A Review of Research of Vaccine against Meningococcal Disease

  • Parviz Afrough Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran, Iran
  • Ava Behrouzi Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran, Iran.
  • Marjan Alimohammadi Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran, Iran
  • Seyed Davar Siadat Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran, Ira
Keywords: Meningitis, Neisseria meningitidis, Vaccines, Capsular polysaccharide


Background:     Meningococcal disease as a worldwide health problem causes approximately 1.2 million cases of bacterial meningitis, annually. Neisseria meningitidis a major cause of bacterial meningitis and serious diseases such as sepsis and bacteremia is fatal, and despite antibiotic treatments, the mortality rate of about 135 thousand cases has been reported. Meningococcal pathogen has been detected in nasopharynx of about 10-40% of the healthy people. There are several vaccines against six major groups of bacteria A, B, C, W135, X and Y. Although the bivalent (C-B), trivalent (A-C-Y) and quadrivalent (A-C-Y-W135) vaccines are used these days, there are yet significant rates of the disease in different geographical areas. Conclusion:   Although the polysaccharide capsule conjugate vaccine that have been developed against meningococcal serogroups A-C-Y and W135 are successful, but serogroup B because of the similarity with human polysialic glycoproteins is poorly immunogenic and to be cross-reactions. Thus, vaccines based on outer membrane vesicles have been designed for them


Yazdankhah, S.P. and D.A. Caugant, Neisseria meningitidis: an overview of the carriage state. Journal of medical microbiology, 2004. 53(9): p. 821-832.

Lewis, C. and S. Clarke, Identification of Neisseria meningitidis serogroups Y and W135 by said nucleotide sequence analysis. Journal of clinical microbiology, 2003. 41(6): p. 2697-2699.

Arreaza, L., L. de La Fuente, and J. Vázquez, Antibiotic Susceptibility Patterns of Neisseria meningitidis Isolates from Patients and Asymptomatic Carriers. Antimicrobial agents and chemotherapy, 2000. 44(6): p. 1705-1707.

Pizza, M. and R. Rappuoli, Neisseria meningitidis: pathogenesis and immunity. Current opinion in microbiology, 2015. 23: p. 68-72.

Sadarangani, M., A.J. Pollard, and S.D. Gray-Owen, Opa proteins, and CEACAMs: pathways of immune engagement for pathogenic Neisseria. FEMS microbiology reviews, 2011. 35(3): p. 498-514.

Bao, C., et al., Daidzein suppresses tumor necrosis factor-α induced migration and invasion by inhibiting hedgehog/Gli1 signaling in human breast cancer cells. Journal of agricultural and food chemistry, 2014. 62(17): p. 3759-3767.

Brown, D.R., et al., the Systematic functional analysis reveals that a set of seven genes is involved in fine-tuning of the multiple functions mediated by type IV pili in Neisseria meningitidis. Infection and immunity, 2010. 78(7): p. 3053-3063.

Siadat, S.D. and D. Norouzian, Meningococcal vaccines: past, present, and future perspective. J Infect Develop Count, 2007. 1(2): p. 129-46.

Morand, P.C., et al., Type IV pilus retraction in pathogenic Neisseria is regulated by the PilC proteins. The EMBO Journal, 2004. 23(9): p. 2009-2017.

Jafri, R.Z., et al., Global epidemiology of the invasive meningococcal disease. Population health metrics, 2013. 11(1): p. 1.

Apicella, M., S.B. Calderwood, and T.A. Kaplan SL, Epidemiology of Neisseria meningitidis infection. 2014.

Vyse, A., et al., Meningococcal disease in Asia: an under-recognized public health burden. Epidemiology and infection, 2011. 139(07): p. 967-985.

Sinclair, D., et al., The epidemiology of meningococcal disease in India. Tropical Medicine & International Health, 2010. 15(12): p. 1421-1435.

