Porin A—Specific Antibody Avidity in Patients Who Are Convalescing from Meningococcal B Disease

Vermont, Clementien; Dijken, Harry H. van; Groot, Ronald de; Dobbelsteen, Germie P. J. M. van den

doi:10.1203/01.pdr.0000156372.13569.08

Cited by 4 publications

(5 citation statements)

References 22 publications

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“…This unparallel shape is more emphasized in samples with low AI (7), and as consequence the imprecision in AI evaluation is higher in serum samples with low avidity than with high-avidity antibodies. The reference points used here and shown in Table 1 are the same as those used in the literature: I) ODs corresponding to 0.2 or 0.1 are currently the choice for the single-point determination method (7); II) a serum dilution corresponding to OD 5 0.1 or 0.2 was also taken in the endpoint titration method (7,22); III) and a value that was 50% of the maximum OD, which corresponds to about 0.8 to 1.0, was also used (23,24). The AI calculated by the method of area is reliable because it takes into account the data of the whole ELISA titration curve, where the final numerical AI is the average of each point.…”

Section: Discussionmentioning

confidence: 99%

Improved method to calculate the antibody avidity index

Perciani

Peixoto

Dias

et al. 2007

Clinical Laboratory Analysis

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The methods currently used to determine the immunoglobulin avidity index (AI) require the choice of a reference point in the ELISA titration curve. Since both curves, with and without denaturating reagents, seldom run in parallel, the AI value becomes highly dependent on this reference. The new method for AI calculation presented here takes into account the whole data of the ELISA titration curve in which the final numerical AI is the average of each point.

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Section: Discussionmentioning

confidence: 99%

Improved method to calculate the antibody avidity index

Perciani

Peixoto

Dias

et al. 2007

Clinical Laboratory Analysis

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“…While de Kleijn et al (3) showed only a weak correlation between bactericidal levels and the levels of total IgG antibodies or isotype-specific levels (r ϭ 0.2 to 0.64; P Ͻ 0.01) in toddlers immunized with the RIVM hexavalent vaccine, Vermont et al (20) reported a strong correlation between SBAb and IgG1 levels (r ϭ 0.83; P Ͻ 0.0001) in a study involving toddlers immunized with a P1.7-2,4 monovalent recombinant OMV vaccine (MonoMen). However, in a study of children (average age, 6.3 years) who were convalescing from meningococcal disease with B:4:P1.7-2,4, Vermont et al (21) reported that although IgG1, followed by IgG3, dominated the IgG convalescent-phase serum response, serum bactericidal antibodies were not detected against the genetically modified strain of H44/76 expressing P1.7-2,4 PorA. The explanation for this is unclear.…”

Section: Vol 13 2006 Avidity and Igg Isotypes Measured In Infant Trmentioning

confidence: 99%

“…Low avidity has been reported in infants following infection with group B meningococci (15,21). When comparing the characteristics of immune responses induced by meningococcal infection in young children with those detected in children immunized with monovalent P1.7-2,4 OMV vaccine, Vermont et al (21) showed that the geometric mean AI in convalescent-phase sera (57%) was lower than the geometric mean AI of 73% induced by the monovalent vaccine (21). Those workers concluded that OMV vaccine may induce a better immune response than invasive meningococcal disease in young children.…”

Section: Vol 13 2006 Avidity and Igg Isotypes Measured In Infant Trmentioning

confidence: 99%

Understanding the Immune Responses to the Meningococcal Strain-Specific Vaccine MeNZB Measured in Studies of Infants

