1,813
Views
56
CrossRef citations to date
0
Altmetric
Review

Neisseria meningitidis factor H-binding protein fHbp: a key virulence factor and vaccine antigen

, , , &

References

  • Stephens DS, Greenwood B, Brandtzaeg P. Epidemic meningitis, meningococcaemia, and Neisseria meningitidis. Lancet 2007;369(9580):2196-210
  • Boisier P, Nicolas P, Djibo S, et al. Meningococcal meningitis: unprecedented incidence of serogroup X-related cases in 2006 in Niger. Clin Infect Dis 2007;44(5):657-63
  • Zimmer SM, Stephens DS. Meningococcal conjugate vaccines. Expert Opin Pharmacother 2004;5(4):855-63
  • Keyserling H, Papa T, Koranyi K, et al. Safety, immunogenicity, and immune memory of a novel meningococcal (groups A, C, Y, and W-135) polysaccharide diphtheria toxoid conjugate vaccine (MCV-4) in healthy adolescents. Arch Pediatr Adolesc Med 2005;159(10):907-13
  • Cooper B, DeTora L, Stoddard J. Menveo®: a novel quadrivalent meningococcal CRM197 conjugate vaccine against serogroups A, C, W-135 and Y. Expert Rev Vaccines 2011;10(1):21-33
  • Finne J, Bitter-Suermann D, Goridis C, et al. An IgG monoclonal antibody to group B meningococci cross-reacts with developmentally regulated polysialic acid units of glycoproteins in neural and extraneural tissues. J Immunol 1987;138(12):4402-7
  • Pizza M, Scarlato V, Masignani V, et al. Identification of vaccine candidates against serogroup B meningococcus by whole-genome sequencing. Science 2000;287(5459):1816-20
  • Masignani V, Comanducci M, Giuliani MM, et al. Vaccination against Neisseria meningitidis using three variants of the lipoprotein GNA1870. J Exp Med 2003;197(6):789-99
  • Fletcher LD, Bernfield L, Barniak V, et al. Vaccine potential of the Neisseria meningitidis 2086 lipoprotein. Infect Immun 2004;72(4):2088-100
  • Madico G, Welsch JA, Lewis LA, et al. The meningococcal vaccine candidate GNA1870 binds the complement regulatory protein factor H and enhances serum resistance. J Immunol 2006;177(1):501-10
  • Ferreira VP, Pangburn MK, Cortes C. Complement control protein factor H: the good, the bad, and the inadequate. Mol Immunol 2010;47(13):2187-97
  • Meri S, Jordens M, Jarva H. Microbial complement inhibitors as vaccines. Vaccine 2008;26(Suppl 8):I113-17
  • Seib KL, Serruto D, Oriente F, et al. Factor H-binding protein is important for meningococcal survival in human whole blood and serum and in the presence of the antimicrobial peptide LL-37. Infect Immun 2009;77(1):292-9
  • Welsch JA, Ram S, Koeberling O, et al. Complement-dependent synergistic bactericidal activity of antibodies against factor H-binding protein, a sparsely distributed meningococcal vaccine antigen. J Infect Dis 2008;197(7):1053-61
  • Veggi D, Gentile MA, Cantini F, et al. The factor H binding protein of Neisseria meningitidis interacts with xenosiderophores in vitro. Biochemistry 2012;51(46):9384-93
  • Giuliani MM, Adu-Bobie J, Comanducci M, et al. A universal vaccine for serogroup B meningococcus. Proc Natl Acad Sci USA 2006;103(29):10834-9
  • O’Ryan M, Stoddard J, Toneatto D, et al. A multi-component meningococcal serogroup B vaccine (4CMenB): the clinical development program. Drugs 2014;74(1):15-30
  • Zlotnick GW, Jones TR, Liberator P, et al. The discovery and development of a novel vaccine to protect against Neisseria meningitidis serogroup B disease. Hum Vaccin Immunother 2015;11(1):5-13
  • Delany I, Rappuoli R, Seib KL. Vaccines, reverse vaccinology, and bacterial pathogenesis. Cold Spring Harb Perspect Med 2013;3(5):a012476
  • McNeil LK, Zagursky RJ, Lin SL, et al. Role of factor H binding protein in Neisseria meningitidis virulence and its potential as a vaccine candidate to broadly protect against meningococcal disease. Microbiol Mol Biol Rev 2013;77(2):234-52
  • Pizza M, Donnelly J, Rappuoli R. Factor H-binding protein, a unique meningococcal vaccine antigen. Vaccine 2008;26(Suppl 8):I46-8
  • Brehony C, Wilson DJ, Maiden MC. Variation of the factor H-binding protein of Neisseria meningitidis. Microbiology 2009;155(Pt 12):4155-69
