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      An adult case of invasive pneumococcal disease due to serotype 12F-specific polysaccharide antibody failure following a 23-valent polysaccharide vaccination

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          ABSTRACT

          A 68-year-old Japanese man was admitted to our hospital for an acute febrile illness with shivering and impaired consciousness. He was a previous smoker and had a history of chronic obstructive pulmonary disease, for which he inhaled steroid with a long-acting bronchodilator. He had received a 23-valent pneumococcal polysaccharide vaccination 2 years previously. He was intubated and placed on a ventilator in intensive care unit because of acute respiratory failure and hypercapnia. Streptococcus pneumoniae was grown from his blood, sputum, and urine cultures, and he was diagnosed with invasive pneumococcal disease with acute renal failure. He was treated with intravenous beta-lactam and macrolide with continuous hemodiafiltration and was discharged 3 months later. The pneumococcus was identified as serotype 12F, and his serotype-specific IgG and opsonophagocytic index against serotype 12F indicating a lack of protection from IPD among PPV23 serotypes. This case highlights that some individuals may have a serotype-specific polysaccharide antibody failure that makes them susceptible to serotype 12F invasive pneumococcal disease. This case also illustrates the need for serotype-specific IgG and opsonophagocytic index titre cut-offs for each specific pneumococcal serotype in available vaccines to understand the vaccination protection for individual patients better.

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          Most cited references12

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          Development and validation of a fourfold multiplexed opsonization assay (MOPA4) for pneumococcal antibodies.

          Opsonophagocytic killing assays (OPAs) are essential for developing and improving pneumococcal vaccines. There is a need for a high-throughput, reliable, standardized, and fully characterized OPA for pneumococcal antibodies. To meet the need, we have developed and characterized a fourfold multiplexed OPA (MOPA4) against 13 serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) of pneumococci. Thirteen target bacteria were made resistant to only one of the following antibiotics: optochin, streptomycin, spectinomycin, and trimethoprim. Following optimization of assay conditions, accuracy of MOPA4 was determined by testing 30 sera from old adults in the MOPA4 and the single-serotype assays. The opsonization titers obtained with both assays agreed well (r(2) > 0.95). Although 22 (out of 390; approximately 6%) results differed more than twofold, the differences were not reproducible. The assay was specific: preabsorbing test sera with homologous polysaccharide (PS) completely abrogated opsonic activity, but a pool of unrelated PS (5 mug/ml of each) had no effect. Intra- and interassay coefficients of variation were 10 and 22%, respectively. MOPA4 results were unaffected by having different target pneumococcal serotypes in each assay group. Also, HL60 cell-to-bacteria ratios could be varied twofold without affecting the results. We conclude that MOPA4 is sensitive, accurate, specific, precise, and robust enough for large-scale clinical studies. Furthermore, MOPA4 should allow evaluation of multivalent pneumococcal vaccines with the limited volume of serum typically available from young children.
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            Validation of a routine opsonophagocytosis assay to predict invasive pneumococcal disease efficacy of conjugate vaccine in children.

            Immunological evaluation of the clinical impact of vaccines designed to protect against infection by Streptococcus pneumoniae requires measurement of serotype-specific functional antibodies. We describe the development and validation of a viable pneumococcal opsonophagocytosis assay (OPA) that can be used for routine serological analysis of paediatric immune responses after immunization. OPA seropositivity (%> or =8 threshold) reflected well invasive pneumococcal disease (IPD) effectiveness. In contrast, the 22F inhibition ELISA seropositivity (%> or =0.20microg/ml threshold) overestimated (19F) or underestimated (6B, 23F, 6A) IPD effectiveness for several serotypes. The seropositivity as estimated by a standardized and highly reproducible OPA was predictive for the serotype-specific IPD efficacy of pneumococcal conjugate vaccines.
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              Emergence of Streptococcus pneumoniae Serotype 12F after Sequential Introduction of 7- and 13-Valent Vaccines, Israel

              Israel implemented use of 7- and 13-valent pneumococcal vaccine in 2009 and 2010, respectively. We describe results of prospective, population-based, nationwide active surveillance of Streptococcus pneumoniae serotype 12F (Sp12F) invasive pneumococcal disease (IPD) dynamics in the 7 years after vaccine introduction. Of 4,573 IPD episodes during July 2009–June 2016, a total of 434 (9.5%) were caused by Sp12F. Sp12F IPD rates (cases/100,000 population) increased in children 3.9 since 2011–2012, followed by an increase in all ages. During 2011–2016, Sp12F was the most prevalent IPD serotype. Sp12F isolates were mostly penicillin nonsusceptible (MIC >0.06 µg/mL; MIC50 = 0.12) and predominantly of sequence type 3774), a clone exclusively found in Israel (constituting ≈90% of isolates in 2000–2009). The sharp increase, long duration, and predominance of Sp12F IPD after vaccine implementation reflect a single clone expansion and may represent more than a transient outbreak.
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                Author and article information

                Journal
                Emerg Microbes Infect
                Emerg Microbes Infect
                Emerging Microbes & Infections
                Taylor & Francis
                2222-1751
                14 October 2020
                2020
                : 9
                : 1
                : 2266-2268
                Affiliations
                [a ]Department of Respiratory Medicine, Nagasaki University Hospital , Nagasaki City, Japan
                [b ]Department of Respiratory Medicine, Sasebo City General Hospital , Sasebo City, Japan
                [c ]Infection Control and Education Center, Nagasaki University Hospital , Nagasaki City, Japan
                [d ]Department of Laboratory Medicine, Nagasaki University Hospital , Nagasaki City, Japan
                [e ]Department of Bacteriology I, National Institute of Infectious Diseases , Shinjuku City, Japan
                Author notes
                [CONTACT ] Kazuko Yamamoto kazukomd@ 123456nagasaki-u.ac.jp Department of Respiratory Medicine, Nagasaki University Hospital , Sakamoto 1-7-1, Nagasaki City, Nagasaki852-8501, Japan
                Author information
                https://orcid.org/0000-0002-1357-1676
                Article
                1830716
                10.1080/22221751.2020.1830716
                7594767
                32990189
                21a59283-4646-4971-b7a0-3cbd645c6760
                © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group, on behalf of Shanghai Shangyixun Cultural Communication Co., Ltd

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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                Page count
                Figures: 1, Tables: 0, Equations: 0, References: 12, Pages: 3
                Categories
                Letter
                Letter

                pneumococcal vaccine,streptococcus pneumoniae infection,streptococcus pneumoniae serotype 12 f,invasive pneumococcal disease,opsonophagocytosis assay

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