title: The new multicomponent vaccine against meningococcal serogroup B, 4CMenB: immunological, functional and structural characterization of the antigens.
abstract: Neisseria meningitidis is a major cause of endemic cases and epidemics of meningitis and devastating septicemia. Although effective vaccines exist for several serogroups of pathogenic N. meningitidis, conventional vaccinology approaches have failed to provide a universal solution for serogroup B (MenB) which consequently remains an important burden of disease worldwide. The advent of whole-genome sequencing changed the approach to vaccine development, enabling the identification of potential vaccine candidates starting directly with the genomic information, with a process named reverse vaccinology. The application of reverse vaccinology to MenB allowed the identification of new protein antigens able to induce bactericidal antibodies. Three highly immunogenic antigens (fHbp, NadA and NHBA) were combined with outer membrane vesicles and formulated for human use in a multicomponent vaccine, named 4CMenB. This is the first MenB vaccine based on recombinant proteins able to elicit a robust bactericidal immune response in adults, adolescents and infants against a broad range of serogroup B isolates. This review describes the successful story of the development of the 4CMenB vaccine, with particular emphasis on the functional, immunological and structural characterization of the protein antigens included in the vaccine.
authors.affiliation: Novartis Vaccines and Diagnostics, Via Fiorentina 1, 53100 Siena, Italy. davide.serruto@novartis.com
authors.forename: Davide
authors.initials: D
authors.lastname: Serruto
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Bottomley
authors.forename: Sanjay
authors.initials: S
authors.lastname: Ram
authors.forename: Marzia M
authors.initials: MM
authors.lastname: Giuliani
authors.forename: Rino
authors.initials: R
authors.lastname: Rappuoli
mesh_terms: D018829:Adhesins, Bacterial / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000942:Antigens, Bacterial / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006801:Humans; D022401:Meningococcal Vaccines / Q000235:genetics / Q000276:immunology*; D038541:Neisseria meningitidis, Serogroup B / Q000235:genetics* / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology
chemical_list: C570015:4CMenB vaccine; D018829:Adhesins, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D022401:Meningococcal Vaccines; C501982:NadA protein, Neisseria meningitidis; D014614:Vaccines, Synthetic; C484699:factor H-binding protein, Neisseria meningitidis