Expression of concern: “Could the multicomponent meningococcal serogroup B vaccine (4CMenB) control Neisseria meningitidis capsular group X outbreaks in Africa?” and “Bactericidal antibody against a representative epidemiological meningococcal serogroup”

Vaccine ◽  
2020 ◽  
Vol 38 (35) ◽  
pp. 5577
Author(s):  
Gregory A. Poland
Keyword(s):  
Neisseria Meningitidis ◽  
Bactericidal Antibody

scholarly journals Comparison and Correlation of Neisseria meningitidis Serogroup B Immunologic Assay Results and Human Antibody Responses following Three Doses of the Norwegian Meningococcal Outer Membrane Vesicle Vaccine MenBvac

2006 ◽  
Vol 74 (8) ◽  
pp. 4557-4565 ◽  
Author(s):  
Jamie Findlow ◽  
Stephen Taylor ◽  
Audun Aase ◽  
Rachel Horton ◽  
Robert Heyderman ◽  
...  
Keyword(s):  
Neisseria Meningitidis ◽  
Outer Membrane ◽  
Membrane Vesicle ◽  
Enzyme Linked Immunosorbent Assay ◽  
Human Antibody ◽  
Outer Membrane Vesicle ◽  
Phagocytic Cells ◽  
Bactericidal Antibody ◽  
Antibody Elisa ◽  
Immunologic Assays

ABSTRACT The prediction of efficacy of Neisseria meningitidis serogroup B (MenB) vaccines is currently hindered due to the lack of an appropriate correlate of protection. For outer membrane vesicle (OMV) vaccines, immunogenicity has primarily been determined by the serum bactericidal antibody (SBA) assay and OMV enzyme-linked immunosorbent assay (ELISA). However, the opsonophagocytic assay (OPA), surface labeling assay, whole blood assay (WBA), and salivary antibody ELISA have been developed although correlation with protection is presently undetermined. Therefore, the aim of the study was to investigate further the usefulness of, and relationships between, MenB immunologic assays. A phase II trial of the OMV vaccine, MenBvac, with proven efficacy was initiated to compare immunologic assays incorporating the vaccine and six heterologous strains. Correlations were achieved between the SBA assay, OMV ELISA, and OPA using human polymorphonuclear leukocytes and human complement but not between an OPA using HL60 phagocytic cells and baby rabbit complement. Correlations between the surface labeling assay, the SBA assay, and the OMV ELISA were promising, although target strain dependent. Correlations between the salivary antibody ELISA and other assays were poor. Correlations to the WBA were prevented since many samples had results greater than the range of the assay. The study confirmed the immunogenicity and benefit of a third dose of MenBvac against the homologous vaccine strain using a variety of immunologic assays. These results emphasize the need for standardized methodologies that would allow a more robust comparison of assays between laboratories and promote their further evaluation as correlates of protection against MenB disease.

scholarly journals Different Long-Term Duration of Seroprotection against Neisseria meningitidis in Adolescents and Middle-Aged Adults after a Single Meningococcal ACWY Conjugate Vaccination in The Netherlands

Vaccines ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 624
Author(s):  
Milou Ohm ◽  
Debbie M. van Rooijen ◽  
Axel A. Bonačić Marinović ◽  
Mariëtte B. van Ravenhorst ◽  
Marieke van der Heiden ◽  
...  
Keyword(s):  
Single Dose ◽  
The Netherlands ◽  
Neisseria Meningitidis ◽  
Middle Aged ◽  
Bactericidal Antibody ◽  
Exponential Decay Model ◽  
Protective Antibodies ◽  
Duration Of Protection ◽  
Middle Aged Adults ◽  
Conjugate Vaccination

Neisseria meningitidis is often asymptomatically carried in the nasopharynx but may cause invasive meningococcal disease, leading to morbidity and mortality. Meningococcal conjugate vaccinations induce functional protective antibodies against capsular antigens, but seroprotection wanes over time. We measured functional antibody titers five years after administration of a single dose of the meningococcal ACWY-polysaccharide-specific tetanus toxoid-conjugated (MenACWY-TT) vaccine in adolescents and middle-aged adults in the Netherlands, using the serum bactericidal antibody with baby rabbit complement (rSBA) assay. Protection was defined as rSBA titer ≥8. The meningococcal ACWY-specific serum IgG concentrations were measured with a multiplex immunoassay. Duration of protection was estimated by a bi-exponential decay model. Sufficient protection for MenC, MenW, and MenY was achieved in 94–96% of the adolescents five years postvaccination, but, in middle-aged adults, only in 32% for MenC, 65% for MenW and 71% for MenY. Median duration of protection for MenCWY was 4, 14, and 21 years, respectively, in middle-aged adults, while, in adolescents, it was 32, 98, and 33 years. Our findings suggest that adolescents, primed in early childhood with MenC conjugate vaccination, remain sufficiently protected after a single dose of MenACWY-TT vaccine. Middle-aged adults without priming vaccination show fast waning of antibodies, particularly MenC, for which protection is lost after four years.

