An open-label, multicenter study was conducted to describe the safety of the 13-valent pneumococcal conjugate vaccine (PCV13) in 1049 individuals aged ≥68 years, who had previously been immunized with the unconjugate...An open-label, multicenter study was conducted to describe the safety of the 13-valent pneumococcal conjugate vaccine (PCV13) in 1049 individuals aged ≥68 years, who had previously been immunized with the unconjugated 23-valent pneumococcal polysaccharide vaccine (PPSV23). In addition, the safety profile of PCV13 in this study was compared, in a post-hoc descriptive analysis, to that observed in other elderly populations, who had received PCV13 or PPSV23 as part of other completed studies. Local (56.6%) and systemic reactions (58.4%) were very common, but were mainly mild, and of short duration (mean: 1.3 - 4.6 days). There were no related serious adverse events (AEs) within 1 month after PCV13. 123 days after PCV13 and 94 days after a nonstudy influenza vaccine, a case of transient Guillain-Barré syndrome occurred, which the investigator assessed as possibly related to the vaccination. Reactogenicity observed in this study population was generally similar to that of other elderly study populations with PPSV23-preimmunized adults, and with PPSV23-naive adults. Reactogenicity was less common in this study than that observed in PPSV23-preimmunized adults who were revaccinated with PPSV23 rather than a subsequent dose of PCV13. There were no related serious AEs reported after PCV13 and PPSV23 in these comparator studies. Conclusion: PCV13 may be administered safely to older adults previously immunized with PPSV23. (ClinicalTrials. gov Identifier: NCT00500266)展开更多
Pneumonia remains the single leading cause of childhood death worldwide.Despite the commercial availability of multiple pneumococcal conjugate vaccines(PCVs),high dosage cost and supply shortages prevent PCV delivery ...Pneumonia remains the single leading cause of childhood death worldwide.Despite the commercial availability of multiple pneumococcal conjugate vaccines(PCVs),high dosage cost and supply shortages prevent PCV delivery to much of the developing world.The current work presents high-yield pneumococcal conjugates that are immunogenic in animals and suitable for use in human vaccine development.The 13-valent pneumococcal conjugate vaccine(PCV-13)investigated in this research incorporated serotypes 1,3,4,5,6A,6B,7F,9V,14,18C,19A,19F,and 23F.Pneumococcal polysaccharides(PnPSs)and CRM197 carrier protein were produced and purified in-house,and used to prepare PnPS-CRM conjugates using unique,cyanide-free,in vacuo glycation conjugation methods.In vitro characterization confirmed the generation of higher molecular weight PnPS-CRM conjugates low in free protein.In vivo animal studies were performed to compare PnuVax's PCV-13 to the commercially available PCV-13,Prevnar®13(Pfizer,USA).A boost dose was provided to all groups post-dose 1 at t?14 days.Post-dose 2 results at t?28 days showed that all 13 serotypes in PnuVax's PCV-13 were boostable.Per serotype IgG GMCs demonstrated that PnuVax's PCV-13 is immunogenic for all 13 serotypes,with 10 of the 13 serotypes statistically the same or higher than Prevnar®13 post-dose 2.As a result,the novel polysaccharideprotein conjugates developed in this work are highly promising for use in human PCV development.The in vacuo conjugation technique applied in this work could also be readily adapted to develop many other conjugate vaccines.展开更多
目的分析13价肺炎球菌多糖结合疫苗(Pneumococcal polysaccharide conjugate vaccine,PCV13)纳入青海省免疫规划(Expanded Program on Immunization,EPI)的成本效益。方法建立决策树-Markov模型,计算PCV13纳入青海省EPI的2021年出生队...目的分析13价肺炎球菌多糖结合疫苗(Pneumococcal polysaccharide conjugate vaccine,PCV13)纳入青海省免疫规划(Expanded Program on Immunization,EPI)的成本效益。方法建立决策树-Markov模型,计算PCV13纳入青海省EPI的2021年出生队列接种成本和肺炎球菌性疾病(Pneumococcal disease,PD)经济负担,与未纳入EPI相比的净效益和效益成本比(Benefit-cost ratio,BCR)。结果PCV13纳入青海省EPI与未纳入EPI相比,PCV13总接种成本将增加12845万元,PD总经济负担将减少12921万元,产生的净效益为76万元,BCR为1.01。具有成本效益的每剂次PCV13最高价格为460元。结论按照当前国产PCV13价格将PCV13纳入青海省EPI从全社会角度略具有成本效益,建议降低疫苗价格以进一步提高成本效益,适时将PCV13纳入青海省EPI。展开更多
