scholarly journals Inadequacy of Colominic Acid as an Absorbent Intended To Facilitate Use of Complement-Preserved Baby Rabbit Serum in the Neisseria meningitidis Serogroup B Serum Bactericidal Antibody Assay

2007 ◽  
Vol 14 (5) ◽  
pp. 556-561 ◽  
Author(s):  
Jamie Findlow ◽  
Ann Holland ◽  
Diana Martin ◽  
Philipp Oster ◽  
Paul Balmer ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Neisseria Meningitidis ◽  
Rabbit Serum ◽  
Human Complement ◽  
Antibody Assay ◽  
Colominic Acid ◽  
Bactericidal Antibody ◽  
Serum Bactericidal Antibody Assay ◽  
Rabbit Complement ◽  
General Reduction

ABSTRACT The surrogate of protection against Neisseria meningitidis serogroup B (MenB) is the serum bactericidal antibody (SBA) assay, which measures the functional activity of antibody by using an exogenous complement source. Despite baby rabbit complement having been used in meningococcal serogroup A, C, Y, and W135 SBA assays, it is not recommended for use in the MenB SBA assay due to elevated SBA titers caused by low-avidity anti-MenB capsular antibody in test sera. Therefore, the possibility of absorbing anti-MenB capsular antibody from test sera to enable the use of baby rabbit complement in the MenB SBA assay was investigated by comparing the results with those gained using human complement. Colominic acid from Escherichia coli K1, which shares the same linkage residue as MenB polysaccharide, was used as an absorbent due to the commercial unavailability of purified MenB polysaccharide. Inclusion of soluble colominic acid as an absorbent with baby rabbit complement resulted in a general reduction in SBA titers compared with those obtained using baby rabbit complement alone. However, these were not comparable to human SBA titers for all samples. Further optimization and investigations demonstrated that for some samples, colominic acid reduced titers to less than those achieved with human complement, and for others, it was not possible to inhibit titers by using colominic acid. The results suggested that the use of colominic acid will not result in the ability to use baby rabbit complement in the MenB SBA assay, thus not alleviating the difficulties in procuring human complement. However, alternative absorbents, such as purified MenB polysaccharide, may warrant further evaluation.

scholarly journals Validation of Serological Correlate of Protection for Meningococcal C Conjugate Vaccine by Using Efficacy Estimates from Postlicensure Surveillance in England

2003 ◽  
Vol 10 (5) ◽  
pp. 780-786 ◽  
Author(s):  
Nick Andrews ◽  
Ray Borrow ◽  
Elizabeth Miller
Keyword(s):  
Age Groups ◽  
Immunologic Memory ◽  
Human Complement ◽  
Antibody Assay ◽  
Efficacy Data ◽  
Correlate Of Protection ◽  
Correlates Of Protection ◽  
Bactericidal Antibody ◽  
Serum Bactericidal Antibody Assay ◽  
Rabbit Complement

ABSTRACT Meningococcal C conjugate (MCC) vaccines were licensed on the basis of serological correlates of protection without efficacy data. The original correlate of protection was established by using a serum bactericidal antibody assay (SBA) with human complement (hSBA), with titers ≥4 predicting protection. However, the antibody data supporting licensure were largely generated by SBA with rabbit complement (rSBA), which gives higher titers than hSBA. While rSBA titers ≥128 reliably predict protection, as measured by hSBA, sera with rSBA titers in the range of 8 to 64 may not have hSBA titers ≥4. For rSBA titers in this equivocal range, a fourfold rise pre- to postvaccination with the MCC vaccine and/or a characteristic booster response to a polysaccharide challenge was proposed as a correlate of protection. To validate this proposed rSBA correlate, age-specific efficacy estimates for MCC vaccines obtained from postlicensure surveillance in England were compared with the efficacy predicted by the percentage of individuals in these age groups with rSBA titers above different cutoffs at 4 weeks and at 7 to 9 months after vaccination with the MCC vaccine. The average time since vaccination in the cohorts in whom efficacy was measured ranged from 8 to 10 months. The rSBA cutoff of ≥128 was shown to significantly underestimate efficacy, with rSBA cutoffs of ≥4 or ≥8 at 4 weeks postvaccination with the MCC vaccine being the most consistent with observed efficacy. When the levels obtained 7 to 9 months postvaccination with the MCC vaccine were used, all rSBA cutoffs significantly underestimated efficacy, suggesting that continuing protection is less dependent on the SBA level at the time of exposure but is more reliant on immunologic memory.