  • Jiang HQ, Hoiseth SK, Harris SL, et al. Broad vaccine coverage predicted for a bivalent recombinant factor H binding protein based vaccine to prevent serogroup B meningococcal disease. Vaccine 2010;28(37):6086-93
  • Mascioni A, Bentley BE, Camarda R, et al. Structural Basis for the Immunogenic Properties of the Meningococcal Vaccine Candidate LP2086. J Biol Chem 2009;284(13):8738-46
  • Available from: http://pubmlst.org/neisseria/fHbp/
  • Beernink PT, Granoff DM. The modular architecture of meningococcal factor H-binding protein. Microbiology 2009;155(Pt 9):2873-83
  • Pajon R, Beernink PT, Harrison LH, et al. Frequency of factor H-binding protein modular groups and susceptibility to cross-reactive bactericidal activity in invasive meningococcal isolates. Vaccine 2010;28(9):2122-9
  • Bambini S, Muzzi A, Olcen P, et al. Distribution and genetic variability of three vaccine components in a panel of strains representative of the diversity of serogroup B meningococcus. Vaccine 2009;27(21):2794-803
  • Murphy E, Andrew L, Lee KL, et al. Sequence diversity of the factor H binding protein vaccine candidate in epidemiologically relevant strains of serogroup B Neisseria meningitidis. J Infect Dis 2009;200(3):379-89
  • Beernink PT, Welsch JA, Harrison LH, et al. Prevalence of factor H-binding protein variants and NadA among meningococcal group B isolates from the United States: implications for the development of a multicomponent group B vaccine. J Infect Dis 2007;195(10):1472-9
  • Hoiseth SK, Murphy E, Andrew L, et al. A multi-country evaluation of Neisseria meningitidis serogroup B factor H-binding proteins and implications for vaccine coverage in different age groups. Pediatr Infect Dis J 2013;32(10):1096-101
  • Wang X, Cohn A, Comanducci M, et al. Prevalence and genetic diversity of candidate vaccine antigens among invasive Neisseria meningitidis isolates in the United States. Vaccine 2011;29(29-30):4739-44
  • Marsh JW, Shutt KA, Pajon R, et al. Diversity of factor H-binding protein in Neisseria meningitidis carriage isolates. Vaccine 2011;29(35):6049-58
  • Muzzi A, Mora M, Pizza M, et al. Conservation of meningococcal antigens in the genus Neisseria. MBio 2013;4(3):e00163-13
  • Lucidarme J, Gilchrist S, Newbold LS, et al. Genetic distribution of noncapsular meningococcal group B vaccine antigens in Neisseria lactamica. Clin Vaccine Immunol 2013;20(9):1360-9
  • Jongerius I, Lavender H, Tan L, et al. Distinct binding and immunogenic properties of the gonococcal homologue of meningococcal factor h binding protein. PLoS Pathog 2013;9(8):e1003528
  • Lucidarme J, Tan L, Exley RM, et al. Characterization of Neisseria meningitidis isolates that do not express the virulence factor and vaccine antigen factor H binding protein. Clin Vaccine Immunol 2011;18(6):1002-14
  • Seib KL, Oriente F, Adu-Bobie J, et al. Influence of serogroup B meningococcal vaccine antigens on growth and survival of the meningococcus in vitro and in ex vivo and in vivo models of infection. Vaccine 2010;28(12):2416-27
  • Sanders H, Brehony C, Maiden MC, et al. The effect of iron availability on transcription of the Neisseria meningitidis fHbp gene varies among clonal complexes. Microbiology 2012;158(Pt 4):869-76
  • Oriente F, Scarlato V, Delany I. Expression of factor H binding protein of meningococcus responds to oxygen limitation through a dedicated FNR-regulated promoter. J Bacteriol 2010;192(3):691-701
  • Echenique-Rivera H, Muzzi A, Del Tordello E, et al. Transcriptome analysis of Neisseria meningitidis in human whole blood and mutagenesis studies identify virulence factors involved in blood survival. PLoS Pathog 2011;7(5):e1002027
  • Hedman AK, Li MS, Langford PR, et al. Transcriptional profiling of serogroup B Neisseria meningitidis growing in human blood: an approach to vaccine antigen discovery. PLoS One 2012;7(6):e39718
