A群C群脑膜炎球菌结合疫苗安全性和免疫原性

目的评价A群C群脑膜炎球菌结合疫苗的安全性和免疫原性。方法于2016年5月—2017年9月,选取江苏省淮安市涟水县辖区内1 799名3月龄～5岁婴幼儿进行III期临床试验,按照1:1的比例随机接种试验或对照疫苗。其中3～5月龄和6～11月龄试验组受试者在18月龄时进行加强免疫。每针次接种后对受试者进行安全性观察,并采集各年龄组受试者免疫前、基础免疫后28 d以及3～5月龄和6～11月龄组受试者18月龄和加强免疫后28 d的血清样本进行免疫原性观察。结果 2～5岁、12～23月龄、6～11月龄和3～5月龄试验组,总体征集性不良反应发生率分别为33.11%,58.28%,75.33%和85.62%,以1级(轻度)不良反应为主,试验组与对照组比较差异均无统计学意义;基础免疫后,各试验组A群抗体阳转率分别为98.60%,100%,100%和96.56%,C群抗体阳转率分别为81.21%,98.52%,96.35%和97.70%,其中6～11月龄试验组与对照组A群抗体阳转率差异有统计学意义(χ26～11M=11.554 6,P=0.000 7)其他年龄试验与对照组差异均无统计学意义,试验组均非劣效于对照组。3～5月龄和6～11月龄组加强免疫后,A群和C群阳转率几乎均达100%。结论试验组A群C群脑膜炎球菌结合疫苗在3月龄～5岁易感人群中具有良好的安全性和免疫原性。     

A群C群脑膜炎球菌多糖结合疫苗在已完成基础免疫的18月龄儿童中加强免疫的安全性和免疫原性

目的 评价儿童A群C群脑膜炎球菌多糖结合疫苗(Group A and C meningococcal polysaccharide conjugate vaccine, MPCV-AC)加强免疫的安全性和免疫原性。方法 在前期完成MPCV-AC基础免疫Ⅲ期临床试验的受试者中,选择已于3月龄开始接种3剂MPCV-AC(A组)和已于6-11月龄开始接种2剂MPCV-AC(B组)的儿童,于18月龄时加强接种1剂MPCV-AC,观察接种后0-30d不良反应和6个月内严重不良反应,检测接种前后血清A群和C群脑膜炎奈瑟菌(Neisseria meningitidis, Nm)杀菌抗体,分析不良反应发生率、抗体阳性率和几何平均滴度(Geometric mean titer, GMT)。结果 A组和B组受试者MPCV-AC加强免疫后不良反应发生率分别为22.5%(27/120)、25.8%(31/120),未发生4级不良反应和与疫苗接种有关的严重不良事件。A组受试者加强免疫后vs加强免疫前A群、C群Nm抗体阳性率分别为100%(112/112)vs 19.33%(23/119)、99.11%(111/...     

国产Ⅲ价轮状病毒基因重配株疫苗安全性和免疫原性初步研究

目的：评价国产Ⅲ价轮状病毒基因重配株疫苗在中国健康成人、儿童和婴幼儿中服用的安全性和免疫原性。方法采用随机、双盲和安慰剂对照研究方法,按照1∶1的比例分别给予140名健康观察对象（其中18岁以上40名、6～17岁40名、2～35月龄60名）接种我国某厂家生产的Ⅲ价轮状病毒基因重配株疫苗（简称Ⅲ价RV基因重配疫苗）和安慰剂。观察接种日和接种后28天内的全身反应;采用间接酶联免疫吸附试验方法（ELISA）检测婴幼儿试验对象免疫前后的抗轮状病毒IgA抗体。结果Ⅲ价RV基因重配疫苗与安慰剂全身反应相似,均未见全身严重不良反应。经3剂免疫后特异性抗体滴度均增加,疫苗组为免疫前的3.86倍,安慰剂组为原来的2.46倍,免疫后两组间抗体滴度及增长倍数均无统计学差别（P值均﹥0.05）。结论Ⅲ价RV疫苗在健康人群特别是2～35月龄目标人群中接种的安全性良好并具有一定的免疫原性。     