Jafari, H.S., B.A. Perkins, and J.D. Wenger, Control, and prevention of meningococcal disease: recommendations of the Advisory Committee on Immunization Practices (ACIP). Morbidity and Mortality Weekly Report: Recommendations and Reports, 1997: p. iv-10.

Bennett, J.E., R. Dolin, and M.J. Blaser, Principles and practice of infectious diseases. Vol. 1. 2014: Elsevier Health Sciences.

Robbins, J.B., et al., Enteric bacteria cross-reactive with Neisseria meningitidis groups A and C and Diplococcus pneumoniae types I and III. Infection and immunity, 1972. 6(5): p. 651-656.

Weidlich, L., et al., High prevalence of Neisseria meningitidis hypervirulent lineages and emergence of W135: P1. 5, 2: ST-11 clone in Southern Brazil. Journal of Infection, 2008. 57(4): p. 324-331.

Harrison, L.H., C.L. Trotter, and M.E. Ramsay, Global epidemiology of meningococcal disease. Vaccine, 2009. 27: p. B51-B63.

Pichichero, M., et al., the Comparative trial of the safety and immunogenicity of quadrivalent (A, C, Y, W-135) meningococcal polysaccharide-diphtheria conjugate vaccine versus quadrivalent polysaccharide vaccine in two-to ten-year-old children. The Pediatric infectious disease journal, 2005. 24(1): p. 57-62.

Tan, L.K., G.M. Carlone, and R. Borrow, Advances in the development of vaccines against Neisseria meningitidis. New England Journal of Medicine, 2010. 362(16): p. 1511-1520.

Girard, M.P., et al., A review of vaccine research and development: Meningococcal disease. Vaccine, 2006. 24(22): p. 4692-4700.

Shinefield, H.R., et al., Safety and immunogenicity of the heptavalent pneumococcal CRM197 conjugate vaccine in infants and toddlers. The Pediatric infectious disease journal, 1999. 18(9): p. 757-763.

Baxter, D., Active and passive immunity, vaccine types, excipients and licensing. Occupational Medicine, 2007. 57(8): p. 552-556.

Campbell, H., et al., Updated postlicensure surveillance of the meningococcal C conjugate vaccine in England and Wales: effectiveness, validation of serological correlates of protection, and modeling predictions of the duration of herd immunity. Clinical and Vaccine Immunology, 2010. 17(5): p. 840-847.

Perrett, K., et al., Antibody persistence after serogroup C meningococcal conjugate immunization of United Kingdom primary-school children in 1999–2000 and response to a booster: a phase 4 clinical trial. Clinical Infectious Diseases, 2010. 50(12): p. 1601-1610.

Miller, E., D. Salisbury, and M. Ramsay, Planning, registration, and implementation of an immunisation campaign against meningococcal serogroup C disease in the UK: a success story. Vaccine, 2001. 20: p. S58-S67.

Frasch, C., M.-P. Preziosi, and F.M. LaForce, Development of a group A meningococcal conjugate vaccine, MenAfriVacTM. Human Vaccines & Immunotherapeutics, 2012. 8(6): p. 715-724.

LaForce, F.M., et al., Epidemic meningitis due to Group A Neisseria meningitidis in the African meningitis belt: a persistent problem with an imminent solution. Vaccine, 2009. 27: p. B13-B19.

Knuf, M., et al., A dose-range study assessing immunogenicity and safety of one dose of a new candidate meningococcal serogroups A, C, W-135, Y tetanus toxoid conjugate (MenACWY-TT) vaccine administered in the second year of life and in young children. Vaccine, 2010. 28(3): p. 744-753.

Gill, C.J., et al., Persistence of immune responses after a single dose of Novartis meningococcal serogroup A, C, W-135 and Y CRM-197 conjugate vaccine (Menveo®) or Menactra® among healthy adolescents. Human vaccines, 2010. 6(11): p. 881-887.

Vesikari, T., et al., Tetravalent meningococcal serogroups A, C, W-135 and Y conjugate vaccine is well tolerated and immunogenic when co-administered with measles–mumps–rubella–varicella vaccine during the second year of life: an open, randomized controlled trial. Vaccine, 2011. 29(25): p. 4274-4284.

