A universal vaccine for serogroup B meningococcus.

Meningitis and sepsis caused by serogroup B meningococcus are two severe diseases that still cause significant mortality. To date there is no universal vaccine that prevents these diseases. In this work, five antigens discovered by reverse vaccinology were expressed in a form suitable for large-scale manufacturing and formulated with adjuvants suitable for human use. The vaccine adjuvanted by aluminum hydroxide induced bactericidal antibodies in mice against 78% of a panel of 85 meningococcal strains representative of the global population diversity. The strain coverage could be increased to 90% and above by the addition of CpG oligonucleotides or by using MF59 as adjuvant. The vaccine has the potential to conquer one of the most devastating diseases of childhood.

[1]  H. Tettelin,et al.  Identification of a Universal Group B Streptococcus Vaccine by Multiple Genome Screen , 2005, Science.

[2]  S. Funnell,et al.  Experimental disease models for the assessment of meningococcal vaccines. , 2005, Vaccine.

[3]  R. Rappuoli,et al.  Cell entry machines: a common theme in nature? , 2005, Nature Reviews Microbiology.

[4]  R. Rappuoli,et al.  The Region Comprising Amino Acids 100 to 255 of Neisseria meningitidis Lipoprotein GNA 1870 Elicits Bactericidal Antibodies , 2005, Infection and Immunity.

[5]  R. Rappuoli,et al.  Neisseria meningitidis NadA is a new invasin which promotes bacterial adhesion to and penetration into human epithelial cells , 2004, Molecular microbiology.

[6]  A. Pollard,et al.  Meningococcal polysaccharide-protein conjugate vaccines. , 2005, The Lancet. Infectious diseases.

[7]  R. Rappuoli,et al.  Putative vaccine antigens from Neisseria meningitidis recognized by serum antibodies of young children convalescing after meningococcal disease. , 2004, The Journal of infectious diseases.

[8]  Ying Zhang,et al.  Vaccine Potential of the Neisseria meningitidis 2086 Lipoprotein , 2004, Infection and Immunity.

[9]  R. Rappuoli,et al.  Antibody to genome-derived neisserial antigen 2132, a Neisseria meningitidis candidate vaccine, confers protection against bacteremia in the absence of complement-mediated bactericidal activity. , 2003, The Journal of infectious diseases.

[10]  Giuseppe Del Giudice,et al.  MF59-adjuvanted vaccines: increased immunogenicity with an optimal safety profile , 2003, Expert review of vaccines.

[11]  Jeannette Adu-Bobie,et al.  Vaccination against Neisseria meningitidis Using Three Variants of the Lipoprotein GNA1870 , 2003, The Journal of experimental medicine.

[12]  R. Rappuoli,et al.  NadA, a Novel Vaccine Candidate of Neisseria meningitidis , 2002, The Journal of experimental medicine.

[13]  N. Noah.  Surveillance of bacterial meningitis in Europe 1999/2000 , 2002 .

[14]  R. Rappuoli,et al.  A Novel Mimetic Antigen Eliciting Protective Antibody to Neisseria meningitidis1 , 2001, The Journal of Immunology.

[15]  S. Funnell,et al.  Recombinant Neisseria meningitidis Transferrin Binding Protein A Protects against Experimental Meningococcal Infection , 2001, Infection and Immunity.

[16]  J. Venter,et al.  Identification of vaccine candidates against serogroup B meningococcus by whole-genome sequencing. , 2000, Science.

[17]  S. Salzberg,et al.  Complete genome sequence of Neisseria meningitidis serogroup B strain MC58. , 2000, Science.

[18]  R. Weeratna,et al.  CpG DNA induces stronger immune responses with less toxicity than other adjuvants. , 2000, Vaccine.

[19]  R. Rappuoli.  Reverse vaccinology : Genomics , 2000 .

[20]  T. Popović,et al.  The changing epidemiology of meningococcal disease in the United States, 1992-1996. , 1999, The Journal of infectious diseases.

[21]  D. Granoff,et al.  Differences in Surface Expression of NspA amongNeisseria meningitidis Group B Strains , 1999, Infection and Immunity.

[22]  J. Tappero,et al.  Immunogenicity of 2 serogroup B outer-membrane protein meningococcal vaccines: a randomized controlled trial in Chile. , 1999, JAMA.

[23]  M. Achtman,et al.  Multilocus sequence typing: a portable approach to the identification of clones within populations of pathogenic microorganisms. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[24]  A. Krieg,et al.  CpG DNA is a potent enhancer of specific immunity in mice immunized with recombinant hepatitis B surface antigen. , 1998, Journal of immunology.

[25]  H. Hallander,et al.  Randomised controlled trial of two-component, three-component, and five-component acellular pertussis vaccines compared with whole-cell pertussis vaccine , 1997, The Lancet.

[26]  John E. Coligan,et al.  Current Protocols in Protein Science , 1996 .

[27]  R. Rappuoli,et al.  Development and phase 1 clinical testing of a conjugate vaccine against meningococcus A and C. , 1992, Vaccine.

[28]  D. Caugant,et al.  Multilocus genotypes determined by enzyme electrophoresis of Neisseria meningitidis isolated from patients with systemic disease and from healthy carriers. , 1986, Journal of general microbiology.

[29]  M. Artenstein,et al.  HUMAN IMMUNITY TO THE MENINGOCOCCUS IV. IMMUNOGENICITY OF GROUP A AND GROUP C MENINGOCOCCAL POLYSACCHARIDES IN HUMAN VOLUNTEERS , 1969 .

[30]  M. Artenstein,et al.  HUMAN IMMUNITY TO THE MENINGOCOCCUS I. THE ROLE OF HUMORAL ANTIBODIES , 1969 .

[31]  M. Artenstein,et al.  HUMAN IMMUNITY TO THE MENINGOCOCCUS : III. PREPARATION AND IMMUNOCHEMICAL PROPERTIES OF THE GROUP A, GROUP B, AND GROUP C MENINGOCOCCAL POLYSACCHARIDES , 1969 .