• Clinical and Experimental Pediatrics
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• 제57권2호
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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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• 제29권1호
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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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• 제54권4호
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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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• 제50권4호
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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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• 제63권7호
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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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• 제33권51호
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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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• 제51권6호
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• pp.622-628
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• 2008

목 적 : 본 연구는 우리나라 소아에서 면역원성에 근거한 추가접종의 필요성 여부를 확인하고자 하였다. 방 법 : 2006년 9월부터 2006년 12월까지 강남 차병원에 내원하여 검사를 위해 혈액 채취의 기회가 있었던 12-23개월 사이의 소아 39명을 대상으로 하였다. 7가 폐렴사슬알균 단백결합 백신의 접종력에 따라 기초접종 군과 추가접종 군으로 나누었다. 백신에 포함된 혈청형(4, 6B, 9V, 14, 18C, 19F, 23F)에 대하여 각각의 폐렴사슬알균 피막다당질 항체를 3세대 효소면역측정법으로 측정하였다. 결 과 : 각 혈청형에 대한 폐렴사슬알균 피막다당질 항체의 기하평균은 기초접종만 완료한 군보다 추가접종을 완료한 군에서 높았다(P<0.05). 폐렴사슬알균 피막다당질 항체가가 $0.35{\mu}g/mL$ 이상인 비율은 기초접종과 추가접종 군 모두에서 90.5-100%였다. 폐렴사슬알균 피막다당질 항체가가 $1.0{\mu}g/mL$ 이상인 비율은 추가접종 군에서 94.4-100%로 혈청형 6B와 14를 제외하고는 기초접종 군 보다 높았다(P<0.05). 폐렴사슬알균 피막다당질 항체가가 $5.0{\mu}g/mL$ 이상인 비율은 추가접종 군에서 50.0-94.4%로 모든 혈청형에서 기초접종 군 보다 높았다(P<0.05). 결 론 : 우리나라 소아에서 추가접종 후의 면역원성은 매우 좋았고 기초접종 이후에도 비교적 좋음을 알 수 있었다. 우리나라에 폐렴사슬알균 단백결합 백신의 도입과 접종 횟수를 결정하기 위해서는 전향적인 면역원성 연구가 지속되어야 할 것이라 생각된다.

• Clinical and Experimental Pediatrics
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• 제52권4호
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• pp.508-511
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• 2009

폐구균(Streptococcus pneumoniae)은 소아, 특히 어린 영아에서 심한 침습성 질병을 일으키는 중요한 원인균이다. 2003년부터 우리나라에서 접종하기 시작한 7가 폐구균백신(PCV7)은 소아에서 침습성 폐구균성 폐렴과 수막염을 예방하는 것으로 알려져 왔다. 그러나 최근 7가 폐구균백신을 접종한 이후부터 비7가 폐구균 혈청형(non-PCV7 serotype) 감염 발생률이 증가하고 있다. 14개월 된 여아가 내원 3일 전부터 열과 구토가 있었으나 증상 치료만 하고 있던 중 갑작스런 의식불명과 기면(lethargy)으로 응급실로 내원하였다. 입원 후 즉각적인 진단과 치료를 시행했음에도 불구하고 환자는 빠르게 혼수와 뇌사 상태로 진행하였다. 환자는 이전에 3회의 7가 폐구균백신을 접종하였으나 최종 진단은 비7가 폐구균 혈청형인 폐구균 19A 수막염이었고, 입원 20일째 사망하였다. 이는 한국에서 문헌상 보고된 적이 없는, 폐구균 19A 혈청형 수막염으로 사망한 첫번째 증례이므로 이에 보고하는 바이다.

• Clinical and Experimental Pediatrics
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• 제54권4호
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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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• 제10권2호
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• pp.159-166
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• 2003

목 적 : 폐구균은 비인두에 존재하는 정상균주이나 중이염 등의 국소 감염 뿐 아니라 폐렴, 뇌수막염, 패혈증 등의 침습성 질환을 유발하는 것으로 알려져 있다. 최근 전 세계적으로 다제내성 폐구균이 증가하는 추세를 보여 큰 문제가 되고 있는바 이에 저자들은 폐구균의 혈청형과 항생제 감수성을 검사하고, 향후 시행될 폐구균 예방접종의 효용성 등을 예측해 보고자 하였다. 방 법 : 2001년 9월부터 2003년 1월까지 연세의료원에 내원한 환자 중 배양 검사상 폐구균이 검출된 116명을 대상으로 하였다. 폐구균의 혈청형 검사는 Quellung 반응을 통해 결정하였고, 페니실린 내성 여부는 oxacillin 디스크 확산법으로 판정하였다. 결 과 : 폐구균은 객담 76례(65.5%), 혈액 13례(11.2%), 이루 12례(10.3%), 인두 7례(6.0%), 비강 2례(1.7%), 뇌척수액, 안구분비물, 복수, 수술 후 창상부위, 두부 농양, 도관 각 1례(0.9%)로 총 116례에서 배양되었으며, 98례에서 혈청형 검사가 가능하였다. 분리된 혈청형을 살펴보면 19F 15례(15.3%), 19A 11례(11.2%), 11A 8례(8.2%), 6A, 14와 3이 각 7례(7.1%), 6B, 23F와 35가 각 6례(6.1%)의 순이었다. 총 116례 중 82례(70.7%)에서 페니실린 내성을 보였으며, 페니실린 내성균주의 혈청형은 19F, 19A, 11A, 23F, 6A, 9V등이 49례(59.8%)를 차지하였고, cotrimoxazole(74.4%), tetracycline(69.5%), erythromycin(90.3%) 등의 다른 항생제에도 높은 내성률을 보였다. 소아 환자 22례 중 20례에서 혈청형 분석이 가능하였고, 19A, 19F가 각 5례(25.0%), 6A, 6B, 23F가 각 2례(10.0%), 11A, 14, 19, 29가 각 1례(5.0%)를 차지하여 7가 폐구균 단백결합백신에 포함되는 혈청형이 50%(10/20), 백신관련 혈청형을 포함하여 85%(17/20)이었으며, 22례 중 86.4%(19/22)에서 페니실린 내성을 보였다. 결 론 : 이전의 보고에 비해 백신포함 혈청형의 빈도가 약간 낮은 소견을 보였으며, 최근 일부 폐구균 혈청형의 변화가 보고되고 있는 바 7가 폐구균 단백결합 백신의 상용화에 앞서 전국적인 폐구균 혈청형의 조사가 필요할 것으로 사료된다.