  • Litt DJ, Savino S, Beddek A, et al. Putative vaccine antigens from Neisseria meningitidis recognized by serum antibodies of young children convalescing after meningococcal disease. J Infect Dis 2004;190(8):1488-97
  • Jacobsson S, Molling P, Olcen P. Seroprevalence of antibodies against fHbp and NadA, two potential vaccine antigens for Neisseria meningitidis. Vaccine 2009;27(42):5755-9
  • Ala’aldeen DA, Flint M, Oldfield NJ, et al. Human antibody responses to the meningococcal factor H binding protein (LP2086) during invasive disease, colonization and carriage. Vaccine 2010;28(48):7667-75
  • Haralambous E, Weiss HA, Radalowicz A, et al. Sibling familial risk ratio of meningococcal disease in UK Caucasians. Epidemiol Infect 2003;130(3):413-18
  • Lewis LA, Ram S. Meningococcal disease and the complement system. Virulence 2014;5(1):98-126
  • Granoff DM, Welsch JA, Ram S. Binding of complement factor H (fH) to Neisseria meningitidis is specific for human fH and inhibits complement activation by rat and rabbit sera. Infect Immun 2009;77(2):764-9
  • Vu DM, Shaughnessy J, Lewis LA, et al. Enhanced bacteremia in human factor H transgenic rats infected by Neisseria meningitidis. Infect Immun 2012;80(2):643-50
  • Konar M, Granoff DM, Beernink PT. Importance of inhibition of binding of complement factor H for serum bactericidal antibody responses to meningococcal factor H-binding protein vaccines. J Infect Dis 2013;208(4):627-36
  • Giuntini S, Beernink PT, Reason DC, et al. Monoclonal antibodies to meningococcal factor H binding protein with overlapping epitopes and discordant functional activity. PLoS One 2012;7(3):e34272
  • Giuntini S, Reason DC, Granoff DM. Complement-mediated bactericidal activity of anti-factor H binding protein monoclonal antibodies against the meningococcus relies upon blocking factor H binding. Infect Immun 2011;79(9):3751-9
  • Giuntini S, Reason DC, Granoff DM. Combined roles of human IgG subclass, alternative complement pathway activation, and epitope density in the bactericidal activity of antibodies to meningococcal factor H binding protein. Infect Immun 2012;80(1):187-94
  • Beernink PT, Shaughnessy J, Braga EM, et al. A meningococcal factor H binding protein mutant that eliminates factor H binding enhances protective antibody responses to vaccination. J Immunol 2011;186(6):3606-14
  • Beernink PT, Shaughnessy J, Pajon R, et al. The effect of human factor H on immunogenicity of meningococcal native outer membrane vesicle vaccines with over-expressed factor H binding protein. PLoS Pathog 2012;8(5):e1002688
  • Pajon R, Beernink PT, Granoff DM. Design of meningococcal factor H binding protein mutant vaccines that do not bind human complement factor H. Infect Immun 2012;80(8):2667-77
  • Rossi R, Granoff DM, Beernink PT. Meningococcal factor H-binding protein vaccines with decreased binding to human complement factor H have enhanced immunogenicity in human factor H transgenic mice. Vaccine 2013;31(46):5451-7
  • van der Veen S, Johnson S, Jongerius I, et al. Nonfunctional variant 3 factor H binding proteins as meningococcal vaccine candidates. Infect Immun 2014;82(3):1157-63
  • Costa I, Pajon R, Granoff DM. Human factor H (FH) impairs protective meningococcal anti-FHbp antibody responses and the antibodies enhance FH binding. MBio 2014;5(5):e01625-14
  • Bambini S, Piet J, Muzzi A, et al. An analysis of the sequence variability of meningococcal fHbp, NadA and NHBA over a 50-year period in the Netherlands. PLoS One 2013;8(5):e65043
  • Holst J, Comanducci M, Bambini S, et al. Variability of genes encoding surface proteins used as vaccine antigens in meningococcal endemic and epidemic strain panels from Norway. Vaccine 2014;32(23):2722-31
  • Lewis LA, Ngampasutadol J, Wallace R, et al. The meningococcal vaccine candidate neisserial surface protein A (NspA) binds to factor H and enhances meningococcal resistance to complement. PLoS Pathog 2010;6(7):e1001027
