• Journal of Microbiology and Biotechnology
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• 제13권3호
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• pp.469-472
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• 2003

A method that effectively precipitates capsular polysaccharide of Haemophilus influenzae type b (polyribosylribitol phosphate, PRP) conjugated to tetanus toxoid (TT), PRP TT in a liquid vaccine has been developed to measure free PRP present in TT-conjugate vaccine. The method involves adding anti-TT antibody and ammonium sulfate to precipitate PRP-TT conjugate and measuring free PRP in tile supernatant. This new method provides a complete precipitation of the total PRP-TT, and provides an accurate and reproducible measurements of free PRP. The accuracy of the assay was confirmed by spiking known amounts of unconjugated PRP to PRP-TT conjugate, and the new method was found to have no effect on free PRP while precipitating PRP-TT. The published acid precipitation method did not produce reproducible results due to incomplete precipitation of PRP-TT, especially when the vaccine is formulated in a salt-buffered solution.

• Childhood Kidney Diseases
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• 제6권1호
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• pp.56-60
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• 2002

Streptococcus pneumoniae(폐렴구균)는 소아에서 심각한 질별을 초래하는 주 원인 중의 하나이며, 면역결핍이나 만성 질환을 동반한 환아에서는 낮은 항체가로 인해 침습적 감염의 위험이 더욱 크다. 신증후군 환아에서도 폐렴구균은 중요한 병인균의 하나로, 특히 원발성 복막염의 주요한 원인균이다. 최근까지 23가의 polysaccharide pneumococcal vaccine이 복막염 예방 목적으로 추천되어 왔으나, 새로이 7가의 conjugate vaccine이 소개되면서 신증후군 환아에서 폐렴구균 예방접종의 정립이 필요하다고 생각되어, 현재까지 접종받은 환아들의 의무 기록을 검토하였다. 1980년 이후 20년간 23가의 polysaccharide pneumococcal vaccine을 접종 받은 2세에서 18세 사이의 55명의 환아들을 평균 38.5개월 간 추적 관찰하였다. 폐렴구균에 의한 복막염은 발생하지 않아 임상적으로 효과가 있는 것으로 생각되며, 향후로 conjugate vaccine이 국내에서 상용화되기 전까지 병용하여도 안전할 것으로 생각된다.

• Clinical and Experimental Pediatrics
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• 제49권3호
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• pp.235-241
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• 2006

Streptococus pneumoniae is an important cause of invasive infections as well as non-invasive infections such as acute otitis media and sinusitis both in children and adults. Resistance of S. pneumoniae to multiple antimicrobials is increasing and poses therapeutic challenges, and prevention became more important. 23-valent polysaccharide vaccine has been used for the last several decades, but is not effective in children <2 years of age, the highest risk group of invasive diseases. Recently, a 7-valent pneumococcal protein conjugate vaccine(PCV) which is effective in infants and young children has been developed. The efficacy of PCVs against invasive pneumococcal disease and pneumonia is well established and is documented in several well-conducted studies. However, the effect of PCVs on otitis media is less obvious and more complex. PCVs clearly reduce diseases caused by vaccine-type(VT) pneumococci, but replacement of VT serotypes by non-VT serotypes in nasopharyngeal carriage of S. pneumoniae is responsible for the increase in acute otitis media caused by non-VT serotypes. Three years after introduction of PCV in the US, some increase of invasive infections with serotype 19A possibly due to serotype switching within certain vaccine type strains has been noted. Since most antibiotic-resistance in S. pneumoniae is confined to VT serotypes, vaccine use also reduces antibiotic resistance. With development of PCV, there was a great advance in the prevention of pneumococcal diseases, but replacement with potential virulent organisms and development of antibiotic resistance in non-VT pneumococci is a possibility that needs careful monitoring.

