• Clinical and Experimental Pediatrics
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• v.57 no.2
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• pp.55-66
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• 2014

The 7-valent pneumococcal protein conjugate vaccine (PCV7) has been shown to be highly efficacious against invasive pneumococcal diseases and effective against pneumonia and in reducing otitis media. The introduction of PCV7 has resulted in major changes in the epidemiology of pneumococcal diseases. However, pneumococcal vaccines induce serotype-specific immunity, and a relative increase in non-vaccine serotypes has been reported following the widespread use of PCV7, leading to a need for extended serotype coverage for protection. PCV10 and PCV13 have been licensed on the basis of noninferiority of immunogenicity compared to a licensed conjugate vaccine. In this article, we aimed to review important data regarding the efficacy and effectiveness of the extended-coverage PCVs published or reported thus far and to discuss future implications for pneumococcal vaccines in Korea. After the introduction of PCV10 and PCV13, within a short period of time, evidence of protection conferred by these vaccines against invasive and mucosal infections caused by most of the serotypes included in the vaccines is accumulating. The choice of vaccine should be based on the changes in the dynamics of pneumococcal serotype distribution and diseases in the region where the vaccines are to be used. Continuous surveillance is essential for the appropriate use of pneumococcal vaccines and evaluation of the impact of PCVs on pneumococcal diseases.

• Journal of Yeungnam Medical Science
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• v.29 no.1
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• pp.1-8
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• 2012

Streptococcus pneumonia is a very important pathogen for children and elderly people. Two types of pneumococcal vaccines are available in the market: pneumococcal polysaccharide vaccine (PPSV) and pneumococcal conjugate vaccine (PCV). PPSVs have been used for more than 30 years, and PCVs for about 10 years. There have been many reports concerning the evaluation of the vaccines' efficacies in preventing pneumococcal diseases such as meningitis, pneumonia, and otitis media and bacteremia, but the clinical trials had been performed with different conditions, such as diverse vaccine valencies, age groups, races, target outcomes, immunological cut-off values, and follow-up periods. PPSV is recommended for elderly people and chronic disease patients such as asthma, diabetes mellitus, chronic renal failure, and hyposplenic patients. According to the data from several systemic reviews and population-based surveillances, PPSV is effective for pneumococcal pneumonia and vaccine-type bacteremia among healthy adults. Until now, however, there is insufficient evidence of the effectiveness of PPSV among high-risk adults. PCV is very effective in preventing vaccine-type invasive pneumococcal disease (IPD) among children, but its efficacy for pneumonia is very low among children. The incidence of vaccine-related or non-vaccine-type IPDs is increasing after the introduction of 7-valent PCV (PCV7) as a routine immunization for children. Recently, 10- and 13-valent PCVs have been used for children, instead of PCV7. Therefore, continuous surveillance for serotype change among pneumococcal diseases is necessary to evaluate the vaccines' efficacy.

• Clinical and Experimental Pediatrics
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• v.54 no.4
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• pp.146-151
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• 2011

Streptococcus pneumoniae remains a leading cause of invasive infections including bacteremia and meningitis, as well as mucosal infections such as otitis media and pneumonia among children and adults. The 7-valent pneumococcal conjugate vaccine (PCV7) was licensed for use among infants and young children in many countries including Korea. The routine use of PCV7 has resulted in a decreased incidence of invasive pneumococcal disease (IPD) by the vaccine serotypes among the vaccinees and substantial declines in IPD among unvaccinated populations such as older children and adults as well. In addition, there are increasing evidences to suggest that routine immunization with PCV7 is changing the epidemiology of pneumococcal diseases such as serotype distribution of IPD, nasopharyngeal colonization, and antibiotic resistance patterns. In contrast, there is an increase in the number of IPDs caused by nonvaccine serotypes, though it is much smaller than overall declines of vaccine serotype diseases. Several vaccines containing additional serotypes have been developed and tested clinically in order to expand the range of serotypes of Streptococcus pneumoniae. Recently two new pneumococcal protein conjugate vaccines, 10-valent pneumococcal conjugate vaccine (PCV10) and 13-valent pneumococcal conjugate vaccine (PCV13), have been approved for use in several countries including Korea. This report summarizes the recommendations approved by the Committee on Infectious Diseases, the Korean Pediatric Society.