  • Giuntini S, Vu DM, Granoff DM. fH-dependent complement evasion by disease-causing meningococcal strains with absent fHbp genes or frameshift mutations. Vaccine 2013;31(38):4192-9
  • Lewis LA, Carter M, Ram S. The relative roles of factor H binding protein, neisserial surface protein A, and lipooligosaccharide sialylation in regulation of the alternative pathway of complement on meningococci. J Immunol 2012;188(10):5063-72
  • Lewis LA, Vu DM, Vasudhev S, et al. Factor H-dependent alternative pathway inhibition mediated by porin B contributes to virulence of Neisseria meningitidis. MBio 2013;4(5):e00339-13
  • Cantini F, Veggi D, Dragonetti S, et al. Solution structure of the factor H-binding protein, a survival factor and protective antigen of Neisseria meningitidis. J Biol Chem 2009;284(14):9022-6
  • Cendron L, Veggi D, Girardi E, et al. Structure of the uncomplexed Neisseria meningitidis factor H-binding protein fHbp (rLP2086). Acta Crystallogr Sect F Struct Biol Cryst Commun 2011;67(Pt 5):531-5
  • Johnson S, Tan L, van der Veen S, et al. Design and evaluation of meningococcal vaccines through structure-based modification of host and pathogen molecules. PLoS Pathog 2012;8(10):e1002981
  • Mascioni A, Moy FJ, McNeil LK, et al. NMR dynamics and antibody recognition of the meningococcal lipidated outer membrane protein LP2086 in micellar solution. Biochim Biophys Acta 2010;1798(2):87-93
  • Bessler WG, Jung G. Synthetic lipopeptides as novel adjuvants. Res Immunol 1992;143(5):548-53; discussion 79-80
  • Schneider MC, Prosser BE, Caesar JJ, et al. Neisseria meningitidis recruits factor H using protein mimicry of host carbohydrates. Nature 2009;458(7240):890-3
  • Beernink PT, Welsch JA, Bar-Lev M, et al. Fine antigenic specificity and cooperative bactericidal activity of monoclonal antibodies directed at the meningococcal vaccine candidate factor h-binding protein. Infect Immun 2008;76(9):4232-40
  • Beernink PT, LoPasso C, Angiolillo A, et al. A region of the N-terminal domain of meningococcal factor H-binding protein that elicits bactericidal antibody across antigenic variant groups. Mol Immunol 2009;46(8-9):1647-53
  • Scarselli M, Cantini F, Santini L, et al. Epitope mapping of a bactericidal monoclonal antibody against the factor H binding protein of Neisseria meningitidis. J Mol Biol 2009;386(1):97-108
  • Malito E, Faleri A, Lo Surdo P, et al. Defining a protective epitope on factor H binding protein, a key meningococcal virulence factor and vaccine antigen. Proc Natl Acad Sci USA 2013;110(9):3304-9
  • Faleri A, Santini L, Brier S, et al. Two cross-reactive monoclonal antibodies recognize overlapping epitopes on Neisseria meningitidis factor H binding protein but have different functional properties. FASEB J 2013;28(4):1644-53
  • Vu DM, Pajon R, Reason DC, et al. A broadly cross-reactive monoclonal antibody against an epitope on the n-terminus of meningococcal fHbp. Sci Rep 2012;2:341
  • Giuliani MM, Santini L, Brunelli B, et al. The region comprising amino acids 100 to 255 of Neisseria meningitidis lipoprotein GNA 1870 elicits bactericidal antibodies. Infect Immun 2005;73(2):1151-60
  • Scarselli M, Arico B, Brunelli B, et al. Rational design of a meningococcal antigen inducing broad protective immunity. Sci Transl Med 2011;3(91):91ra62
  • Shaughnessy J, Lewis LA, Jarva H, et al. Functional comparison of the binding of factor H short consensus repeat 6 (SCR 6) to factor H binding protein from Neisseria meningitidis and the binding of factor H SCR 18 to 20 to Neisseria gonorrhoeae porin. Infect Immun 2009;77(5):2094-103
  • Hong E, Giorgini D, Deghmane AE, et al. Functional impacts of the diversity of the meningococcal factor H binding protein. Vaccine 2012;31(1):183-9
  • Lex A, Wiesmuller KH, Jung G, et al. A synthetic analogue of Escherichia coli lipoprotein, tripalmitoyl pentapeptide, constitutes a potent immune adjuvant. J Immunol 1986;137(8):2676-81
  • Pajon R, Fergus AM, Granoff DM. Mutant native outer membrane vesicles combined with a Serogroup A polysaccharide conjugate vaccine for prevention of meningococcal epidemics in Africa. PLoS One 2013;8(6):e66536