Pizza, M., et al., Identification of vaccine candidates against serogroup B meningococcus by whole-genome sequencing. Science, 2000. 287(5459): p. 1816-1820.

Pon, R.A., et al., N-Propionylated group B meningococcal polysaccharide mimics a unique bactericidal capsular epitope in group B Neisseria meningitidis. The Journal of experimental medicine, 1997. 185(11): p. 1929-1938.

Moe, G.R., A. Dave, and D.M. Granoff, Epitopes recognized by a nonautoreactive murine anti-N-propionyl meningococcal group B polysaccharide monoclonal antibody. Infection and immunity, 2005. 73(4): p. 2123-2128.

Schneider, M.C., et al., Interactions between Neisseria meningitidis and the complement system. Trends in microbiology, 2007. 15(5): p. 233-240.

Russo, T.A., et al., The K1 capsular polysaccharide from Acinetobacter baumannii is a potential therapeutic target via passive immunization. Infection and immunity, 2013. 81(3): p. 915-922.

Wu, Y., et al., Sustained high-titer antibody responses induced by conjugating a malarial vaccine candidate to outer-membrane protein complex. Proceedings of the National Academy of Sciences, 2006. 103(48): p. 18243-18248.

Feavers, I.M., Meningococcal vaccines and vaccine developments. Meningococcal vaccines: Methods and protocols, 2001: p. 1-22.

Mistretta, N., et al., Meningococcal vaccine based on lipooligosaccharide (LOS) originating from modified Neisseria meningitidis strains of immunotype L6. 2015, Google Patents.

Plested, J.S., et al., Conservation and accessibility of an inner core lipopolysaccharide epitope of Neisseria meningitidis. Infection and immunity, 1999. 67(10): p. 5417-5426.

Adl, S.M., et al., The new higher level classification of eukaryotes with emphasis on the taxonomy of protists. Journal of Eukaryotic Microbiology, 2005. 52(5): p. 399-451.

Mao, F., et al., Haloalkyl derivatives of reporter molecules used to analyze metabolic activity in cells. 1996, Google Patents.

Siadat, Seyed Davar,Norouzian, Dariush. Meningococcal vaccines: past, present, and future perspective, J Infect Develop,2007.1(2).p: 129-46

Holst, J., et al., Properties and clinical performance of vaccines containing outer membrane vesicles from Neisseria meningitidis. Vaccine, 2009. 27: p. B3-B12.

Salmani, A.S., et al., Outer membrane vesicle ofNeisseria meningitidis serogroup B as an adjuvant to induce specific antibody response against the lipopolysaccharide ofBrucella abortus S99. Annals of microbiology, 2009. 59(1): p. 145-149.

Di Cioccio, V., A.M. Colucci, and A. Saul, Purification of bacterial vesicles. 2014, Google Patents.

GVG, S., et al., Vaccine against group В Neisseria meningitidis: protection trial and mass vaccination results in Cuba. NPN Ann. 1991; 14: 195, 1991. 207.

Frasch, C.E., Vaccines for prevention of meningococcal disease. Clinical microbiology reviews, 1989. 2(Suppl): p. S134-S138.

Harrison, L.H., et al., The Global Meningococcal Initiative: recommendations for reducing the global burden of meningococcal disease. Vaccine, 2011. 29(18): p. 3363-3371.

Frasch, C.E., et al., Outer membrane protein vesicle vaccines for meningococcal disease. Meningococcal vaccines: methods and protocols, 2001: p. 81-107.

Hosking, J., et al., Immunogenicity, reactogenicity, and safety of a P1. 7b, 4 strain-specific serogroup B meningococcal vaccine given to preteens. Clinical and Vaccine Immunology, 2007. 14(11): p. 1393-1399.

Poolman, J., et al., Serotypes and subtypes of Neisseria meningitidis: results of an international study comparing sensitivities and specificities of monoclonal antibodies. Clinical and diagnostic laboratory immunology, 1995. 2(1): p. 69-72.

