Multistate population and whole genome sequence-based strain surveillance of invasive pneumococci recovered in the USA during 2017.

OBJECTIVES: We aimed to provide population-based and whole-genome sequence (WGS) -based characterization of invasive pneumococcal disease isolates collected from multistate surveillance in the USA during 2017. METHODS: We obtained short-read WGS from 2881 isolates with associated bioinformatics pipeline strain feature predictions. For quality control, capsular serotypes and antimicrobial MICs were also obtained conventionally from 442 isolates. Annotated WGS were provided (inclusive of serotypes, MICs, multilocus sequence types, pilus type(s)) from 2723 isolates. For 158 isolates with suboptimal WGS, antimicrobial MICs were obtained conventionally. RESULTS: There were 127 isolates from children <5 years of age and 2754 isolates from those ≥5 years old in 2017. One of 43 different serotypes was predicted for 2877 of the 2881 isolates. Serotypes in the 13-valent conjugate vaccine together with 6C (PCV13+6C) accounted for 816 (28.3%) isolates, with PCV13 serotype 3 being the most common serotype overall. Non-PCV13-6C- serotypes accounted for 2065 (71.7%) isolates, comprising 96 (75.6%) isolates from children < 5 years old and 1969 (61.4%) isolates from those aged ≥5 years. Of 36 different categories of recently emerged serotype-switch variants, three showed marked increases relative to 2015-2016 in that the number from 2017 surpassed the number from 2015-2016 combined. Two of these included antimicrobial-resistant serotype 11A and 35B serotype-switch variants of the ST156 clonal complex. CONCLUSIONS: PCV13+6C strains are still identified in 2017 but non-PCV13-type strains impose a considerable burden. This well-annotated year 2017 WGS/strain data set will prove useful for a broad variety of analyses and improved our understanding of invasive pneumococcal disease-causing strains in the post-PCV13 era.

Comparison of an opsonophagocytic assay and IgG ELISA to assess responses to pneumococcal polysaccharide and pneumococcal conjugate vaccines in children and young adults with sickle cell disease.

Children with sickle cell disease were immunized with either 2 doses of 7-valent pneumococcal conjugate vaccine followed by 1 dose of 23-valent pneumococcal polysaccharide vaccine or a single dose of 23-valent vaccine. Functional antibodies to 7 vaccine serotypes were measured by a flow cytometric opsonophagocytic assay (OPA) and compared with IgG anticapsular polysaccharide antibody concentrations measured by ELISA. Moderate correlations were found between OPA and ELISA antibody titers for all 7 serotypes (r values, 0.41-0.70; P<.001 for all serotypes). After immunization with 23-valent vaccine, geometric mean antibody titers by OPA were significantly higher in the combined schedule group for 5 of 7 vaccine serotypes but were significantly higher for only 2 of 7 serotypes as measured by ELISA. The ability of OPA to show a greater differential response to the 2 immunization schedules used in this study suggests that it may be useful in the evaluation of immunization regimens involving pneumococcal conjugate vaccines.

A flow cytometric opsonophagocytic assay for measurement of functional antibodies elicited after vaccination with the 23-valent pneumococcal polysaccharide vaccine.

Opsonophagocytosis is the primary mechanism for clearance of pneumococci from the host, and the measurement of opsonophagocytic antibodies appears to correlate with vaccine-induced protection. We developed a semiautomated flow cytometric opsonophagocytosis assay using HL-60 granulocytes as effector cells and nonviable 5, 6-carboxyfluorescein, succinimidyl ester-labeled Streptococcus pneumoniae (serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F) as bacterial targets. The flow cytometric opsonophagocytosis assay was highly reproducible (for 87% of repetitive assays the titers were within 1 dilution of the median titer) and serotype specific, with >/=97% inhibition of opsonophagocytic titer by addition of homologous serotype-specific polysaccharide. In general, opsonophagocytic titers were not significantly inhibited by the presence of either heterologous pneumococcal polysaccharide or penicillin in the serum. The flow cytometric assay could reproducibly measure functional antibody activity in prevaccination (n = 28) and postvaccination (n = 36) serum specimens from healthy adult volunteers vaccinated with the 23-valent pneumococcal polysaccharide vaccine. When compared with a standardized manual viable opsonophagocytic assay, a high correlation (r = 0.89; P