国产b型流感嗜血杆菌结合疫苗的免疫原性

目的评价国产b型流感嗜血杆菌结合疫苗在3月龄～5岁婴幼儿中的免疫原性。方法将江苏省涟水县3月龄～5岁适宜接种b型流感嗜血杆菌结合疫苗的健康婴幼儿作为观察对象。按0、1、2月的免疫程序,3～5月龄儿接种3剂Hib结合疫苗,并于第3剂接种后1年加强免疫1剂;按0、1月(28 d)的免疫程序,6～11月龄儿接种2剂; 1～5岁婴幼儿接种1剂。3～11月龄儿接种部位为臀部外上方1/4处肌内、1～5岁婴幼儿接种部位为上臂三角肌外侧肌内。分别于受种儿免疫前、3～5月龄儿第3针接种后1月(28 d)及加强免疫后1月(28 d)、6～11月龄儿第2针免疫后1月(28 d)、1～5岁婴幼儿第1针免疫后1月(28 d),采集每个受种儿静脉血,分离血清,ELISA法检测每份血清抗Hib PRP抗体,并计算血清抗Hib PRP抗体的几何平均浓度(GMC)和几何平均浓度增长倍数(GMFI)。结果免疫接种后,各年龄组受种儿血清抗Hib PRP抗体浓度均≥1.0μg/ml,均获得了长期保护水平;1～5岁、6～11月龄、3～5月龄受种儿免疫后Hib抗体GMC分别达到131.22、14.86、15.59μg/ml,GMFI达到42.13、47.61、121.59,均较免疫前大幅升高。3～5月龄儿加强免疫1剂后,血清Hib抗体GMC由15. 19μg/ml升至57.21μg/ml。结论国产b型流感嗜血杆菌结合疫苗免疫3月龄～5岁婴幼儿后,均获得了较好的免疫原性。     

健康人群接种15价肺炎球菌结合疫苗的安全性评估

目的评价国产15价肺炎球菌结合疫苗在中国健康成人、儿童和婴幼儿中接种的安全性。方法 2020年1—8月在河北省疫苗临床研究基地采用单中心、单臂试验设计, 共入组100名2月龄(最小可至6周龄)以上受试者。受试者共分为5个年龄组:≥18岁组、1～5岁组、7～11月龄组、3月龄组和2月龄组(最小可至6周龄), 各年龄组均为20名。≥18岁组和1～5岁组受试者接种1剂试验疫苗, 7～11月龄组以0、2月程序接种2剂试验疫苗, 3月龄组和2月龄组分别按0、1、2月程序和0、2、4月程序接种3剂试验疫苗。采用定期随访和主动报告相结合的方式, 观察疫苗接种后30 d内的不良反应。结果≥18岁组接种1剂后有14例发生不良反应;1～5岁组有10例出现不良反应。7～11月龄组2剂接种后共有11例出现不良反应, 严重程度多为轻度。2～3月龄组人群共有26例发生不良反应, 发生率为65.00%(26/40), 其中3月龄和2月龄发生例数分别为12例与14例;不良反应以全身反应为主, 发热(57.50%, 23/40)和胃肠道反应(腹泻15.00%, 6/40)较多见;以轻至中度为主, 多数发生在接种后7 d...     

