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2710. Novel Analytical Models for Pneumococcal Multiplex Opsonophagocytosis Assay Results from a Healthy Older Adult Population Vaccinated with PCV13

BACKGROUND: The multiplexed opsonophagocytosis assay (MOPA) measures killing of pneumococci by serum antibodies, and is the primary method for measuring pneumococcal antibodies in adults. However, pre-vaccine opsonic activity and vaccine response are highly variable among serotypes and individuals,...

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Autores principales: LaFon, David, Kim, Young, Nahm, Moon H
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6810961/
http://dx.doi.org/10.1093/ofid/ofz360.2387
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author LaFon, David
Kim, Young
Nahm, Moon H
author_facet LaFon, David
Kim, Young
Nahm, Moon H
author_sort LaFon, David
collection PubMed
description BACKGROUND: The multiplexed opsonophagocytosis assay (MOPA) measures killing of pneumococci by serum antibodies, and is the primary method for measuring pneumococcal antibodies in adults. However, pre-vaccine opsonic activity and vaccine response are highly variable among serotypes and individuals, and there are currently no criteria to define normal MOPA results. METHODS: We performed post-hoc analysis of data from n = 311 healthy, pneumococcal-vaccine naïve adults aged 55–74 who received 0.5 mL PCV13, and had MOPA performed for PCV13 serotypes (except serotype 3) at baseline, then on days 29 and 181 post-vaccine (Jackson et al. 2018, Vaccine). MOPA results (reported as opsonic index, or OI) were standardized using pneumococcal reference serum 007sp. Pairwise comparisons of proportions of undetectable baseline OI (≤ 4) between serotypes were performed using Pearson’s Chi-square. Immunogenicity (mean change in OI at day 29 post-PCV among samples with undetectable baseline OI) was compared between serotypes using one-way ANOVA. We then assigned a score based on cutoffs for pre-vaccine OI (cutoff 1, or C1) and fold-rise in OI at day 29 (cutoff 2, or C2) for each serotype, as shown in Figure 1. The sum of the scores for 12 serotypes was determined for each participant. We plotted the frequency distribution of total scores using different combinations of values for C1 and C2 to visually identify the optimal fit for the left-skewed distribution expected in a healthy population. RESULTS: Serotype 1 had the highest prevalence of undetectable OI at baseline (77.0%, P < 0.001), and serotype 19A had the lowest (8.8%, P < 0.001). Immunogenicity was highest for serotype 7F (mean change of 18354, P < 0.001 for all comparisons). For vaccine response analysis, C1 = 300 and C2 = 8 produced a left-skewed distribution (Figure 2). Using these cutoffs, the median total score was 7 and the 5th percentile score was −1. CONCLUSION: Criteria for normal MOPA results can be developed for single-timepoint data, or using a scoring system for vaccine response data that integrates pre-vaccine OI and fold-rise in OI. Additional studies in healthy and disease populations are needed to further optimize diagnostic criteria for discriminating normal vs. abnormal results. [Image: see text] [Image: see text] DISCLOSURES: All authors: No reported disclosures.
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spelling pubmed-68109612019-10-28 2710. Novel Analytical Models for Pneumococcal Multiplex Opsonophagocytosis Assay Results from a Healthy Older Adult Population Vaccinated with PCV13 LaFon, David Kim, Young Nahm, Moon H Open Forum Infect Dis Abstracts BACKGROUND: The multiplexed opsonophagocytosis assay (MOPA) measures killing of pneumococci by serum antibodies, and is the primary method for measuring pneumococcal antibodies in adults. However, pre-vaccine opsonic activity and vaccine response are highly variable among serotypes and individuals, and there are currently no criteria to define normal MOPA results. METHODS: We performed post-hoc analysis of data from n = 311 healthy, pneumococcal-vaccine naïve adults aged 55–74 who received 0.5 mL PCV13, and had MOPA performed for PCV13 serotypes (except serotype 3) at baseline, then on days 29 and 181 post-vaccine (Jackson et al. 2018, Vaccine). MOPA results (reported as opsonic index, or OI) were standardized using pneumococcal reference serum 007sp. Pairwise comparisons of proportions of undetectable baseline OI (≤ 4) between serotypes were performed using Pearson’s Chi-square. Immunogenicity (mean change in OI at day 29 post-PCV among samples with undetectable baseline OI) was compared between serotypes using one-way ANOVA. We then assigned a score based on cutoffs for pre-vaccine OI (cutoff 1, or C1) and fold-rise in OI at day 29 (cutoff 2, or C2) for each serotype, as shown in Figure 1. The sum of the scores for 12 serotypes was determined for each participant. We plotted the frequency distribution of total scores using different combinations of values for C1 and C2 to visually identify the optimal fit for the left-skewed distribution expected in a healthy population. RESULTS: Serotype 1 had the highest prevalence of undetectable OI at baseline (77.0%, P < 0.001), and serotype 19A had the lowest (8.8%, P < 0.001). Immunogenicity was highest for serotype 7F (mean change of 18354, P < 0.001 for all comparisons). For vaccine response analysis, C1 = 300 and C2 = 8 produced a left-skewed distribution (Figure 2). Using these cutoffs, the median total score was 7 and the 5th percentile score was −1. CONCLUSION: Criteria for normal MOPA results can be developed for single-timepoint data, or using a scoring system for vaccine response data that integrates pre-vaccine OI and fold-rise in OI. Additional studies in healthy and disease populations are needed to further optimize diagnostic criteria for discriminating normal vs. abnormal results. [Image: see text] [Image: see text] DISCLOSURES: All authors: No reported disclosures. Oxford University Press 2019-10-23 /pmc/articles/PMC6810961/ http://dx.doi.org/10.1093/ofid/ofz360.2387 Text en © The Author(s) 2019. Published by Oxford University Press on behalf of Infectious Diseases Society of America. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Abstracts
LaFon, David
Kim, Young
Nahm, Moon H
2710. Novel Analytical Models for Pneumococcal Multiplex Opsonophagocytosis Assay Results from a Healthy Older Adult Population Vaccinated with PCV13
title 2710. Novel Analytical Models for Pneumococcal Multiplex Opsonophagocytosis Assay Results from a Healthy Older Adult Population Vaccinated with PCV13
title_full 2710. Novel Analytical Models for Pneumococcal Multiplex Opsonophagocytosis Assay Results from a Healthy Older Adult Population Vaccinated with PCV13
title_fullStr 2710. Novel Analytical Models for Pneumococcal Multiplex Opsonophagocytosis Assay Results from a Healthy Older Adult Population Vaccinated with PCV13
title_full_unstemmed 2710. Novel Analytical Models for Pneumococcal Multiplex Opsonophagocytosis Assay Results from a Healthy Older Adult Population Vaccinated with PCV13
title_short 2710. Novel Analytical Models for Pneumococcal Multiplex Opsonophagocytosis Assay Results from a Healthy Older Adult Population Vaccinated with PCV13
title_sort 2710. novel analytical models for pneumococcal multiplex opsonophagocytosis assay results from a healthy older adult population vaccinated with pcv13
topic Abstracts
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6810961/
http://dx.doi.org/10.1093/ofid/ofz360.2387
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