  • Koeberling O, Delany I, Granoff DM. A critical threshold of meningococcal factor H binding protein expression is required for increased breadth of protective antibodies elicited by native outer membrane vesicle vaccines. Clin Vaccine Immunol 2011;18(5):736-42
  • Koeberling O, Seubert A, Santos G, et al. Immunogenicity of a meningococcal native outer membrane vesicle vaccine with attenuated endotoxin and over-expressed factor H binding protein in infant rhesus monkeys. Vaccine 2011;29(29-30):4728-34
  • Keiser PB, Biggs-Cicatelli S, Moran EE, et al. A phase 1 study of a meningococcal native outer membrane vesicle vaccine made from a group B strain with deleted lpxL1 and synX, over-expressed factor H binding protein, two PorAs and stabilized OpcA expression. Vaccine 2011;29(7):1413-20
  • Findlow J, Borrow R, Snape MD, et al. Multicenter, open-label, randomized phase II controlled trial of an investigational recombinant meningococcal serogroup B vaccine with and without outer membrane vesicles, administered in infancy. Clin Infect Dis 2010;51(10):1127-37
  • Wedege E, Bolstad K, Aase A, et al. Functional and specific antibody responses in adult volunteers in New Zealand who were given one of two different meningococcal serogroup B outer membrane vesicle vaccines. Clin Vaccine Immunol 2007;14(7):830-8
  • Vogel U, Taha MK, Vazquez JA, et al. Predicted strain coverage of a meningococcal multicomponent vaccine (4CMenB) in Europe: a qualitative and quantitative assessment. Lancet Infect Dis 2013;13(5):416-25
  • Brunelli B, Del Tordello E, Palumbo E, et al. Influence of sequence variability on bactericidal activity sera induced by Factor H binding protein variant 1.1. Vaccine 2011;29(5):1072-81
  • Capecchi B, Adu-Bobie J, Di Marcello F, et al. Neisseria meningitidis NadA is a new invasin which promotes bacterial adhesion to and penetration into human epithelial cells. Mol Microbiol 2005;55(3):687-98
  • Comanducci M, Bambini S, Brunelli B, et al. NadA, a novel vaccine candidate of Neisseria meningitidis. J Exp Med 2002;195(11):1445-54
  • Metruccio MM, Pigozzi E, Roncarati D, et al. A novel phase variation mechanism in the meningococcus driven by a ligand-responsive repressor and differential spacing of distal promoter elements. PLoS Pathog 2009;5(12):e1000710
  • Fagnocchi L, Biolchi A, Ferlicca F, et al. Transcriptional regulation of the nadA gene in Neisseria meningitidis impacts the prediction of coverage of a multicomponent meningococcal serogroup B vaccine. Infect Immun 2013;81(2):560-9
  • Fagnocchi L, Pigozzi E, Scarlato V, et al. In the NadR regulon, adhesins and diverse meningococcal functions are regulated in response to signals in human saliva. J Bacteriol 2012;194(2):460-74
  • Serruto D, Spadafina T, Ciucchi L, et al. Neisseria meningitidis GNA2132, a heparin-binding protein that induces protective immunity in humans. Proc Natl Acad Sci USA 2010;107(8):3770-5
  • Anderson AS, Hao L, Jiang Q, et al. Potential impact of the bivalent rLP2806 vaccine on Neisseria meningitidis carriage and invasive serogroup B disease. Hum Vaccin Immunother 2012;9(3):471-9
  • Seib KL, Brunelli B, Brogioni B, et al. Characterisation of diverse sub-variants of the meningococcal factor H binding protein (fHbp) for their ability to bind fH, mediate serum resistance and induce bactericidal antibodies. Infect Immun 2011;79(2):970-81
  • Brehony C, Jolley KA, Maiden MC. Multilocus sequence typing for global surveillance of meningococcal disease. FEMS Microbiol Rev 2007;31(1):15-26
  • Donnelly J, Medini D, Boccadifuoco G, et al. Qualitative and quantitative assessment of meningococcal antigens to evaluate the potential strain coverage of protein-based vaccines. Proc Natl Acad Sci USA 2010;107(45):19490-5
  • Plikaytis BD, Stella M, Boccadifuoco G, et al. Inter-laboratory standardization of the sandwich ELISA designed for MATS, a rapid, reproducible method for estimating the strain coverage of investigational vaccines. Clin Vaccine Immunol 2012;19(10):1609-17
