Prediction of Pneumococcal Conjugate Vaccine Effectiveness against Invasive Pneumococcal Disease Using Opsonophagocytic Activity and Antibody Concentrations Determined by Enzyme-Linked Immunosorbent Assay with 22F Adsorption

Schuerman, Lode; Wysocki, Jacek; Tejedor, Juan Carlos; Knuf, Markus; Kim, K.-H.; Poolman, Jan

doi:10.1128/cvi.05313-11

Cited by 37 publications

(28 citation statements)

References 38 publications

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“…For 4, 14, and 19F, a threshold of $1 mg/mL is reported to give a better correspondence between the serological response rate and vaccine effectiveness. 20 In this study, for antibodies against 19A, 19F, 6B, and 14, a trough level $1 mg/mL was found in 80% to 98% of the patients. For antibodies against the other serotypes, only 1% to 53% of the patients achieved this threshold.…”

Section: Distribution Of Trough Pnpsab Levels In the Patient Populationmentioning

confidence: 46%

“…PnPsAbs in IVIG products have proved active in an opsonophagocytosis test thought to predict the functional potential of these antibodies. 11,20 We have used WHO 22F-ELISAs to measure trough and peak PnPsAbs specific to 16 serotypes. The reverse cumulative curves show a wide dispersion of levels and marked differences between serotypes (with 12F and 14 at the 2 extremes of the spectrum).…”

Section: Discussionmentioning

confidence: 99%

“…Trough levels of antibodies against serotypes 19A, 19F, 6B, and 14 reached the minimum protective level of 1 mg/ mL, found to correspond better with vaccine effectiveness against IPD due to serotypes 4, 14, and 19F in a conjugate vaccine trial conducted in the American Indian population and also found to protect normal children against pneumonia. 3,20,25,26 Only PnPsAbs against serotype 14 showed trough levels $1.3 mg/mL (93% of subjects), considered protective or adequate in all age groups after immunization with polysaccharide vaccine. Pieretti and Cunningham-Rundles 27 report that for antibodies against $7 of 14 serotypes, 11 of 20 immunodeficient patients had trough levels $1.3 mg/mL.…”

Section: Discussionmentioning

confidence: 99%

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Pneumococcal Antibody Levels in Children With PID Receiving Immunoglobulin

et al. 2014

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OBJECTIVES: Clinical data are lacking on optimal levels of specific antipneumococcal antibodies (PnPsAbs) in patients with primary immunodeficiency (PID) receiving intravenous immunoglobulin (IVIG) replacement. Objectives were to conduct a prospective multicenter study providing data on total immunoglobulin G (IgG) and peak/trough levels of PnPsAbs specifically targeting the 16 most prevalent pneumococcal serotypes in IVIG-treated children with PID; to compare trough PnPsAb levels with those measured in healthy adults and the IVIG product; and to evaluate PnPsAb protection correlates with thresholds based on World Health Organization. METHODS: Patients received 7 consecutive IVIG infusions. Total IgG and PnPsAb levels were determined on plasma samples obtained before and after infusion. RESULTS: Twenty-two children with PID were treated with IVIG (mean weekly dose: 0.10 g/kg). The mean trough and peak levels of total IgG were 7.77 and 13.93 g/L, respectively. Trough and peak geometric mean concentrations and distribution curves differed between serotypes and showed wide dispersion (0.17–7.96 µg/mL). In patients (89%–100%), antibodies against most serotypes reached trough levels ≥0.2 µg/mL, a threshold considered protective against invasive pneumococcal infection. For several serotypes, trough levels reached ≥1.0 to 1.3 µg/mL, the level found in adults. Trough geometric mean concentrations correlated well with the PnPsAb contents of the IVIG product. CONCLUSIONS: In IVIG-treated children with PID, protective PnPsAb levels for most pathogenic serotypes were obtained. A correlation was observed between PnPsAb levels in patients and in the IVIG product. This offers the potential to improve infection prevention by adapting the IVIG product and dose according to epidemiology.

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Section: Distribution Of Trough Pnpsab Levels In the Patient Populationmentioning

confidence: 46%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Pneumococcal Antibody Levels in Children With PID Receiving Immunoglobulin

et al. 2014

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“…While the measurement of antibody levels in serum using enzyme-linked immunosorbent assay (ELISA) methods can demonstrate the immunogenic potential of a vaccine, antibody levels do not always directly correlate with protection (11). This is the case for pneumococcal conjugate vaccines (PCVs), where measurement of functional antibody responses in opsonophagocytic killing assays (OPA) may correlate with clinical protection more closely than ELISA antibody levels (12)(13)(14).…”

mentioning

confidence: 99%

Development and Qualification of an Opsonophagocytic Killing Assay To Assess Immunogenicity of a Bioconjugated Escherichia coli Vaccine