目的研究小鼠模型在评价13价肺炎球菌结合疫苗(pneumococcal conjugate vaccine,PCV)免疫原性中的作用。方法15批13价PCV免疫NIH小鼠,免疫3针后采血,检测血清抗不同血清型荚膜多糖IgG抗体的含量和调理吞噬杀菌抗体的水平。检测方法采用...目的研究小鼠模型在评价13价肺炎球菌结合疫苗(pneumococcal conjugate vaccine,PCV)免疫原性中的作用。方法15批13价PCV免疫NIH小鼠,免疫3针后采血,检测血清抗不同血清型荚膜多糖IgG抗体的含量和调理吞噬杀菌抗体的水平。检测方法采用WHO推荐的ELISA和OPA。系统性比较IgG抗体含量和调理吞噬杀菌滴度之间的相关关系,包括组内相关关系和均值相关关系以及两者之间在统计学上的差异。结果①各型的组内相关性在每个组之间有所不同23F型OPA滴度与IgG抗体水平之间相关系数比较低,而且各组之间的差异均有统计学意义(P均<0.05);3型的相关系数比较高,而且与大部分血清型(如4、6A、6B、9V、14、18C、19F和23F型)之间的差异均有统计学意义(P均<0.05);而7F型和几乎所有的型(23F型除外)之间差异均无统计学意义(P均>0.05)。另外,方差分析结果表明,各型之间总体的差异有统计学意义(P<0.05)。②每组有13个血清型,其在各组之间的差异除了G7组与其他12组的差异有统计学意义之外,其他各组之间的差异几乎没有统计学意义(P均>0.05)。另外,方差分析结果表明,各组之间总体上差异无统计学意义(P=0.17,P>0.05)。③均值相关性和组内相关性的均值有一定的差异,除了5型,其他血清型的均值相关性都高于组内相关性的均值。④对每个组13个血清型的组内相关性与均值相关性之间进行统计学上的差异比较:除了7、8、11组,其余都是均值相关性高。结论对15个组的几何平均滴度(geometric mean titer,GMT)和几何平均ELISA单位(geometric mean ELISA unit,GMU)进行相关性分析,得到均值相关性,均值相关性与组内在各种情况下的差异,说明均值相关性在一定程度上消除了这种个体的影响,能够比较准确地反映OPA滴度与IgG水平之间的相关关系。NIH小鼠作为13价PCV血清学评价的动物模型,其血清的GMU和GMT都能够反映疫苗的免疫原性。展开更多
文摘An open-label, multicenter study was conducted to describe the safety of the 13-valent pneumococcal conjugate vaccine (PCV13) in 1049 individuals aged ≥68 years, who had previously been immunized with the unconjugated 23-valent pneumococcal polysaccharide vaccine (PPSV23). In addition, the safety profile of PCV13 in this study was compared, in a post-hoc descriptive analysis, to that observed in other elderly populations, who had received PCV13 or PPSV23 as part of other completed studies. Local (56.6%) and systemic reactions (58.4%) were very common, but were mainly mild, and of short duration (mean: 1.3 - 4.6 days). There were no related serious adverse events (AEs) within 1 month after PCV13. 123 days after PCV13 and 94 days after a nonstudy influenza vaccine, a case of transient Guillain-Barré syndrome occurred, which the investigator assessed as possibly related to the vaccination. Reactogenicity observed in this study population was generally similar to that of other elderly study populations with PPSV23-preimmunized adults, and with PPSV23-naive adults. Reactogenicity was less common in this study than that observed in PPSV23-preimmunized adults who were revaccinated with PPSV23 rather than a subsequent dose of PCV13. There were no related serious AEs reported after PCV13 and PPSV23 in these comparator studies. Conclusion: PCV13 may be administered safely to older adults previously immunized with PPSV23. (ClinicalTrials. gov Identifier: NCT00500266)
文摘Pneumonia remains the single leading cause of childhood death worldwide.Despite the commercial availability of multiple pneumococcal conjugate vaccines(PCVs),high dosage cost and supply shortages prevent PCV delivery to much of the developing world.The current work presents high-yield pneumococcal conjugates that are immunogenic in animals and suitable for use in human vaccine development.The 13-valent pneumococcal conjugate vaccine(PCV-13)investigated in this research incorporated serotypes 1,3,4,5,6A,6B,7F,9V,14,18C,19A,19F,and 23F.Pneumococcal polysaccharides(PnPSs)and CRM197 carrier protein were produced and purified in-house,and used to prepare PnPS-CRM conjugates using unique,cyanide-free,in vacuo glycation conjugation methods.In vitro characterization confirmed the generation of higher molecular weight PnPS-CRM conjugates low in free protein.In vivo animal studies were performed to compare PnuVax's PCV-13 to the commercially available PCV-13,Prevnar®13(Pfizer,USA).A boost dose was provided to all groups post-dose 1 at t?14 days.Post-dose 2 results at t?28 days showed that all 13 serotypes in PnuVax's PCV-13 were boostable.Per serotype IgG GMCs demonstrated that PnuVax's PCV-13 is immunogenic for all 13 serotypes,with 10 of the 13 serotypes statistically the same or higher than Prevnar®13 post-dose 2.As a result,the novel polysaccharideprotein conjugates developed in this work are highly promising for use in human PCV development.The in vacuo conjugation technique applied in this work could also be readily adapted to develop many other conjugate vaccines.