  • Perez-Trallero E, Esnal O, Marimon JM. Progressive decrease in the potential usefulness of Meningococcal Serogroup B vaccine (4CMenB, Bexsero(R)) in Gipuzkoa, Northern Spain. PLoS One 2014;9(12):e116024
  • Frosi G, Biolchi A, Lo Sapio M, et al. Bactericidal antibody against a representative epidemiological meningococcal serogroup B panel confirms that MATS underestimates 4CMenB vaccine strain coverage. Vaccine 2013;31(43):4968-74
  • Goldschneider I, Gotschlich EC, Artenstein MS. Human immunity to the meningococcus. II. Development of natural immunity. J Exp Med 1969;129(6):1327-48
  • Frasch CE, Borrow R, Donnelly J. Bactericidal antibody is the immunologic surrogate of protection against meningococcal disease. Vaccine 2009;27(Suppl 2):B112-16
  • Borrow R, Carlone GM, Rosenstein N, et al. Neisseria meningitidis group B correlates of protection and assay standardization–international meeting report Emory University, Atlanta, Georgia, United States, 16-17 March 2005. Vaccine 2006;24(24):5093-107
  • Giuliani MM, Biolchi A, Serruto D, et al. Measuring antigen-specific bactericidal responses to a multicomponent vaccine against serogroup B meningococcus. Vaccine 2010;28(31):5023-30
  • Vesikari T, Esposito S, Prymula R, et al. Immunogenicity and safety of an investigational multicomponent, recombinant, meningococcal serogroup B vaccine (4CMenB) administered concomitantly with routine infant and child vaccinations: results of two randomised trials. Lancet 2013;381(9869):825-35
  • Santolaya ME, O’Ryan ML, Valenzuela MT, et al. Immunogenicity and tolerability of a multicomponent meningococcal serogroup B (4CMenB) vaccine in healthy adolescents in Chile: a phase 2b/3 randomised, observer-blind, placebo-controlled study. Lancet 2012;379(9816):617-24
  • Snape MD, Dawson T, Oster P, et al. Immunogenicity of two investigational serogroup B meningococcal vaccines in the first year of life: a randomized comparative trial. Pediatr Infect Dis J 2010;29(11):e71-9
  • Gossger N, Snape MD, Yu LM, et al. Immunogenicity and tolerability of recombinant serogroup B meningococcal vaccine administered with or without routine infant vaccinations according to different immunization schedules: a randomized controlled trial. JAMA 2012;307(6):573-82
  • Holst J, Oster P, Arnold R, et al. Vaccines against meningococcal serogroup B disease containing outer membrane vesicles (OMV): lessons from past programs and implications for the future. Hum Vaccin Immunother 2013;9(6):1241-53
  • Esposito S, Prymula R, Zuccotti GV, et al. A phase 2 randomized controlled trial of a multicomponent meningococcal serogroup B vaccine, 4CMenB, in infants (II). Hum Vaccin Immunother 2014;10(7):2005-14
  • Prymula R, Esposito S, Zuccotti GV, et al. A phase 2 randomized controlled trial of a multicomponent meningococcal serogroup B vaccine (I): effects of prophylactic paracetamol on immunogenicity and reactogenicity of routine infant vaccines and 4CMenB. Hum Vaccin Immunother 2014;10(7):1993-2004
  • Kimura A, Toneatto D, Kleinschmidt A, et al. Immunogenicity and safety of a multicomponent meningococcal serogroup B vaccine and a quadrivalent meningococcal CRM197 conjugate vaccine against serogroups A, C, W-135, and Y in adults who are at increased risk for occupational exposure to meningococcal isolates. Clin Vaccine Immunol 2011;18(3):483-6
  • Snape MD, Saroey P, John TM, et al. Persistence of bactericidal antibodies following early infant vaccination with a serogroup B meningococcal vaccine and immunogenicity of a preschool booster dose. CMAJ 2013;185(15):E715-24
  • McQuaid F, Snape MD, John TM, et al. Persistence of bactericidal antibodies to 5 years of age after immunization with serogroup B meningococcal vaccines at 6, 8, 12 and 40 months of age. Pediatr Infect Dis J 2014;33(7):760-6