scholarly journals Immunogenicity and safety of a quadrivalent meningococcal tetanus toxoid-conjugate vaccine (MenACYW-TT) vs. a licensed quadrivalent meningococcal tetanus toxoid-conjugate vaccine in meningococcal vaccine-naïve and meningococcal C conjugate vaccine-primed toddlers: a phase III randomised study

2021 ◽  
Vol 149 ◽  
Author(s):  
D. van der Vliet ◽  
T. Vesikari ◽  
B. Sandner ◽  
F. Martinón-Torres ◽  
G. Muzsay ◽  
...  
Keyword(s):  
Conjugate Vaccine ◽  
Tetanus Toxoid ◽  
Phase Iii ◽  
Meningococcal Vaccine ◽  
Antibody Assay ◽  
Randomised Study ◽  
Antibody Titres ◽  
Bactericidal Antibody ◽  
Serum Bactericidal Antibody Assay ◽  
Quadrivalent Meningococcal Vaccine

Abstract Vaccination remains the best strategy to reduce invasive meningococcal disease. This study evaluated an investigational tetanus toxoid-conjugate quadrivalent meningococcal vaccine (MenACYW-TT) vs. a licensed tetanus toxoid-conjugate quadrivalent meningococcal vaccine (MCV4-TT) (NCT02955797). Healthy toddlers aged 12–23 months were included if they were either meningococcal vaccine-naïve or MenC conjugate (MCC) vaccine-primed (≥1 dose of MCC prior to 12 months of age). Vaccine-naïve participants were randomised 1:1 to either MenACYW-TT (n = 306) or MCV4-TT (n = 306). MCC-primed participants were randomised 2:1 to MenACYW-TT (n = 203) or MCV4-TT (n = 103). Antibody titres against each of the four meningococcal serogroups were measured by serum bactericidal antibody assay using the human complement. The co-primary objectives of this study were to demonstrate the non-inferiority of MenACYW-TT to MCV4-TT in terms of seroprotection (titres ≥1:8) at Day 30 in both vaccine-naïve and all participants (vaccine-naïve and MCC-primed groups pooled). The immune response for all four serogroups to MenACYW-TT was non-inferior to MCV4-TT in vaccine-naïve participants (seroprotection: range 83.6–99.3% and 81.4–91.6%, respectively) and all participants (seroprotection: range 83.6–99.3% and 81.4–98.0%, respectively). The safety profiles of both vaccines were comparable. MenACYW-TT was well-tolerated and demonstrated non-inferior immunogenicity when administered to MCC vaccine-primed and vaccine-naïve toddlers.

scholarly journals Monoclonal Antibodies Specific for Neisseria meningitidis Group B Polysaccharide and Their Peptide Mimotopes

2001 ◽  
Vol 69 (5) ◽  
pp. 3335-3342 ◽  
Author(s):  
J. S. Shin ◽  
J. S. Lin ◽  
P. W. Anderson ◽  
R. A. Insel ◽  
M. H. Nahm
Keyword(s):  
Amino Acids ◽  
Monoclonal Antibodies ◽  
Neisseria Meningitidis ◽  
The Other ◽  
Human Complement ◽  
E Coli ◽  
Peptide Mimotopes ◽  
Group B ◽  
K 12 ◽  
Rabbit Complement

ABSTRACT From five mice immunized with Escherichia coli K1 bacteria, we produced 12 immunoglobulin M hybridomas secreting monoclonal antibodies (MAbs) that bind to Neisseria meningitidis group B (NMGB). The 12 MAbs also bound the capsular polysaccharide (PS) of E. coli K1 [which, like NMGB, is α(2-8)-linked polysialic acid (PSA)] and bound to EV36, a nonpathogenic E. coli K-12 strain producing α(2-8) PSA. Except for HmenB5, which cross-reacted with N. meningitidis group C, none of the MAbs bound to N. meningitidis groups A, C, and Y. Of the 12 MAbs, 6 were autoantibodies as defined by binding to CHP-134, a neuroblastoma cell line expressing short-chain α(2-8) PSA; five of these MAbs killed NMGB in the presence of rabbit complement, and two also killed NMGB with human complement. The other six MAbs, however, were nonautoreactive; all killed NMGB with rabbit complement, and five killed NMGB with human complement. To obtain peptide mimotopes of NMGB PS, four of the nonautoreactive MAbs (HmenB2, HmenB3, HmenB13, and HmenB14) were used to screen two types of phage libraries, one with a linear peptide of 7 amino acids and the other with a circular peptide of 7 amino acids inserted between two linked cysteines. We obtained 86 phage clones that bound to the screening MAb in the absence but not in the presence of E. coli K1 PSA in solution. The clones contained 31 linear and 4 circular mimotopes expressing unique sequences. These mimotopes nonrandomly expressed amino acids and were different from previously described mimotopes for NMGB PS. The new mimotopes may be useful in producing a vaccine(s) capable of eliciting anti-NMGB antibodies not reactive with neuronal tissue.