• Pediatric Infection and Vaccine
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• 제15권1호
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• pp.1-4
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• 2008

Immunizations are among the most cost-effective and widely used public health interventions. This is a report a revision of recommendation of immunization for children by Korean Pediatric Society. Immunization. Vaccines were divided into 4 groups. 1) Vaccines that are recommended to all infants and children (BCG, hepatitis B vaccine, DTaP, Td, Polio vaccine, Japanese encephalitis vaccine, MMR, varicella vaccine, influenza vaccine [6-23 months of age], H. influenzae type b vaccine), 2) those that can be administered to all infants and children, but decision of administration is made by parents (pneumococcal conjugate vaccine, hepatitis A vaccine, influenza vaccine [healthy children ${\geq}24$ months of age], rotavirus vaccine, human papilloma virus vaccine), 3) those that should be given to high risk group (pneumococcal polysaccharide vaccine [high risk patients ${\geq}24$ months of age], influenza vaccine [high risk patients ${\geq}24$ months of age], typhoid vaccine), and 4) those administered for control of outbreaks or prevention of emerging infectious diseases. Immunization schedule recommended by Korean Pediatric Society in 2008 is presented.

• 약학회지
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• 제48권6호
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• pp.345-351
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• 2004

ln the present work to determine effect of a Streptococcus pneumoniae conjugate vaccine, S.pneumoniae capsule attached to the surface protein (JY-Pol) was ex amined. This JY-Pol contained approximately 92% and 6% carbohydrate and protein, respectively. Gel electrophoresis revealed the presence of the surface protein in the JY-Pol. By the double immunodiffusion and isotyping ELISA analyses, administration of JY-Pol that was adsorbed to alum adjuvant (JY-Pol/Alum) into mice induced IgM, IgG, and IgA specific for the S.pneumoniae capsule. The ATCC capsular polysaccharide adsorbed to alum (ATCC-Pol/Alum) provoked only IgM in mice. In survival tests, mice that were immunized with the JY-Pol/Alum before intravenous challenge with live S.pneumoniae survived entire period of 46 day-observation, whereas all mice that received ATCC-Pol/Alum or only diluent instead of the vaccination died within 5 and 12 days, respectively. Results from footpad-edema test showed that JY-Pol/Alum formula provoked the cellular immunity as determined by swelling of the mouse footpad. These data indicate that the naturally conjugated JY- Pol enhances resistance of mice against disseminated pneumococcal disease due to S.pneumoniae by both humoral and cellular immune responses.

• 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.

• 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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• 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.

• Pediatric Infection and Vaccine
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• 제20권2호
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• pp.53-62
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• 2013

목 적 : 폐구균 단백결합 백신의 교차혈청형에 대한 교차방어 능력에 대한 연구는 매우 부족하다. 본 연구는 12-23개월 연령 소아에게 PCV7 추가접종 후 얻어진 면역혈청에서 교차혈청형 6A, 6C, 19A에 대한 교차 항체의 혈청학적 특성을 연구하기 위해 수행하였다. 방 법 : 백신 혈청형 6B, 19F와 교차혈청형 6A, 6C, 19A의 IgG, IgM 항체 농도와 옵소닌 인덱스를 ELISA와 OPA를 통해 측정하였다. 혈청군 6과 19에 대한 방어항체의 혈청학적 특성과 항원 특이도는 면역혈청내 IgM 제거, OPA, cOPA를 통해 확인하였다. 결 과 : 대조군 혈청에 비교하여 IgM 제거 면역혈청의 6B와 19F에 대한 옵소닌 인덱스가 감소하였고, 6A, 6C, 19A에 대한 옵소닌 인덱스도 역시 감소하였다. cOPA에서 6B 다당질, 19F다당질은 백신 혈청형 6B, 19F 뿐 아니라 6A, 6C, 19A의 방어 면역도 완전히 억제하였다. 결 론 : 6B, 19F를 포함한 PCV7은 교차혈청형 6A, 6C, 19A에 대한 IgG 및 IgM 교차방어 항체를 유도하였다. IgM 방어항체는 IgG 항체와 비교하여 백신 혈청형뿐 아니라 백신-연관 혈청형에 대해 더 높은 옵소닌 인덱스를 나타내었다. 향후 더 많은 소아와 성인의 면역 혈청으로 연구가 필요하다.