  • Santolaya ME, O’Ryan M, Valenzuela MT, et al. Persistence of antibodies in adolescents 18-24 months after immunization with one, two, or three doses of 4CMenB meningococcal serogroup B vaccine. Hum Vaccin Immunother 2013;9(11):2304-10
  • Read RC, Baxter D, Chadwick DR, et al. Effect of a quadrivalent meningococcal ACWY glycoconjugate or a serogroup B meningococcal vaccine on meningococcal carriage: an observer-blind, phase 3 randomised clinical trial. Lancet 2014;384(9960):2123-31
  • Maiden MC, Stuart JM. Carriage of serogroup C meningococci 1 year after meningococcal C conjugate polysaccharide vaccination. Lancet 2002;359(9320):1829-31
  • EMA. European Medicines Agency (EMA) Authorization Details for Bexsero. 2013. Available from: http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/002333/human_med_001614.jsp&mid=WC0b01ac058001d124 [Accessed September 2014]
  • Health_Canada. Health Canada Authorization Details for Bexsero. 2014. Available from: http://www.hc-sc.gc.ca/dhp-mps/prodpharma/sbd-smd/drug-med/sbd_smd_2014_bexsero_147275-eng.php [Accessed September 2014]
  • TGA. Australian Therapeutic Goods Administration (TGA) Authorization Details for Bexsero. 2013. Available from: http://www.tga.gov.au/pdf/auspar/auspar-meningococcal-131031.pdf [Accessed September 2014]
  • CDC. Centers for Disease Control and Prevention (CDC). Serogroup B Meningococcal Vaccine & Outbreaks (Dec 2013, Jan 2014). 2014. Available from: http://www.cdc.gov/meningococcal/outbreaks/ucsb.html [Accessed September 2014]
  • NVD. Meningitis B (MenB) Vaccination Programs at Princeton University and University of California, Santa Barbara (UCSB), Novartis Vaccines and DIagnostics (NVD), Media Release. 2014. Available from: https://http://www.novartisvaccines.com/newsroom/university-outbreaks.shtml [Accessed September 2014]
  • Patel M. Use of a Novel Serogroup B Meningococcal Vaccine in Response to Two University Outbreaks in the US. XIX International Pathogenic Neisseria Conference (Oral Presentation no O22); Ashville, NC, USA; 2014
  • Sheldon E, Schwartz H, Jiang Q, et al. A phase 1, randomized, open-label, active-controlled trial to assess the safety of a meningococcal serogroup B bivalent rLP2086 vaccine in healthy adults. Hum Vaccin Immunother 2012;8(7):888-95
  • Richmond PC, Nissen MD, Marshall HS, et al. A bivalent Neisseria meningitidis recombinant lipidated factor H binding protein vaccine in young adults: results of a randomised, controlled, dose-escalation phase 1 trial. Vaccine 2012;30(43):6163-74
  • Marshall HS, Richmond PC, Nissen MD, et al. Safety and immunogenicity of a meningococcal B bivalent rLP2086 vaccine in healthy toddlers aged 18-36 months: a phase 1 randomized-controlled clinical trial. Pediatr Infect Dis J 2012;31(10):1061-8
  • Richmond PC, Marshall HS, Nissen MD, et al. Safety, immunogenicity, and tolerability of meningococcal serogroup B bivalent recombinant lipoprotein 2086 vaccine in healthy adolescents: a randomised, single-blind, placebo-controlled, phase 2 trial. Lancet Infect Dis 2012;12(8):597-607
  • Available from: www.clinicaltrials.gov
  • Martinon-Torres F, Gimenez-Sanchez F, Bernaola-Iturbe E, et al. A randomized, phase 1/2 trial of the safety, tolerability, and immunogenicity of bivalent rLP2086 meningococcal B vaccine in healthy infants. Vaccine 2014;32(40):5206-11
  • FDA. Trumenba Package Insert. 2014. Available from: http://www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM421139.pdf
  • EMA. Bexsero. Summary Of Product Characteristics. 2014. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002333/WC500137881.pdf
  • Toneatto D, Ismaili S, Ypma E, et al. The first use of an investigational multicomponent meningococcal serogroup B vaccine (4CMenB) in humans. Hum Vaccin 2011;7(6):646-53
  • Safety, Tolerability and Immunogenicity of Three Doses of Novartis Meningococcal B Vaccine When Administered to Healthy At-risk Adults. Available from: https://www.clinicaltrials.gov/ct2/show/NCT00560313