4~6岁儿童接种麻疹-流行性腮腺炎-风疹联合减毒活疫苗加强免疫的免疫原性与安全性研究

目的 探讨4~6岁儿童接种麻疹-流行性腮腺炎-风疹联合减毒活疫苗（MMR）后的加强免疫原性与安全性。方法 分别在山西省、内蒙古自治区以及北京市招募曾有8月龄和18月龄接种过1剂麻疹-风疹联合减毒活疫苗和MMR疫苗免疫史的4~6岁儿童作为研究对象,分为4、5、6岁组,进行MMR疫苗加强免疫研究。接种MMR疫苗前与接种后35~42 d各采集血标本3 ml。在研究期间,主动监测疫苗接种后30 min、1 d、2 d、3 d、4~12 d,以及13~42 d的不良事件。血清采用酶标法检测麻疹、流行性腮腺炎和风疹的IgG抗体。采用方差分析或非参数检验比较研究组间麻疹、腮腺炎和风疹抗体几何平均浓度（GMC）,采用χ²检验或Fisher确切概率法比较组间阳性率和不良事件发生率。结果 共500名完成免后采血儿童纳入免疫原性分析,535名儿童纳入安全性分析。总体不良事件发生率为20.37%,轻度不良事件最多。局部与全身不良事件发生率分别为0.37%和20.00%。局部不良事件的症状以接种部位发红为主,全身不良事件以发热症状为主,其次为咳嗽、皮疹、流涕等。在4~6岁进行1剂MMR疫苗加强免疫后,麻疹抗体、腮腺炎抗体与风疹抗体阳性率均在99%以上,3组间阳性率差异无统计学意义。3组间仅腮腺炎抗体GMC差异有统计学意义（P=0.042）,麻疹与风疹抗体相关结果均无差异。免前阴性者的麻疹、腮腺炎及风疹抗体GMC均低于免前阳性者。结论 在4~6岁儿童中进行MMR疫苗的加强免疫,具有良好的免疫原性与安全性,在4~6岁之间的加强免疫效果相近。     

世界卫生组织140个成员国肺炎球菌疫苗常规免疫程序现状分析

目的了解世界卫生组织(WHO)140个成员国肺炎球菌疫苗免疫程序,为优化中国肺炎球菌疫苗免疫策略提供参考依据。方法汇总WHO网站2018年2月28日更新的疫苗可预防疾病监测公开数据,分析WHO 140个成员国肺炎球菌疫苗的种类、常规免疫程序、接种年龄和地区分布。结果 WHO的140个成员国中,有118个(84.3%)国家实施3剂肺炎球菌多糖结合疫苗(PCV)免疫程序,21个(15.0%)国家实施4剂PCV免疫程序,1个(0.7%)国家实施≥5剂PCV免疫程序;PCV为3剂的118个国家中,59个(50.0%)国家在2月龄开始接种,47个(39.8%)国家在1.5月龄开始接种;PCV第2剂和第3剂在全程接种3剂且选择基础免疫3剂和全程接种≥4剂的81个国家中,分别有44个(54.3%)和43个(53.1%)国家在2.5月龄和3.5月龄接种;PCV第2剂和第3剂在全程接种3剂且选择基础免疫2剂加强免疫1剂的59个国家中,分别有40个(67.8%)和39个(66.1%)国家在4月龄和12月龄接种;PCV第4剂接种月龄在接种≥4剂的22个国家中,6个(27.3%)国家在15月龄接种,5个(22.7%)国家在18月龄接种。WHO公布肺炎球菌多糖疫苗(PPV)免疫程序的40个国家中,17个(42.5%)国家在欧洲区(EUR),13个(32.5%)国家在美洲区(AMR),7个(17.5%)国家在西太平洋区(WPR),3个(7.5%)国家在东地中海区(EMR);PPV多推荐接种1剂次,22个(55.0%)国家在≥50岁人群接种。结论 WHO 140个成员国的PCV常规免疫程序根据肺炎发病情况分为基础免疫3剂、基础免疫2剂加强免疫1剂和基础免疫3剂加强1剂,PPV多推荐接种1剂次,中国可根据国内肺炎球菌性疾病的流行水平、特征及疫苗各剂次时间安排等因素确定相应的免疫策略。     

健康幼儿甲型肝炎灭活疫苗加强免疫效果评价

目的 评价甲型肝炎(甲肝)灭活疫苗一针加强免疫程序的免疫效果和安全性,为补充甲肝疫苗免疫预防策略提供依据.方法 选择100名已经完成甲肝减毒疫苗接种6个月以上24 ～ 38月龄儿童,加强接种1剂次甲肝灭活疫苗免后1个月,采用定量微粒子酶联免疫法检测免疫前后甲肝抗体,评价甲肝抗体水平和阳性率.并对受试者进行连续3d的反应观察和随访,以评价其安全性.结果 加强免疫1个月后甲肝抗体阳性率由免疫前的95.2％上升到100％,甲肝抗体水平由免疫前的124.4 mU/ml上升到7 269.3 mU/ml,增长倍数达55.7倍.观察到12例不良反应,均为发热,发生率为5.7％;未发现其他不良反应.结论 甲肝灭活疫苗进行加强免疫具有良好的免疫原性和安全性,建议增加1剂次加强免疫程序,帮助受种者获得长期的甲肝抗体保护.     