scholarly journals Comparison of Phenotypically Indistinguishable but Geographically Distinct Neisseria meningitidis Group B Isolates in a Serum Bactericidal Antibody Assay

2007 ◽  
Vol 14 (11) ◽  
pp. 1451-1457 ◽  
Author(s):  
Jamie Findlow ◽  
Ann Holland ◽  
Nick Andrews ◽  
Vincent Weynants ◽  
Franklin Sotolongo ◽  
...  
Keyword(s):  
Neisseria Meningitidis ◽  
Capsular Polysaccharide ◽  
Membrane Vesicle ◽  
Geometric Mean ◽  
Future Studies ◽  
Standard Assay ◽  
Target Strain ◽  
Bactericidal Antibody ◽  
Group B ◽  
Serum Bactericidal Antibody Assay

ABSTRACT The “gold standard” assay for measuring serologic protection against Neisseria meningitidis group B (MenB) is the serum bactericidal antibody (SBA) assay. Of vital importance to the outcome of the SBA assay is the choice of the target strain(s), which is often chosen on the basis of phenotype or genotype. We therefore investigated the effect on the results produced by the SBA assay of using phenotypically indistinguishable but geographically distinct MenB isolates. Nine PorA P1.19,15 and 11 PorA P1.7-2,4 MenB isolates were incorporated into the SBA assay using human complement and were assayed against sera obtained either before or after outer membrane vesicle vaccination. Large differences in the results produced by the isolates in the SBA assay were demonstrated. These included differences as great as 5.8-fold in SBA geometric mean titers and in the proportions of subjects with SBA titers of ≥4. Ranges of as many as 9 SBA titers were achieved by individual sera across the panels of isolates. To determine the reasons for the differences observed, investigations into the expression of capsular polysaccharide, PorA, PorB, Opc, and lipooligosaccharide (LOS) and into LOS sialylation were completed. However, minor differences were found between strains, indicating similar expression and no antigen masking. These results have implications for the choice of MenB target strains for inclusion in future studies of MenB vaccines and highlight the requirement for standardization of target strains between laboratories.

scholarly journals Mucosal Vaccination against Serogroup B Meningococci: Induction of Bactericidal Antibodies and Cellular Immunity following Intranasal Immunization with NadA of Neisseria meningitidis and Mutants of Escherichia coli Heat-Labile Enterotoxin

2004 ◽  
Vol 72 (7) ◽  
pp. 4052-4060 ◽  
Author(s):  
Frances Bowe ◽  
Ed C. Lavelle ◽  
Edel A. McNeela ◽  
Christine Hale ◽  
Simon Clare ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Immune Responses ◽  
Neisseria Meningitidis ◽  
Cellular Responses ◽  
Mucosal Vaccine ◽  
Nasal Delivery ◽  
Th2 Cells ◽  
Intranasal Immunization ◽  
Heat Labile ◽  
Bactericidal Antibody