Kulp, D.W. and W.R. Schief, Advances in structure-based vaccine design. Current opinion in virology, 2013. 3(3): p. 322-331.

Martin, S., et al., Effect of sequence variation in meningococcal PorA outer membrane protein on the effectiveness of a hexavalent PorA outer membrane vesicle vaccine. Vaccine, 2000. 18(23): p. 2476-2481.

de Kleijn, E., et al., Serum bactericidal activity and isotype distribution of antibodies in toddlers and schoolchildren after vaccination with RIVM hexavalent PorA vesicle vaccine. Vaccine, 2001. 20(3): p. 352-358.

Vermont, C.L., et al., Cross-reactivity of antibodies against PorA after vaccination with a meningococcal B outer membrane vesicle vaccine. Infection and immunity, 2003. 71(4): p. 1650-1655.

Humphries, H.E., et al., Recombinant meningococcal PorA protein, expressed using a vector system with potential for human vaccination, induces a bactericidal immune response. Vaccine, 2004. 22(11): p. 1564-1569.

Al‐Bader, T., et al., Activation of human dendritic cells by the PorA protein of Neisseria meningitidis. Cellular microbiology, 2004. 6(7): p. 651-662.

Madico, G., et al., The meningococcal vaccine candidate GNA1870 binds the complement regulatory protein factor H and enhances serum resistance. The Journal of Immunology, 2006. 177(1): p. 501-510.

Zhu, D., et al., Intranasal immunization of mice with recombinant lipidated P2086 protein reduces nasal colonization of group B Neisseria meningitidis. Vaccine, 2006. 24(26): p. 5420-5425.

Caesar, N.M., K.A. Myers, and X. Fan, Neisseria meningitidis serogroup B vaccine development. Microbial pathogenesis, 2013. 57: p. 33-40.

Kotelnikova, E.A., V.J. Makeev, and M.S. Gelfand, Evolution of transcription factor DNA binding sites. Gene, 2005. 347(2): p. 255-263.

Vesikari, T., et al., European society for paediatric infectious diseases/European society for paediatric gastroenterology, hepatology, and nutrition evidence-based recommendations for rotavirus vaccination in Europe. Journal of pediatric gastroenterology and nutrition, 2008. 46: p. S38-S48.

Jódar, L., et al., Development of vaccines against meningococcal disease. The Lancet, 2002. 359(9316): p. 1499-1508.

Rezaei, N., et al., Serum bactericidal antibody responses to meningococcal polysaccharide vaccination as a basis for clinical classification of common variable immunodeficiency. Clinical and vaccine Immunology, 2008. 15(4): p. 607-611.

Nürnberger, T. and F. Brunner, Innate immunity in plants and animals: emerging parallels between the recognition of general elicitors and pathogen-associated molecular patterns. Current opinion in plant biology, 2002. 5(4): p. 318-324.

West, A.P., A.A. Koblansky, and S. Ghosh, Recognition and signaling by toll-like receptors. Annu. Rev. Cell Dev. Biol., 2006. 22: p. 409-437.

Feuillet, V., et al., Involvement of Toll-like receptor 5 in the recognition of flagellated bacteria. Proceedings of the National Academy of Sciences, 2006. 103(33): p. 12487-12492.

Heumann, D. and T. Roger, Initial responses to endotoxins and Gram-negative bacteria. Clinica Chimica Acta, 2002. 323(1): p. 59-72.

Mackenzie, J.E., Immunomodulatory properties of meningococcal outer membrane vesicles. 2006, University of London.

Allen, J.S., Dendritic cells and the immune response to Neisseria meningitis. 2004, University of London.

Burke, J.M., et al., Neisseria meningitidis PorB, a TLR2 ligand, induces an antigen-specific eosinophil recall response: potential adjuvant for helminth vaccines? The Journal of Immunology, 2007. 179(5): p. 3222-3230.