甲型肝炎灭活疫苗或甲型乙型肝炎联合疫苗加强免疫的免疫原性和安全性研究

目的在甲肝减毒活疫苗1剂次免疫的基础上,评价甲肝灭活疫苗和甲乙肝联合疫苗加强免疫的安全性和免疫原性,为制定甲肝疫苗的免疫策略提供依据。方法在广东省翁源县选择24～30月龄曾接种过甲肝减毒活疫苗且间隔在6个月以上的健康幼3L262／,~,随机分为2组。136人接种1针甲肝灭活疫苗,126人接种1针甲乙肝联合疫苗。每个受试者接种疫苗前采血3mL,接种疫苗后进行30rain即时留院观察,随后进行3d安全性观察。受试者于接种疫苗后28d采血3mL,采用微粒子酶免法检测免疫前后甲乙肝抗体。结果甲肝灭活疫苗组与甲乙肝联合疫苗组免疫前甲肝抗体浓度分别为124．87、100．82mIU／mL,抗体阳性率分别为96．32％（131／136）和93．65％（118／126）;免疫后2组儿童甲肝抗体浓度分别为5856．79、4514．00mIU／mL,抗体阳性率分别为100．00％（111／111）和99．06％（105／106）,抗体浓度分别增长45．32倍和45．31倍,2组间抗体浓度增长倍数差异均无统计学意义（P〉0．05）,而甲肝灭活疫苗组和甲乙肝联合疫苗组加强免疫前后甲肝抗体浓度差异均有统计学意义（P〈0．01）。本次研究共观察到46例不良反应,均为全身反应,发生率为17．56％（46／262）,其中甲肝灭活疫苗组观察到18例不良反应,发生率为13．24％,甲乙肝联合疫苗组观察到28例不良反应,发生率为22．22％,2组间差异无统计学意义（P〉0．05）。46例不良反应中,1级（轻度）35例,2级（中度）9例,3级（重度）2例反应。结论甲型肝炎灭活疫苗或甲型乙型肝炎联合疫苗加强免疫具有良好的免疫原性和安全性。     

无细胞百白破联合疫苗安全性和免疫原性研究

[目的]评价长春长生生物科技股份有限公司研制的吸附无细胞百白破联合疫苗的安全性和免疫原性。[方法]在江苏省连云港市赣榆县选择3~5月龄、未接种过百白破联合疫苗、无百日咳白喉破伤风疾病史的足月健康儿童进行临床研究,采用随机、双盲、同类疫苗平行对照设计,将观察对象按3︰2的比例随机分别接受观察疫苗和对照疫苗的接种。在观察期内对接种对象进行安全性观察,接种前后采集血清样本,进行免疫原性的观察。[结果]受试者全身中度发热反应发生率为1.62%（15/924）,没有出现全身严重及以上反应。未出现中度以上局部反应。免疫原性结果表明：受试者破伤风抗毒素阳转率为100.00%;白喉抗毒素阳转率为98.05%;抗百日咳毒素抗体阳转率为87.99%,抗丝状血凝素抗体阳转率为93.18%。[结论]该疫苗接种后具有低反应性和较好的免疫原性。     

Safety and immunogenicity of fully liquid DTaP₅-IPV-Hib pediatric combination vaccine (Pediacel®) compared to DTaP₃-HBV-IPV/Hib (Infanrix® Hexa) when coadministered with heptavalent pneumococcal conjugate vaccine (PCV7) as a booster at 11-18 months of age: a phase III, modified double-blind, randomized, controlled, multicenter study

This study compared the safety and immunogenicity of DTaP?-IPV-Hib vaccine (followed by monovalent hepatitis B vaccine [HBV]) and DTaP?-HBV-IPV/Hib vaccines, both coadministered with PCV7, as a fourth-dose booster in toddlers 11-18 months who had a hexavalent vaccine primary series. The fever rate within 4 days of DTaP?-IPV-Hib was noninferior to DTaP?-HBV-IPV/Hib. DTaP?-IPV-Hib induced a marked immune response and had a similar safety and immunogenicity profile compared with DTaP?-HBV-IPV/Hib. Fully liquid DTaP?-IPV-Hib can be used as a booster after a hexavalent vaccine primary series; where required, a fourth dose of monovalent HBV can be administered after DTaP?-IPV-Hib (NCT ID: NCT00355654).     

