students, children, adolescents, and infant mass vaccination programs. Areas covered: An update of recently available data describing the mechanism of immunogenicity of 4CMenB and real-world evidence of vaccine effectiveness and disease impact. We discuss the appropriate age for vaccination to maximize population impacts. Expert commentary: Invasive meningococcal disease is uncommon and sufficiently powered efficacy studies were not feasible during 4CMenB development. Additionally, several thousand genetically diverse invasive MenB strains circulate globally, varying widely in surface protein expression. This posed significant challenges in predicting clinical protection with MenB vaccines. Five years of 4CMenB use post-licensure confirm the clinical benefit of vaccination as predicted during development. Preliminary evidence suggests an extended impact on other meningococcal serogroups and Neisseria gonorrhoeae.

Multicenter Hospital-Based Prospective Surveillance Study of Bacterial Agents Causing Meningitis and Seroprevalence of Different Serogroups of Neisseria meningitidis, Haemophilus influenzae Type b, and Streptococcus pneumoniae during 2015 to 2018 in Turkey

“…Still, it should be noted that the vaccine targeting serogroup B is only broadly protective and does not cover all strains causing the disease (10). Meningococcal vaccines are serogroup specific or, in the case of the vaccines targeting serogroup B, protein-specific (11). Except for high-risk groups, meningococcal vaccines are not used in routine childhood immunization programs in Turkey, and they have not yet been implemented in the NIP.…”

Potential benefits of using a multicomponent vaccine for prevention of serogroup B meningococcal disease

“…Immunological data have been comprehensively and extensively reviewed elsewhere (Rappuoli et al, 2018;Toneatto et al, 2017;Watson and Turner, 2016). In summary, robust immune responses to each individual component of 4CMenB have been demonstrated in clinical studies across age groups, including in infants, toddlers, and adolescents.…”

“…Despite having been developed independently, both vaccines include factor H binding protein (fHbp) as a major antigenic component. Three distinct variants of fHbp have been described, namely variants 1, 2, and 3, which have been alternatively classified as subfamilies, with subfamily B containing variant 1 and subfamily A containing variants 2 and 3 (Rappuoli et al, 2018). The three variants are immunologically distinct and do not induce cross-protective antibodies, although some low crossreactivity has been evidenced between variants 2 and 3 (Seib et al, 2011).…”

Integrated Bioinformatic Analyses and Immune Characterization of New Neisseria gonorrhoeae Vaccine Antigens Expressed during Natural Mucosal Infection

“…Some protection was shown by antibodies to the gonococcal lipoligosaccharides (LOS) and a porin-based vaccine was also explored [2] but, like pilin, porin is subject to immunological pressure [18][19][20] and also affects complement-dependent bacterial killing [21]. Pre-clinical vaccine studies have been carried out in mouse models of immunization and infection [22,23] using classical surface-exposed antigens (for example, the highly conserved LOS epitope 2C7 [24], transferrin binding proteins (TbpA and TbpB) [25,26]), conserved and/or variable proteins (reviewed in Reference [2]) identified by conventional screenings, reverse vaccinology (initially developed for the Neisseria meningitidis serogroup B vaccine 4CMenB [27,28]), "omics" and bioinformatics [29][30][31][32][33][34][35]. Interest in outer membrane vesicles (OMVs) has been recently renewed by evidence of cross-reactive protection against N. gonorrhoeae by a meningococcal OMV-based vaccine [36][37][38][39].…”