Singleton, T.E., P. Massari, and L.M. Wetzler, Neisserial porin-induced dendritic cell activation is MyD88 and TLR2 dependent. The Journal of Immunology, 2005. 174(6): p. 3545-3550.

Wetzler, L.M., Innate immune function of the neisserial porins and the relationship to vaccine adjuvant activity. Future microbiology, 2010. 5(5): p. 749-758.

Zughaier, S.M., Neisseria meningitidis capsular polysaccharides induce inflammatory responses via TLR2 and TLR4-MD-2. Journal of leukocyte biology, 2011. 89(3): p. 469-480.

Meyers, L.A., et al., Epidemiology, hypermutation, within–host evolution and the virulence of Neisseria meningitidis. Proceedings of the Royal Society of London B: Biological Sciences, 2003. 270(1525): p. 1667-1677.

Yi, H., et al., Pattern recognition scavenger receptor SRA/CD204 down-regulates Toll-like receptor 4 signaling–dependent CD8 T-cell activation. Blood, 2009. 113(23): p. 5819-5828.

Schmitt, C., A. Villwock, and O. Kurzai, Recognition of meningococcal molecular patterns by innate immune receptors. International Journal of Medical Microbiology, 2009. 299(1): p. 9-20.

Guo, C., et al., Absence of scavenger receptor A promotes dendritic cell-mediated cross-presentation of cell-associated antigen and antitumor immune response. Immunology and cell biology, 2012. 90(1): p. 101-108.

Peiser, L., S. Mukhopadhyay, and S. Gordon, Scavenger receptors in innate immunity. Current opinion in immunology, 2002. 14(1): p. 123-128.

Keane, M.P., E. Kelly, and R.M. Strieter, Chemokines and Cytokines in ARDS. Acute Respiratory Distress Syndrome, 2016. 233: p. 432.

Criss, A.K. and H.S. Seifert, A bacterial siren song: intimate interactions between Neisseria and Neutrophiles. Nature Reviews Microbiology, 2012. 10(3): p. 178-190.

Tettelin, H., et al., Complete genome sequence of Neisseria meningitidis serogroup B strain MC58. Science, 2000. 287(5459): p. 1809-1815.

Gordon, S., Pattern recognition receptors: doubling up for the innate immune response. Cell, 2002. 111(7): p. 927-930.

Mesa, C., et al., Very small size proteoliposomes derived from Neisseria meningitidis: an effective adjuvant for Th1 induction and dendritic cell activation. Vaccine, 2004. 22(23): p. 3045-3052.

Heine, H. and A. Ulmer, Recognition of bacterial products by toll-like receptors, in Mechanisms of Epithelial Defense. 2005, Karger Publishers. p. 99-119.

Massari, P., et al., Improved purification of native meningococcal porin PorB and studies on its structure/function. Protein expression and purification, 2005. 44(2): p. 136-146.

Lee, H.S., et al., Neisserial outer membrane vesicles bind the coinhibitory receptor carcinoembryonic antigen-related cellular adhesion molecule 1 and suppress CD4+ T lymphocyte function. Infection and immunity, 2007. 75(9): p. 4449-4455.

Scapini, P., et al., The neutrophil as a cellular source of chemokines. Immunological reviews, 2000. 177(1): p. 195-203.

Roeder, A., et al., Toll-like receptors and innate antifungal responses. Trends in microbiology, 2004. 12(1): p. 44-49.

Frosch, M. and M.C. Maiden, Handbook of meningococcal disease. 2006: Wiley Online Library.

Siadat, Seyed Davar, et al., Outer membrane vesicle of Neisseria meningitidis serogroup B as an adjuvant in immunization of rabbit against Neisseria meningitidis serogroup A, African J of Microbiology Research, 2011.19(5): p. 309-95.

How to Cite
Afrough P, Behrouzi A, Alimohammadi M, Siadat SD. A Review of Research of Vaccine against Meningococcal Disease. jmb. 7(3-4):49-.
Review Articles