Safety and immunogenicity of a 7-valent pneumococcal conjugate vaccine (Prevenar): primary dosing series in healthy Chinese infants

This was a randomized safety/immunogenicity evaluation of PCV7 primary series at 3, 4, 5 months in healthy Chinese infants. Eight hundred subjects were randomized to Group 1 (PCV7 > or =7 days before DTaP), or Group 2 (PCV7 with DTaP), or Group 3 (DTaP only). Erythema and induration/swelling were recorded at the PCV7 injection site at any individual dose in no more than 12% and 8% of subjects, respectively, and neither exceeded 2.5 cm in >1% of subjects. Fever >38.0 degrees C was observed in <13% of subjects at any individual dose. For each vaccine serotype, at least 90% of subjects (Groups 1 and 2) had IgG concentrations > or = 0.35 microg/mL after dose 3, except type 6B (Group 2) with 83.3%. PCV7 had an acceptable safety profile and was immunogenic in Chinese infants.     

Immunogenicity, reactogenicity, and safety of a seven-valent pneumococcal conjugate vaccine (PCV7) concurrently administered with a fully liquid DTPa-IPV-HBV-Hib combination vaccine in healthy infants

AIM OF THE STUDY: To evaluate the immunogenicity, safety and reactogenicity of a seven-valent pneumococcal conjugate vaccine (PCV7) when given concomitantly with a fully liquid DTaP-IPV-HBV-Hib combination vaccine. METHODS: Two hundred and sixty-six healthy infants in France (n=136) and Germany (n=130) were randomized to receive DTaP-IPV-HBV-Hib and PCV7 (test group) at the age of 2, 3 and 4 months (primary series) and 12-15 months (booster dose), or to receive DTaP-IPV-HBV-Hib at the same time points but PCV7 at the ages of 5, 6, 7 and 13-16 months (control group). Antibody levels to all vaccine antigens were measured before dose 1, 1 month after dose 3, at the time of booster, and 1 month later. Safety data were collected after each vaccine dose. RESULTS: Two hundred and fifty-seven infants (test group, 131; control group, 126) completed the primary immunization series and two hundred and forty-five received the booster dose (test group, 125; control group, 120). Depending on the serotype, 92.8-100% of subjects in the test group achieved antibody levels >or=0.15 microg/mL for PCV7 antigens at 5 months of age, and 89.7-99.1% of them antibody levels >or=0.50 microg/mL 1 month after booster. For DTaP-IPV-HBV-Hib, there was no statistically significant difference between the two groups in the proportion of infants that achieved pre-defined seroprotective levels for each antigen at 5 months and 1 month after booster. Frequency of local and systemic reactions was similar in both groups except for fever above 38.0 degrees C, which was more frequent in the test group after dose 1, 2 or 4. Fever >39.0 degrees C was only reported from three children in each group. CONCLUSION: The PCV7 vaccine was highly immunogenic, well tolerated, and safe when coadministered with the DTPa-IPV-HBV-Hib vaccine at 2, 3, and 4 months of age and a booster dose at 12-15 months. In this study, PCV7 did not show any relevant influence on the immunogenicity and safety of the concurrently administered DTPa-IPV-HBV-Hib vaccine.     

