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2710. Novel Analytical Models for Pneumococcal Multiplex Opsonophagocytosis Assay Results from a Healthy Older Adult Population Vaccinated with PCV13
Author(s) -
David C. LaFon,
Young Ho Kim,
Moon H. Nahm
Publication year - 2019
Publication title -
open forum infectious diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.546
H-Index - 35
ISSN - 2328-8957
DOI - 10.1093/ofid/ofz360.2387
Subject(s) - serotype , medicine , pneumococcal conjugate vaccine , population , streptococcus pneumoniae , pneumococcal vaccine , immunogenicity , antibody , immunology , microbiology and biotechnology , biology , antibiotics , environmental health
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. Disclosures All authors: No reported disclosures.

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