scholarly journals Sequential Immunization with Vesicles Prepared from Heterologous Neisseria meningitidis Strains Elicits Broadly Protective Serum Antibodies to Group B Strains

2002 ◽  
Vol 70 (11) ◽  
pp. 6021-6031 ◽  
Author(s):  
Gregory R. Moe ◽  
Patricia Zuno-Mitchell ◽  
Samantha N. Hammond ◽  
Dan M. Granoff
Keyword(s):  
Neisseria Meningitidis ◽  
Capsular Polysaccharide ◽  
Protein A ◽  
Surface Protein ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Novel Approach ◽  
Bactericidal Antibody ◽  
Porin Proteins ◽  
Group B

ABSTRACT The capsular polysaccharide of Neisseria meningitidis group B is an autoantigen, whereas noncapsular antigens are highly variable. These factors present formidable challenges for development of a broadly protective and safe group B vaccine. Mice and guinea pigs were sequentially immunized with three doses of micovesicles or outer membrane vesicles prepared from three meningococcal strains that were each antigenically heterologous with respect to the two major porin proteins, PorA and PorB, and the group capsular polysaccharide. The resulting antisera conferred passive protection against meningococcal group B bacteremia in infant rats and elicited complement-mediated bactericidal activity against genetically diverse group B strains that were either homologous or heterologous with respect to PorA of the strains used to prepare the vaccine. By using knockout strains, a portion of the bactericidal antibody was directed against the highly conserved protein, neisserial surface protein A (NspA). Further, an anti-NspA monoclonal antibody elicited by the sequential immunization was highly bactericidal against strains that were previously shown to be resistant to bacteriolysis by anti-NspA antibodies produced by immunization with recombinant NspA. Sequential immunization with heterologous vesicle preparations offers a novel approach to eliciting broadly protective immunity against N. meningitidis strains. An NspA-based vaccine prepared from protein expressed by Neisseria also may be more effective than the corresponding recombinant protein made in Escherichia coli.

scholarly journals Analysis of the Bactericidal Response to an Experimental Neisseria meningitidis Vesicle Vaccine

2012 ◽  
Vol 19 (5) ◽  
pp. 659-665 ◽  
Author(s):  
Elizabeth E. Moran ◽  
Robert Burden ◽  
Joseph E. Labrie ◽  
Zhiyun Wen ◽  
Xin-Min Wang ◽  
...  
Keyword(s):  
Antibody Response ◽  
Neisseria Meningitidis ◽  
Outer Membrane ◽  
Bactericidal Activity ◽  
Membrane Vesicle ◽  
Small Sample ◽  
Outer Membrane Vesicle ◽  
Content Type ◽  
Bactericidal Antibody ◽  
Membrane Antigens

ABSTRACTRabbit immunogenicity studies on an experimental trivalent native outer membrane vesicle vaccine derived from three serogroup B strains were conducted to evaluate the effectiveness of this vaccine at inducing an antibody response with serum bactericidal activity against meningococcal strains of other serogroups in addition to serogroup B strains. The results showed that the vaccine was capable of inducing an effective broad-based bactericidal antibody response in rabbits against a small sample ofNeisseria meningitidisstrains of serogroups C, W135, and X and, to a lesser extent, serogroups A and Y. Analysis of antibody specificity using a bactericidal depletion assay revealed that antibodies to lipooligosaccharide (LOS), PorA, and NadA induced in rabbits by the experimental trivalent outer membrane vesicle vaccine were responsible for most of the bactericidal activity against strains of the otherN. meningitidisserogroups. In the case of serogroup AN. meningitidisstrains, the outer membrane antigen NadA was primarily responsible for protection. The outer membrane antigens fHbp and OpcA were also effective in removing some bactericidal activity from the sera.