ABSTRACT Conjugated polysaccharide vaccines protect against serogroup C meningococci. However, this approach cannot be applied to serogroup B, which is still a major cause of meningitis. We evaluated the immunogenicity of three surface-exposed proteins from serogroup B Neisseria meningitidis (App, NhhA, and NadA) identified during whole-genome sequencing. Mice were immunized intranasally with individual proteins in the presence of wild-type Escherichia coli heat-labile enterotoxin (LTwt), LTR72, a partially inactivated mutant, or LTK63, a completely nontoxic mutant, as the adjuvant. Each of the meningococcal proteins induced significant cellular responses; NhhA and NadA induced strong antibody responses, but only NadA induced bactericidal antibody when administered intranasally with mucosal adjuvants. In addition, immunoglobulin A and bactericidal antibodies were detected in the respiratory tract following intranasal delivery of NadA. Analysis of antigen-specific cytokine production by T cells from immunized mice revealed that intranasal immunization with NadA alone failed to generate detectable cellular immune responses. In contrast, LTK63, LTR72, and LTwt significantly augmented NadA-specific gamma interferon, interleukin-4 (IL-4), IL-5, and IL-10 production by spleen and lymph node cells, suggesting that both Th1 and Th2 cells were induced in vivo. The strongest cellular responses and highest bactericidal antibody titers were generated with LTR72 as the adjuvant. These findings demonstrate that the quality and magnitude of the immune responses generated by mucosal vaccines are influenced by the antigen as well as the adjuvant and suggest that nasal delivery of NadA with mucosal adjuvants has considerable potential in the development of a mucosal vaccine against serogroup B meningococci.

#92: What Is the Optimal Management of Patients Immunosuppressed with the Anti-compliment Monoclonal Antibody, Eculizumab? A Case Report and Review

2021 ◽  
Vol 10 (Supplement_1) ◽  
pp. S12-S12
Author(s):  
I Tinoco ◽  
A Jarrell ◽  
L Correa ◽  
J Bissler ◽  
J DeVincenzo ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Renal Failure ◽  
Antibiotic Prophylaxis ◽  
Neisseria Meningitidis ◽  
Paroxysmal Nocturnal Hemoglobinuria ◽  
Neisseria Species ◽  
E Coli ◽  
Increased Risk ◽  
Prescribing Information ◽  
Rabbit Complement

Abstract Background Patients with deficiencies of terminal components of complement are at hundreds to thousands fold increased risk of severe and fatal Neisseria spp. infections compared with the general population. Eculizumab is a newly approved monoclonal antibody C5 complement inhibitor. It is indicated for the treatment of atypical hemolytic uremic syndrome (atypical HUS), myasthenia gravis, and paroxysmal nocturnal hemoglobinuria. Because of the complement-depleting effect of Eculizumab dosing (Soliris®, Alexion Pharmaceuticals, Munich, Germany), patients are immunosuppressed for specific infectious pathogens (including Neisseria species) against which protection partially relies on normal complement activity. Because Eculizumab treatment is associated with a dramatically increased risk of Neisseria species. infections, recommendations for Neisseria meningitidis vaccination and antibiotic prophylaxis are contained in Eculizumab prescribing information. However, the most appropriate prevention of infections after Eculizumab has yet to be determined. Methods Case report and literature review. Results A previously healthy 7-year-old male was diagnosed with atypical HUS which included renal failure progressing to dialysis, persistent thrombocytopenia, hemolytic anemia, and hemoglobinuria. Stool cultures and a stool multiplex PCR panel did not detect Shiga-like producing E. coli nor E. coli O157/H7. Eculizumab dosing was therefore planned and Infectious Diseases consultation was obtained for appropriate preventions. The FDA Prescribing Information recommends Neisseria meningitidis vaccination before starting Eculizumab or, if immediate Eculizumab is necessary, to use antibiotic prophylaxis until 2 weeks after vaccination. The accepted protective titer after meningococcal vaccination is population based and uses the serum bactericidal assay (SBA). An antibody titer of >1:4 (human compliment) or 1:8 (rabbit complement) is considered protective. However, this “gold standard” assay incorporates the use of exogenous human or rabbit complement. The protective SBA titers in subjects with terminal complement component deficiencies may not be properly assessed using these same SBA titer protective thresholds. Furthermore, serious meningococcal infections have occurred after appropriate vaccination in patients receiving chronic Eculizumab treatments (ie for paroxysmal nocturnal hemoglobinuria). Finally, SBA protective levels after single Neisseria meningitidis vaccination have not been achieved in majorities of patients with renal failure receiving dialysis and or transplant immunosuppression. Conclusions The current Eculizumab prescribing information recommendations for vaccination and antimicrobial prophylaxis may be inadequate to prevent serious Neisseria infections. Repeated Neisseria meningitidis vaccination and extended antibiotic prophylaxis may afford better protection in patients chronically dosed with Eculizumab.

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