  • Safety, Tolerability and Immunogenicity of Novartis Meningococcal B Recombinant Vaccine Administered to Healthy Adolescents According to Different Vaccination Schedules. Available from: https://clinicaltrials.gov/ct2/show/NCT00661713
  • Assessment of Antibody Persistence at Eighteen Months After the Completion of the Vaccination Course in Study V72P10. Available from: https://clinicaltrials.gov/ct2/show/NCT01148524
  • Novartis Vaccine and Diagnostics Carriage Trial. Available from: https://clinicaltrials.gov/ct2/show/NCT01214850
  • Prevention, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study. Available from: https://clinicaltrials.gov/ct2/show/NCT00381615
  • Safety, Tolerability and Immunogenicity of Two Different Formulations of MenB Vaccine, When Administered to Healthy Infants. Available from: https://clinicaltrials.gov/ct2/show/NCT00433914
  • Extension Study Evaluating Antibody Persistence and Safety, Tolerability and Immunogenicity of Booster Doses of Novartis rMenB±OMV NZ Vaccine in Healthy UK Children Who Previously Received One or Four Doses of the Same Vaccine. Available from: https://www.clinicaltrials.gov/ct2/show/NCT01027351
  • Safety and Immunogenicity in Dose-Ranging and Formulation-Finding Meningococcal B (MenB) Vaccine Study in 2-month-old Infants. Available from: https://clinicaltrials.gov/ct2/show/NCT00937521
  • Safety, Tolerability and Immunogenicity of Meningococcal B Recombinant Vaccine Administered With or Without Routine Infant Vaccinations to Healthy Infants According to Different Immunization Schedules. Available from: https://clinicaltrials.gov/ct2/show/NCT00721396
  • Immunogenicity, Safety and Lot to Lot Consistency of Novartis Meningococcal B Recombinant Vaccine When Administered With Routine Infant Vaccinations to Healthy Infants. Available from: https://clinicaltrials.gov/ct2/show/NCT00657709
  • Extension Study of V72P13 to Evaluate the Safety, Tolerability and Immunogenicity of Novartis Meningococcal B Recombinant Vaccine When Administered as a Booster or as a Two-dose Catch-up to Healthy Toddlers. Available from: https://clinicaltrials.gov/ct2/show/NCT00847145
  • Study Evaluating Safety And Tolerability Of Meningococcal B Rlp2086 Vaccine In Healthy Adults. Available from: https://clinicaltrials.gov/ct2/show/NCT00879814
  • Study Evaluating the Safety, Immunogenicity and Tolerability of Meningococcal Group B Vaccine in Healthy Adults. Available from: https://clinicaltrials.gov/ct2/show/NCT00297687
  • A Study Evaluating Safety And Immunogenicity Of Meningococcal B Rlp2086 Vaccine In Adolescents. Available from: https://clinicaltrials.gov/ct2/show/NCT00808028
  • Safety and Blood Collection Study Of Meningococcal B Rlp2086 Vaccine In Adults. Available from: https://clinicaltrials.gov/ct2/show/NCT00780806
  • Marshall HS, Richmond PC, Nissen MD, et al. A phase 2 open-label safety and immunogenicity study of a meningococcal B bivalent rLP2086 vaccine in healthy adults. Vaccine 2013;31(12):1569-75
  • Study Evaluating Safety & Immunogenicity of rLP2086 Vaccine in Adolescents. Available from: https://clinicaltrials.gov/ct2/show/NCT00387725
  • Nissen MD, Marshall HS, Richmond PC, et al. A randomized, controlled, phase 1/2 trial of a Neisseria meningitidis serogroup B bivalent rLP2086 vaccine in healthy children and adolescents. Pediatr Infect Dis J 2012;32(4):364-71
  • Study Evaluating Safety & Immunogenicity of rLP2086 Vaccine in Healthy Toddlers. Available from: https://clinicaltrials.gov/ct2/show/NCT00387569
  • Marshall HS, Richmond PC, Nissen MD, et al. Safety and immunogenicity of a meningococcal B bivalent rLP2086 vaccine in healthy toddlers aged 18-36 months: a phase 1 randomized-controlled clinical trial. Pediatr Infect Dis J 2012;31(10):1061-8
  • Study Evaluating Safety, Tolerability, and Immunogenicity of Meningococcal B Vaccine in Healthy Infants. Available from: https://clinicaltrials.gov/ct2/show/NCT00798304
  • Available from: http://consurf.tau.ac.il/

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.