文摘目的分析13价肺炎球菌多糖结合疫苗(Pneumococcal polysaccharide conjugate vaccine,PCV13)纳入青海省免疫规划(Expanded Program on Immunization,EPI)的成本效益。方法建立决策树-Markov模型,计算PCV13纳入青海省EPI的2021年出生队列接种成本和肺炎球菌性疾病(Pneumococcal disease,PD)经济负担,与未纳入EPI相比的净效益和效益成本比(Benefit-cost ratio,BCR)。结果PCV13纳入青海省EPI与未纳入EPI相比,PCV13总接种成本将增加12845万元,PD总经济负担将减少12921万元,产生的净效益为76万元,BCR为1.01。具有成本效益的每剂次PCV13最高价格为460元。结论按照当前国产PCV13价格将PCV13纳入青海省EPI从全社会角度略具有成本效益,建议降低疫苗价格以进一步提高成本效益,适时将PCV13纳入青海省EPI。
文摘目的研究小鼠模型在评价13价肺炎球菌结合疫苗(pneumococcal conjugate vaccine,PCV)免疫原性中的作用。方法15批13价PCV免疫NIH小鼠,免疫3针后采血,检测血清抗不同血清型荚膜多糖IgG抗体的含量和调理吞噬杀菌抗体的水平。检测方法采用WHO推荐的ELISA和OPA。系统性比较IgG抗体含量和调理吞噬杀菌滴度之间的相关关系,包括组内相关关系和均值相关关系以及两者之间在统计学上的差异。结果①各型的组内相关性在每个组之间有所不同23F型OPA滴度与IgG抗体水平之间相关系数比较低,而且各组之间的差异均有统计学意义(P均<0.05);3型的相关系数比较高,而且与大部分血清型(如4、6A、6B、9V、14、18C、19F和23F型)之间的差异均有统计学意义(P均<0.05);而7F型和几乎所有的型(23F型除外)之间差异均无统计学意义(P均>0.05)。另外,方差分析结果表明,各型之间总体的差异有统计学意义(P<0.05)。②每组有13个血清型,其在各组之间的差异除了G7组与其他12组的差异有统计学意义之外,其他各组之间的差异几乎没有统计学意义(P均>0.05)。另外,方差分析结果表明,各组之间总体上差异无统计学意义(P=0.17,P>0.05)。③均值相关性和组内相关性的均值有一定的差异,除了5型,其他血清型的均值相关性都高于组内相关性的均值。④对每个组13个血清型的组内相关性与均值相关性之间进行统计学上的差异比较:除了7、8、11组,其余都是均值相关性高。结论对15个组的几何平均滴度(geometric mean titer,GMT)和几何平均ELISA单位(geometric mean ELISA unit,GMU)进行相关性分析,得到均值相关性,均值相关性与组内在各种情况下的差异,说明均值相关性在一定程度上消除了这种个体的影响,能够比较准确地反映OPA滴度与IgG水平之间的相关关系。NIH小鼠作为13价PCV血清学评价的动物模型,其血清的GMU和GMT都能够反映疫苗的免疫原性。