Abbanat

Davies

Amsler

et al. 2017

Clin Vaccine Immunol

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The global burden of disease caused by extraintestinal pathogenic Escherichia coli (ExPEC) is increasing as the prevalence of multidrug-resistant strains rises. A multivalent ExPEC O-antigen bioconjugate vaccine could have a substantial impact in preventing bacteremia and urinary tract infections. Development of an ExPEC vaccine requires a readout to assess the functionality of antibodies. We developed an opsonophagocytic killing assay (OPA) for four ExPEC serotypes (serotypes O1A, O2, O6A, and O25B) based on methods established for pneumococcal conjugate vaccines. The performance of the assay was assessed with human serum by computing the precision, linearity, trueness, total error, working range, and specificity. Serotypes O1A and O6A met the acceptance criteria for precision (coefficient of variation for repeatability and intermediate precision, Յ50%), linearity (90% confidence interval of the slope of each strain, 0.80, 1.25), trueness (relative bias range, Ϫ30% to 30%), and total error (total error range, Ϫ65% to 183%) at five serum concentrations and serotypes O2 and O25B met the acceptance criteria at four concentrations (the lowest concentration for serotypes O2 and O25B did not meet the system suitability test of maximum killing of Ն85% of E. coli cells). All serotypes met the acceptance criteria for specificity (opsonization index value reductions of Յ20% for heterologous serum preadsorption and Ն70% for homologous serum preadsorption). The assay working range was defined on the basis of the lowest and highest concentrations at which the assay jointly fulfilled the target acceptance criteria for linearity, precision, and accuracy. An OPA suitable for multiple E. coli serotypes has been developed, qualified, and used to assess the immunogenicity of a 4-valent E. coli bioconjugate vaccine (ExPEC4V) administered to humans.KEYWORDS assay qualification, bacteremia, conjugate vaccine, Escherichia coli, ExPEC, invasive disease, opsonophagocytic killing assay B acteremia and septicemia, forms of invasive disease resulting from localized infections, are caused by various bacteria and bacterial toxins in the bloodstream (1) and are a significant cause of clinical morbidity and mortality. Septicemia is the 6th most frequent cause of hospitalization (1) and is the 10th leading cause of death in the United States (2). Associated economic costs are significant, and septicemia is the most expensive condition treated in U.S. hospitals, with 2009 aggregate expenditures approaching $15.4 billion, or approximately 4.3% of all hospital costs (1, 3). Extraintestinal pathogenic Escherichia coli (ExPEC) is the organism most frequently associated with sepsis in patients with a principal septicemia diagnosis (1), with E. coli septicemia case fatality rates ranging from 5% to 30% (4). Furthermore, ExPEC strains are the most

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“…This measure is considered to be predictive of vaccine protective potential against pneumococcal disease: OPA titers 8 correlated with 11Pn-PD efficacy against AOM 20 and were a better predictor of IPD protection with 7vCRM than the 22F-inhibition enzyme-linked immunosorbent assay (22F-ELISA). 21 Therefore, although there is no established correlate of PCV protection and standardization of OPA assays is ongoing, 22 transposability of efficacy results based on OPA immune responses is widely accepted. 23,24 In COMPAS, PHiD-CV showed efficacy of 26% against World Health Organization (WHO)-defined consolidated CAP and 22% against likely-bacterial CAP, 67% against vaccine serotype AOM, 65% against any IPD, and 100% against vaccine serotype IPD.…”

Section: Discussionmentioning

confidence: 99%

Immunogenicity and safety of the 10-valent pneumococcal nontypeableHaemophilus influenzaeprotein D conjugate vaccine (PHiD-CV) co-administered with DTPa vaccine in Japanese children: A randomized, controlled study

Iwata

Kawamura

Kuroki

et al. 2015

Human Vaccines & Immunotherapeutics

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This phase III, randomized, open-label, multicenter study (NCT01027845) conducted in Japan assessed the immunogenicity, safety, and reactogenicity of 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV, given intramuscularly) co-administered with diphtheria-tetanus-acellular pertussis vaccine (DTPa, given subcutaneously). Infants (N=360 ) were randomized (2:1) to receive either PHiD-CV and DTPa (PHiD-CV group) or DTPa alone (control group) as 3-dose primary vaccination (3–4–5 months of age) and booster vaccination (17–19 months of age). Immune responses were measured before and one month after primary/booster vaccination and adverse events (AEs) were recorded. Post-primary immune responses were non-inferior to those in pivotal/efficacy European or Latin American pneumococcal protein D-conjugate vaccine studies. For each PHiD-CV serotype, at least 92.6% of infants post-primary vaccination and at least 97.7% of children post-booster had pneumococcal antibody concentrations ≥0.2 μg/ml, and at least 95.4% post-primary and at least 98.1% post-booster had opsonophagocytic activity (OPA) titers ≥8 . Geometric mean antibody concentrations and OPA titers (except OPA titer for 6B) were higher post-booster than post-priming for each serotype. All PHiD-CV-vaccinated children had anti-protein D antibody concentrations ≥100 EL.U/ml one month post-primary/booster vaccination and all were seroprotected/seropositive against each DTPa antigen. Redness and irritability were the most common solicited AEs in both groups. Incidences of unsolicited AEs were comparable between groups. Serious AEs were reported for 47 children (28 in PHiD-CV group); none were assessed as vaccine-related. In conclusion, PHiD-CV induced robust immune responses and was well tolerated when co-administered with DTPa in a 3-dose priming plus booster regimen to Japanese children.

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Prediction of Pneumococcal Conjugate Vaccine Effectiveness against Invasive Pneumococcal Disease Using Opsonophagocytic Activity and Antibody Concentrations Determined by Enzyme-Linked Immunosorbent Assay with 22F Adsorption

Cited by 37 publications

References 38 publications

Pneumococcal Antibody Levels in Children With PID Receiving Immunoglobulin

Pneumococcal Antibody Levels in Children With PID Receiving Immunoglobulin

Development and Qualification of an Opsonophagocytic Killing Assay To Assess Immunogenicity of a Bioconjugated Escherichia coli Vaccine

Immunogenicity and safety of the 10-valent pneumococcal nontypeableHaemophilus influenzaeprotein D conjugate vaccine (PHiD-CV) co-administered with DTPa vaccine in Japanese children: A randomized, controlled study

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