Antibody responses to serogroup B meningococcal outer membrane antigens after vaccination and infection.

National Institute of Public Health, Oslo, Norway.
Journal of Clinical Microbiology (Impact Factor: 4.23). 09/1988; 26(8):1543-8.
Source: PubMed

ABSTRACT Antibody responses of adult volunteers given a vaccine containing meningococcal capsular polysaccharides (serogroups A, C, Y, and W-135) noncovalently complexed with serotype 2b:P1.2 and 15:P1.16 outer membrane proteins have been studied. Sera were analyzed by enzyme-linked immunosorbent assay methods for immunoglobulin G (IgG), IgM, and IgA antibodies and for bactericidal activities against the homologous strains. The vaccination was performed as a double-blind experiment with 47 volunteers, of whom 23 received the protein-polysaccharide vaccine and 24 received the control preparation containing the polysaccharides only. Ten additional persons volunteered for the protein-polysaccharide vaccine. Before vaccination, carriers of meningococci had significantly higher levels of specific IgG and IgA and also higher bactericidal activities than noncarriers. At 2 weeks postvaccination we found significant IgG and bactericidal antibody responses against both the 2b:P1.2 and 15:P1.16 strains in about 70% of the protein-polysaccharide vaccinees. The immune response induced by disease was compared with that induced by vaccination by analyzing paired sera from 13 survivors of serogroup B serotype 15 meningococcal disease. We found that the mean specific IgG level in acute-phase sera was lower than average in prevaccination sera from the vaccinees but similar to that of healthy noncarriers before vaccination. The convalescent-phase sera showed IgG responses similar to those of the vaccinees, but the IgM response to disease was significantly higher than after vaccination. The immune response to disease caused by serogroup B serotype 15 meningococci was found by enzyme-linked immunosorbent assay analysis to be about the same with outer-membrane antigens from a serotype 2b strain as it was with antigens from a serotype 15 strain.

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    Revista de Saúde Pública 08/1997; 31(4):402-416.
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    ABSTRACT: Novartis Vaccines has a long-standing research and development interest in the prevention of invasive meningococcal disease. From the initial licensure of the monovalent meningococcal C glycoconjugate vaccine, Menjugate(®), in response to the emergence of a virulent serogroup C ST-11 strain in the United Kingdom to the more recent development and licensure of a quadrivalent meningococcal ACWY glycoconjugate vaccine, Menveo(®), Novartis has a continuing commitment to the development of more effective tools for the control of meningococcal disease. Menveo is now licensed for use in adolescents and adults in over 50 countries and results from phase III studies have shown the vaccine to be well-tolerated and highly immunogenic in infants with vaccination beginning from 2 months of age. The 'holy grail' of meningococcal disease control is a broadly protective vaccine against serogroup B (MenB), preferably a vaccine that protects all age groups including infants. As the serogroup B capsule is poorly immunogenic, efforts over the past 40 years have focused on identifying conserved proteins expressed on the bacterial surface that elicit bactericidal antibodies. Novartis has approached this problem utilizing genomic tools to identify proteins meeting these criteria in a process now known as 'reverse vaccinology'[1]. This process has resulted in a novel multicomponent MenB vaccine (4CMenB) that consists of four major immunogenic components (three subcapsular MenB protein antigens plus outer membrane vesicles (OMVs) which themselves provide multiple subcapsular antigens, the immunodominant one being PorA). These all induce bactericidal antibodies against the antigens that are important in determining the survival, function, and virulence of the meningococci. Phase II studies of 4CMenB have been completed and have demonstrated that the vaccine is highly immunogenic against reference meningococcal strains selected to support licensure. Post-vaccination sera from clinical studies have also been tested against a diverse panel of serogroup B strains to support the development of the Meningococcal Antigen Typing System (MATS), a tool used to predict vaccine strain coverage [2] This overview is intended to give a broad summary of the key clinical data derived from the Menveo and 4CMenB clinical development programs.
    Vaccine 04/2012; 30 Suppl 2:B18-25. DOI:10.1016/j.vaccine.2012.01.062
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    ABSTRACT: We havedetermined theamountsofspecific anti-class 1outer membraneprotein antibodies inserafrom25 patients during thecourse ofsystemic meningococcal disease, using purified class 1protein asthesensitizing antigen inanenzyme-linked immunosorbent assay. Theclass 1protein wasobtained fromavariant ofstrain 44/76 (B:15:P1.7,16) lacking class 3andclass 4outermembraneproteins. Specific anti-class 1(serosubtype P1.7,16) outermembraneprotein immunoglobulin G (IgG)antibody levels increased significantly in12 patients (12of25;48%),regardless oftheserotype oftheinfecting strain, indicating thattheantibodies reacted inpartwithepitopes notdetermined bythemonoclonal antibodies usedforserotyping. Mostpatients hadlow levels ofanti-class 1IgGantibodies during theacute illness. Theantibody levels peaked during thesecond week ofdisease andreturned tonearbaseline levels inseracollected 6weeksto12monthsafter theonsetofthe disease. Themajority ofthespecific anti-class 1IgGantibodies boundtosurface-exposed epitopes onwhole bacteria andbelonged totheIgGlandIgG3subclasses. Anti-class 1IgAandIgMantibodies werenotdetected inanyofthepatient sera. Prior todisease, sevenpatients hadbeenimmunized withameningococcal outer membranevesicle vaccine developed fromstrain 44/76(P1.7,16). Noneofthesepatients wasinfected with meningococcal strains containing class 1protein homologous orpartly homologous tothatofthevaccine strain, indicating serosubtype-specific protection. Thehighest anti-class 1IgGantibody peaklevels wereseen inimmunized patients infected withstrains ofheterologous serotype, suggesting ananamnestic response. However, these patients werenotprotected frommeningococcal disease after immunization.

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