• Infection and chemotherapy
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• v.50 no.4
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• pp.328-339
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• 2018

Background: Pneumococcal disease is a major cause of morbidity and mortality worldwide, especially in patients with comorbidities and advanced age. This study evaluated trends in epidemiology of adult pneumococcal disease in Crete, Greece, by identifying serotype distribution and antimicrobial resistance of consecutive Streptococcus pneumoniae strains isolated from adults during an 8-year time period (2009-2016) and the indirect effect of the infant pneumococcal higher-valent conjugate vaccines 10-valent pneumococcal conjugate vaccine (PCV10) and 13-valent pneumococcal conjugate vaccine (PCV13). Materials and Methods: Antimicrobial susceptibility was performed by E-test and serotyping by Quellung reaction. Multidrug resistance (MDR) was defined as non-susceptibility to penicillin (PNSP) combined with resistance to ${\geq}2$ non-${\beta}$-lactam antimicrobials. Results: A total of 135 S. pneumoniae strains were isolated from adults during the study period. Twenty-one serotypes were identified with 17F, 15A, 3, 19A, and 11A, being the most common. The coverage rates of PCV10, and PCV13 were 17.8% and 37.8%, respectively. PCV13 serotypes decreased significantly from 68.4% in 2009 to 8.3% in 2016 (P = 0.002). The most important emerging non-PCV13 serotypes were 17F, 15A, and 11A, with 15A being strongly associated with antimicrobial resistance and MDR. Among all study isolates, penicillin-resistant and MDR strains represented 7.4% and 14.1%, respectively. Predominant PNSP serotypes were 19A (21.7%), 11A (17.4%), and 15A (17.4%). Erythromycin, clindamycin, tetracycline, trimethoprim-sulfamethoxazole, and levofloxacin resistant rates were 30.4%, 15.6%, 16.3%, 16.3%, and 1.5%, respectively. Conclusion: Although pneumococcal disease continues to be a health burden in adults in Crete, our study reveals a herd protection effect of the infant pneumococcal higher-valent conjugate vaccination. Surveillance of changes in serotype distribution and antimicrobial resistance among pneumococcal isolates are necessary to guide optimal prevention and treatment strategies.

• Clinical and Experimental Pediatrics
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• v.63 no.7
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• pp.265-271
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• 2020

Background: Pneumococcal diseases among children aged <5 years worldwide are associated with high annual mortality rates. Purpose: This study aimed to evaluate the immunogenicity and safety of GBP411, a 12-valent pneumococcal conjugant vaccine, with a dosing schedule of 2 primary doses plus 1 booster dose (2p+1) in healthy infants. Methods: This randomized active-controlled (Prevnar 13) double-blind phase 2 trial enrolled healthy subjects aged 6-10 weeks. Three serum concentrations of pneumococcal serotype-specific immunoglobulin G (IgG) were evaluated using the pneumococcal serotype-specific pneumonia polysaccharide enzyme-linked immunosorbent assay at 1 month after the primary doses and before and 1 month after the booster dose. The pneumococcal serotype-specific IgG titer was evaluated using a multiplex opsonophagocytic assay in a subset of 15 subjects per group. Results: After administration of the primary doses, the proportion of subjects who achieved pneumococcal serotype-specific IgG concentrations of >0.35 ㎍/mL was lower for some serotypes in the GBP411 group than in the comparator group (6B: 20.83% vs. 39.22%, P=0.047 and 19A: 58.33% vs. 90.20%, P<0.001). However, after administration of the booster dose, >97% of the subjects in each group achieved IgG concentrations of ≥0.35 ㎍/mL for all 12 serotypes. Increased immunogenicity was observed for some serotypes that showed significant intergroup differences after administration of the primary doses but not after the booster dose. We also found no significant intergroup difference in the overall incidence of solicited local adverse events. Furthermore, the overall incidence of solicited systemic adverse events was significantly lower in the GBP411 group than in the comparator vaccine group (79.59% vs. 98.04%; P=0.003). Conclusion: The GBP411 vaccine with a dosing schedule of 2p+1 may be immunogenic and safe for healthy infants.