• Pediatric Infection and Vaccine
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• 제10권1호
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• pp.71-80
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• 2003

목 적 : b형 Haemophilus influenzae(Hib)의 피막 다당질인 polyribosyl -ribitol-phosphate(PRP)가 Hib 질환의 발병기전에 중요한 역할을 하며, 이에 대한 항체가 있으면 Hib 질환을 예방할 수 있다. Hib 질환을 예방하기 위해 개발된 단백 결합 백신에는 PRP-D, PRP-T, PRP-OMP 및 PRP-CRM197 등이 있다. Hib 피막 다당질에 대한 항체 반응은 백신에 사용된 결합 단백의 종류에 따라 다르지만 인종이나 제조 회사에 따라서 유효성 및 안전성에 차이가 있을 수 있다. PRP-T에는 기존에 국내에 공급되던 $ActHib^{(R)}$(Aventis)와 최근에 국내에 도입되기 시작한 $Hiberix^{TM}$(GlaxoSmithKline Biologicals)가 있다. 본 연구에서는 우리나라 영아에서 PRP-T 백신인 $Hiberix^{TM}$의 면역원성 및 안전성을 평가하고자 하였다. 방 법 : 2001년 3월부터 2002년 4월까지 소아과에 예방접종을 위해 내원한 건강한 생후 2개월 이상의 영아 73명(남아 43명)을 대상으로 하였다. 생후 2, 4, 6개월에 PRP-T 백신($Hiberix^{TM}$)을 필요한 경우에 DTaP, TOPV, B형 간염백신과 같이 접종하였고, 1회 접종 전(2개월), 2회 접종 2개월 후(생후 6개월) 그리고 3회 접종 1개월 후(생후 7개월)에 혈청내 항 PRP 항체가를 효소면역법(ELISA)으로 측정하였다. 매 접종 후 72시간내에 발생하는 국소적, 전신적 이상반응을 관찰하였다. 면역원성은 계획한대로 접종을 완료한 영아에 대하여 분석하였으며, 이상반응은 1회 이상 접종받은 모든 영아에 대하여 분석하였다. 결 과 : 73명 중 63명(남아 37명)이 계획한대로 접종을 완료하였다. 생후 2개월에 측정한 접종 전항 PRP 항체가의 기하 평균치는 0.17 ${\mu}g/mL$(95% CI; 0.13~0.22)이었다. 2회 접종 후(생후 6개월) 항체가의 기하 평균치는 4.14 ${\mu}g/mL$(95% CI; 2.65~6.48), 3회 접종 후(생후 7개월)의 기하 평균치는 14.65 ${\mu}g/mL$(95% CI; 10.83~19.81)이었다. 항체가가 1.0 ${\mu}g/mL$ 이상인 비율은 2회 접종 후 77.8% (95% CI; 67.5~88.0), 3회 접종 후 98.4%(95% CI;95.3~100)이었다. 백신 접종 후 발생한 이상반응중 전신반응으로서 보챔(45.5%)이 가장 많았고 졸음(30.5%), 수유감소(26.7%), 발열(5.6%) 순이었다. 국소반응으로서 동통이 7.9%, 발적(${\geq}5$ mm) 2.8%, 부종(${\geq}5$ mm) 1.8% 순이었다. 이러한 이상반응은 대부분 경증으로 모두 회복되었다. 결 론 : 결론적으로, PRP-T 백신인 $Hiberix^{TM}$는 우리나라 영아에서 우수한 면역원성과 안전성을 보였으며, 특히 2회 접종으로도 항체가의 기하 평균치가 장기적인 방어 수준으로 상승함은 과거의 다른 PRP-T 백신($ActHib^{(R)}$)의 연구 결과들과 일치하는 소견으로 향후 국내에서 PRP-T 백신의 접종 방법에 대한 재고가 필요하다고 사료된다.