Ruijne

Lea

O’Hallahan

et al. 2006

Clin Vaccine Immunol

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Vaccine trials with infants enrolled between 6 and 10 weeks of age (young infants) and 6 and 8 months of age (older infants) provided an opportunity to evaluate immunoglobulin G (IgG) isotype distribution and avidity maturation as indicators of antibody function and immunologic memory. Following vaccination with a strain-specific outer membrane vaccine, MeNZB, pre-and postvaccination sera were used to determine IgG isotype responses and avidity indices (AI) in subsets of vaccinated subjects. Measurements of IgG isotypes involved 100 infants from each trial. AI were measured in 50 infants from the young infant trial who received a fourth vaccine dose and in 40 older infants from whom serum was collected 7 months after the primary vaccination course. IgG1 and IgG3 dominated the responses to the vaccine. A modest linear correlation (P < 0.001) occurred between serum bactericidal antibody (SBAb) titers and the total IgG or the IgG1 antibody units in older infants. The young infants showed a modest linear correlation between SBAb and total IgG (P ‫؍‬ 0.005) and a weak linear correlation between SBAb and IgG1 (P ‫؍‬ 0.003). Increased avidity with age was demonstrated in both groups. The AI in the young infants increased from 51.5% (95% confidence interval [CI], 47.7 to 54.7) postvaccination to 68.7% (95% CI, 65.5 to 71.9%) following the fourth dose of vaccine (P < 0.001). The mean avidity of the older infants increased significantly (P ‫؍‬ 0.00012) from 42.4% (95% CI, 39.1 to 45.3%) postvaccination to 50.4% (95% CI, 47.2 to 53.6%) 4 months later. A fourth dose of MeNZB is now being given to young infants at 10 months of age.

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“…Carbohydrates are known to produce a short-lived and comparatively weak immune response, as they elicit a T-cell-independent response. , Therefore, to enable T-cell-dependent B-cell activation and impart long-term immunity, glycans are frequently conjugated to a carrier protein. , Consequently, fluorinated disialoside 2 (DisAF) was covalently conjugated to CRM197, a commonly used and FDA-approved protein in glycoconjugate vaccines, and Porin A, a specific protein from N. meningitidis serogroup B . These carrier proteins were linked to the synthetic glycan using a p -nitrophenyl adipate ester as a coupling reagent, generating the semisynthetic glycoconjugates DisAF-CRM197, as a MenC vaccine lead, and DisAF-PorA as a bivalent vaccine against both serogroups (Figure A).…”

Section: Resultsmentioning

confidence: 99%

“…2f,19 Consequently, fluorinated disialoside 2 (DisAF) was covalently conjugated to CRM197, a commonly used and FDA-approved protein in glycoconjugate vaccines, 20 and Porin A, a specific protein from N. meningitidis serogroup B. 21 These carrier proteins were linked to the synthetic glycan using a pnitrophenyl adipate ester as a coupling reagent, generating the semisynthetic glycoconjugates DisAF-CRM197, as a MenC vaccine lead, and DisAF-PorA as a bivalent vaccine against both serogroups (Figure 3A).…”

Section: In Vivo Validation Of Vaccine Candidates In Micementioning

confidence: 99%

A Fluorinated Sialic Acid Vaccine Lead Against Meningitis B and C

Jordan,

Siebold,

Priegue

et al. 2024

J. Am. Chem. Soc.

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Inspired by the specificity of α-(2,9)-sialyl epitopes in bacterial capsular polysaccharides (CPS), a doubly fluorinated disaccharide has been validated as a vaccine lead against Neisseria meningitidis serogroups C and/or B. Emulating the importance of fluorine in drug discovery, this molecular editing approach serves a multitude of purposes, which range from controlling α-selective chemical sialylation to mitigating competing elimination. Conjugation of the disialoside with two carrier proteins (CRM197 and PorA) enabled a semisynthetic vaccine to be generated; this was then investigated in six groups of six mice. The individual levels of antibodies formed were compared and classified as highly glycan-specific and protective. All glycoconjugates induced a stable and long-term IgG response and binding to the native CPS epitope was achieved. The generated antibodies were protective against MenC and/or MenB; this was validated in vitro by SBA and OPKA assays. By merging the fluorinated glycan epitope of MenC with an outer cell membrane protein of MenB, a bivalent vaccine against both serogroups was created. It is envisaged that validation of this synthetic, fluorinated disialoside bioisostere as a potent antigen will open new therapeutic avenues.

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Porin A—Specific Antibody Avidity in Patients Who Are Convalescing from Meningococcal B Disease

Cited by 4 publications

References 22 publications

Improved method to calculate the antibody avidity index

Improved method to calculate the antibody avidity index

Understanding the Immune Responses to the Meningococcal Strain-Specific Vaccine MeNZB Measured in Studies of Infants

A Fluorinated Sialic Acid Vaccine Lead Against Meningitis B and C

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