• Journal of Korean Medical Science
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• v.33 no.51
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• pp.340.1-340.14
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• 2018

Background: Various pneumococcal vaccines have been evaluated for immunogenicity by opsonophagocytic assay (OPA). A multiplexed OPA (MOPA) for 13 pneumococcal serotypes was developed by Nahm and Burton, and expanded to 26 serotypes in 2012. The development of new conjugate vaccines with increased valence has necessitated expanded MOPAs to include these additional serotypes. In this study, we validated this expanded MOPA platform and applied to measure antibodies against 11 additional serotypes (2, 8, 9N, 10A, 11A, 12F, 15B, 17F, 20B, 22F, and 33F) in human sera. Methods: All materials, including serum, complement, bacterial master stocks, and HL-60 cells, were evaluated for assay optimization. Following optimization, the assay was validated for accuracy, specificity, and intra- and inter-assay precision with sera from adult donors following standard protocols. The assay was applied to evaluate functional antibodies of 42 sera immunized with 23-valent pneumococcal polysaccharide vaccine (PPV23). Results: The expanded MOPA platform was specific for all serotypes, with the exception of serotype 20. The assay results were highly correlated with those obtained from single-serotype OPA, indicating acceptable accuracy. The coefficients of variation were 7%-24% and 13%-39% in tests of intra- and inter-assay precision, respectively, using three quality-control samples. A MOPA that included 11 additional serotypes in the PPV23 was established and validated with respect to accuracy, specificity, and precision. The opsonic indices of immune sera were obtained using this validated assay. Conclusion: The expanded MOPA will be useful for evaluation of the immunogenicity of PPV23 and future conjugate vaccine formulations.

• Clinical and Experimental Pediatrics
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• v.51 no.6
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• pp.622-628
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• 2008

Purpose : The purpose of this study was to evaluate the immunogenicity of the booster immunization with pneumococcal conjugate vaccine in Korean children. Methods : Thirty-nine children aged 12-23 months who visited Kangnam CHA Hospital between September 2006 and December 2006 were enrolled. The children were divided into primary and booster groups depending on their vaccination status for the 7-valent pneumococcal conjugate vaccine. The anti-pneumococcal antibody levels of each serotype included in the vaccine (4, 6B, 9V, 14, 18C, 19F, 23F) were determined by third-generation ELISA. Results : The geometric mean titer (GMT) of antibodies to each pneumococcal serotype in the booster group was higher than in the primary group (P<.05). The percentage of subjects with pneumococcal antibodies ${\geq}0.35{\mu}g/mL$ was 90.5-100% for all serotypes in both the primary and booster groups. The percentage of subjects with pneumococcal antibodies ${\geq}1.0g/mL$ in the booster group was 94.4-100%, which was higher than the primary group except for serotypes 6B and 14 (P<.05). The percentage of subjects with pneumococcal antibodies ${\geq}5.0{\mu}g/mL$ in the booster group was 50.0-94.4% which was higher than the primary group for all serotypes (P<0.05). Conclusion : The immunogenicity of a booster dose of the pneumococcal conjugate vaccine in Korean children was high and the immunogenicity of a primary series was also relatively high. To determine the feasibility of the introduction of the pneumococcal conjugate vaccine and the appropriate schedule for Korean children, further prospective investigation of the immunogenicity of the booster immunization is needed.

• Clinical and Experimental Pediatrics
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• v.52 no.4
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• pp.508-511
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• 2009

Streptococcus pneumoniae is a major cause of serious invasive diseases in children, especially in young infants, but seven- valent pneumococcal conjugate vaccine (PCV7) is believed to prevent invasive pneumococcal pneumonia and meningitis in young children. However, recently, the incidence of non-PCV7 serotype has increased after PCV7 vaccination. A 14-month- old female patient presented at our emergency room with mental change and lethargy. Three days previously, she had developed fever and vomiting. After being admitted, she rapidly progressed to coma and brain death despite prompt and extensive supportive treatment. She expired 20 days after admission with a final diagnosis of pneumococcal 19A (non-PCV7 serotype) meningoencephalitis despite having received PCV7 ($Prevenar^{(R)}$) vaccinations on three occasions. The author reports this first fatality due to pneumococcal 19A meningoencephalitis in Korea and provides a brief review of the literature.