Structural basis for selective cross-reactivity in a bactericidal antibody against inner core lipooligosaccharide from Neisseria meningitidis†,‡

Glycobiology ◽  
2014 ◽  
Vol 24 (5) ◽  
pp. 442-449 ◽  
Author(s):  
Matthew J Parker ◽  
Kathryn Gomery ◽  
Gabrielle Richard ◽  
C Roger MacKenzie ◽  
Andrew D Cox ◽  
...  
Keyword(s):  
Neisseria Meningitidis ◽  
Inner Core ◽  
Cross Reactivity ◽  
Structural Basis ◽  
Bactericidal Antibody

Seroprevalence of bactericidal antibody against Neisseria meningitidis serogroup C in pre-vaccinal era: The Italian epidemiological scenario

Vaccine ◽  
2009 ◽  
Vol 27 (25-26) ◽  
pp. 3435-3438 ◽  
Author(s):  
R. Gasparini ◽  
R. Rizzetto ◽  
T. Sasso ◽  
E. Rizzitelli ◽  
P. Manfredi ◽  
...  
Keyword(s):  
Neisseria Meningitidis ◽  
Bactericidal Antibody

Bactericidal Antibody after Colonization with Neisseria meningitidis

1973 ◽  
Vol 127 (1) ◽  
pp. 56-62 ◽  
Author(s):  
L. B. Reller ◽  
R. R. MacGregor ◽  
H. N. Beaty
Keyword(s):  
Neisseria Meningitidis ◽  
Bactericidal Antibody

scholarly journals Humoral Immune Responses to Neisseria meningitidis in Children

1999 ◽  
Vol 67 (5) ◽  
pp. 2441-2451 ◽  
Author(s):  
Andrew J. Pollard ◽  
Rachel Galassini ◽  
Eileene M. Rouppe van der Voort ◽  
Robert Booy ◽  
Paul Langford ◽  
...  
Keyword(s):  
Immune Responses ◽  
Neisseria Meningitidis ◽  
Bactericidal Activity ◽  
Enzyme Linked Immunosorbent Assay ◽  
Older Children ◽  
Recent Infection ◽  
Humoral Immune ◽  
Serum Bactericidal Activity ◽  
Humoral Immune Responses ◽  
Bactericidal Antibody

ABSTRACT An understanding of the nature of immunity to serogroup B meningococci in childhood is necessary in order to establish the reasons for poor responses to candidate vaccines in infancy. We sought to examine the nature of humoral immune responses following infection in relation to age. Serum bactericidal activity was poor in children under 12 months of age despite recent infection with Neisseria meningitidis. The highest levels of bactericidal activity were seen in children over 10 years of age. However, infants produced levels of total immunoglobulin G (IgG) and IgG subclass antibodies similar to those in older children in a meningococcal enzyme-linked immunosorbent assay. Most antibody was of the IgG1 and IgG3 subclasses. This striking age dependency of bactericidal antibody response following infection is not apparently due to failure of class switching in infants but might be due to qualitative differences in antibody specificity or affinity.

scholarly journals Seroprevalence of Antibody-Mediated, Complement-Dependent Opsonophagocytic Activity against Neisseria meningitidis Serogroup B in England

2015 ◽  
Vol 22 (5) ◽  
pp. 503-509 ◽  
Author(s):  
Holly E. Humphries ◽  
Charlotte Brookes ◽  
Lauren Allen ◽  
Eeva Kuisma ◽  
Andrew Gorringe ◽  
...  
Keyword(s):  
Neisseria Meningitidis ◽  
Bactericidal Activity ◽  
Disease Incidence ◽  
Age Group ◽  
Serum Samples ◽  
Complex Situation ◽  
Content Type ◽  
Serum Bactericidal Activity ◽  
Bactericidal Antibody ◽  
Antibody Titers

ABSTRACTThe correlate of protection for the licensure of meningococcal vaccines is serum bactericidal activity. However, evidence indicates that a complex situation and other mechanisms, such as antibody-mediated, complement-dependent opsonophagocytosis (OP), may play a role in protection and should be investigated in order to understand immunity to this disease. In this study, a high-throughput flow cytometric opsonophagocytic assay (OPA) was optimized. The assay measures the presence of killed fluorescently labeledNeisseria meningitidiswithin human granulocytes (differentiated HL60 cells) by flow cytometry, using IgG-depleted pooled human plasma as an exogenous source of complement. This method was found to be reliable and correlated with the results of an opsonophagocytic killing assay. The OPA was used to measure OP activity in 1,878 serum samples from individuals ranging from 0 to 99 years of age againstN. meningitidisstrain NZ98/254 (B:4:P1.7-2,4). The levels of OP activity in individual serum samples varied greatly. OP activity showed an initial peak in the 6- to 12-month age group corresponding to a peak in disease incidence. The OP activity dropped in childhood until the late teenage years, although there was still a higher percentage of individuals with OP activity than with protective bactericidal antibody titers. OP activity reached a peak in the 30- to 39-year age group and then declined. This later peak in OP activity did not coincide with the young adults in whom peak serum bactericidal activity and disease incidence occurred. The demonstration of OP activity when disease incidence is low and when protective bactericidal antibody titers are not detected may indicate a role for OP in protection from meningococcal disease in these age groups.

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