• Clinical and Experimental Pediatrics
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• v.54 no.4
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• pp.163-168
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• 2011

Purpose: The purpose of this study was to evaluate the immune response to serotype 19A in children aged 12-23 months after immunization of the 19F containing 7-valent pneumococcal conjugate vaccine (PCV7). Methods: Blood samples from a total of 45 subjects (age 12-23 months) were included in the study. Subjects were categorized according to immunization status into three groups as follows: 18 subjects with 3 primary doses and 1 booster dose of PCV7 (booster group), 21 subjects with 3 primary doses before 12 months of age (primary group), and 6 subjects with no vaccination history of PCV7 (control group). An ELISA and opsonophagocytic killing assay (OPKA) was done to evaluate the immune responses against serotypes 19F and 19A. Results: According to the ELISA, all subjects had antibody titers ${\geq}0.35{\mu}g/mL$ for serotypes 19F and 19A in the booster and primary group and 83.0% and 66.7% in the control group, respectively. According to the OPKA, subjects with opsonic activity (${\geq}20$) against serotypes 19F and 19A were 100% and 61.1% of the subjects in the booster group and 66.7% and 19.0% in the primary group, respectively. No subjects in the control group had opsonic antibodies against both serotypes. Conclusion: In conclusion, in children 12-23 months age who were previously vaccinated with PCV7, a cross-reactive immune response is elicited against serotype 19A after a primary series of 3 doses in a small proportion of subjects, and this response is amplified after booster vaccination.

• Pediatric Infection and Vaccine
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• v.10 no.2
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• pp.159-166
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• 2003

Purpose : Streptococcus pneumoniae is part of the normal flora but is also responsible for causing many invasive diseases such as pneumonia, meningitis, and sepsis in addition to noninvasive diseases such as otitis in children. Multi-drug resistant strains has raised a lot of concern worldwide and thus the importance of prevention has been emphasized. We have analyzed the current serotypes and antibiotic sensitivity of each serotype as a baseline study to estimate the efficacy of the pneumococcal vaccine in Korean children. Methods : One hundred sixteen cases of pneumococcus cultured at Yonsei Medical Center from September 2001 to January 2003 were analyzed. The serotyping was done with the Quellung reaction and penicillin resistance was tested using the oxacillin disc diffusion method. Results : Pneumococcus were cultured from the sputum in 76 cases(65.5%), from the blood in 13 cases(11.2%), from the ear discharge in 12 cases(10.3%), from the throat in 7 cases(6.0%), from the nasal cavity in 2 cases(1.7%), and one case(0.9%) each from the cerebrospinal fluid, eye discharge, peritoneal fluid, post-operational wound, brain abscess, and catheter tip. Serotyping was possible with 98 cases and the following serotypes were found; 15 cases of type 19F(15.3%), 11 cases of 19A(11.2%), 8 cases of 11A(8.2%), 7 cases each of 6A, 14 and 3(7.1%), 6 cases each of 35, 6B and 23F(6.1%). Eighty two cases(70.7%) out of 116 cases were penicillin resistant and serotypes 19F, 19A, 11A, 23F, 6A, 9V constituted the majority, 48 cases(59.8%). These serotypes showed resistance to cotrimoxazole (74.4%), tetracycline(69.5%), and erythromycin(90.3%) as well. In the 22 cases cultured from children, 19A and 19F were found in 25.0%, 6A, 6B, and 23F in 10.0%, 11A, 14, 19, and 29 in 5.0%. Fifty percent(10/20) of the clinical isolates were represented in the current 7-valent pneumococcal protein conjugate vaccine, and 85%(17/20) when the cross-reacting serotypes were included. Penicillin resistance was found in 86.4%(19/22). Conclusion : The percentage of serotypes included in the 7 valent pneumococcal protein conjugate vaccine found in our study was 40.8% which was less than other prior studies. In anticipation of a change of pneumococcal serotypes, a nationwide multicenter study is needed before the initiation of pneumococcal vaccines in Korea.