Safety and immunogenicity of a diphtheria,tetanus, acellular pertussis and Haemophilus influenzae Type b combination vaccine compared with separate administration of licensed equivalent vaccines in Chinese infants and toddlers for primary and booster immunization

To evaluate the safety and immunogenicity of a diphtheria, tetanus, acellular pertussis and Haemophilus infuenzae Type b (DTaP/Hib) combination vaccine first developed by a Chinese manufacturer, a randomized, two-stage, parallel controlled, single center clinical trial was conducted in Dafeng, Jiangsu Province of China. A total of 720 infants were enrolled and randomly assigned to two groups with a 2:1 allocation. In Stage I, 480 subjects in Group T were administered with 3 doses of the DTaP/Hib vaccine at 3, 4 and 5 months of age, respectively, while 240 subjects in Group C received separate licensed DTaP vaccine and Hib conjugate vaccine on the same schedule. In Stage II, 633 primed toddlers (431 of Group T and 202 of Group C) were given a booster dose at 18 months of age. Sera samples were collected at pre-dose 1, 4 weeks post-dose 3, pre-dose 4 and 4 weeks post-dose 4, respectively. Levels of protective antibodies were measured by Enzyme Linked Immunoadsorbent Assay (ELISA). Immunogenicity was evaluated with regard to geometric mean concentrations (GMCs), seroconversion rates and seroprotection rates of the antibodies. Solicited adverse reactions were recorded for 3 days after each dose; unsolicited adverse events and serious adverse events were monitored for 28 days after vaccination. Results showed that seroconversion rates of anti-pertussis toxoid (PT), anti-filamentous hemagglutinin (FHA), anti-diphtheria toxoid (DT), anti-tetanus toxid (TT) and anti-polyribosyl-ribitol-phosphate (PRP) in Group T (Stage I: 98.06%, 97.33%, 100%, 100%, 98.79%; Stage II: 99.18%, 83.42%, 99.18%, 63.32%, 85.05%) were comparable to that of Group C (Stage I: 95.26%, 93.16%, 100%, 100%, 98.42%; Stage II: 98.89%, 83.89%, 98.33%, 53.89%, 76.67%). Nearly 100% of the subjects in both groups achieved seroprotective levels of anti-DT (≥0.1 IU/ml), anti-TT (≥0.1 IU/ml) and anti-PRP (≥0.15 μg/ml) after primary and booster vaccination. The frequencies of local induration, swelling and redness as well as general reactions such as fever, diarrhea and anaphylaxis were low and acceptable in both groups. In conclusion, the DTaP/Hib vaccine was demonstrated to be non-inferior to the control vaccines on safety and immunogenicity. There could be a bright future for the DTaP/Hib vaccine to be widely used in the universal vaccination of Chinese children.     

中国婴幼儿接种吸附无细胞百白破灭活脊髓灰质炎和b型流感嗜血杆菌(结合)联合疫苗的安全性和免疫原性研究

目的 比较吸附无细胞百白破灭活脊髓灰质炎和b型流感嗜血杆菌(结合)联合疫苗(DTaP-IPV//PRP～T联合疫苗)与吸附无细胞百白破联合疫苗(DTaP)、b型流感嗜血杆菌结合疫苗(Hib结合疫苗)、注射用灭活脊髓灰质炎疫苗(IPV)的免疫原性和安全性.方法 受试者随机分为三组.试验组(A组和B组)分别于2、3、4月龄...     

A Phase III randomized,double-blind,clinical trial of an investigational hexavalent vaccine given at 2, 4, and 11–12 months

BackgroundCombination vaccines simplify vaccination visits and improve coverage and timeliness. DTaP5-HB-IPV-Hib is a new investigational, fully-liquid, combination vaccine designed to protect against 6 infectious diseases, including 5 pertussis antigens and OMPC instead of PT as conjugated protein for Hib component.MethodsIn this multicenter, double-blind, comparator-controlled, Phase III study (NCT01480258) conducted in Sweden, Italy, and Finland, healthy infants were randomized 1:1 to receive one two immunization regimens. The DTaP5-HB-IPV-Hib Group received the investigational hexavalent vaccine (DTaP5-HB-IPV-Hib) and the Control Group received Infanrix-hexa (DTPa3-HBV-IPV/Hib) at 2, 4 and 11–12 months of age. Both groups received concomitantly Prevnar 13 (PCV13) and Rotateq (RV5) or Rotarix (RV1) at 2, 4 months of age and PCV13 at 11–12 months. Subjects administered RV5 received a 3rd dose at 5 months of age.ResultsA total of 656 subjects were randomized to the DTaP5-HB-IPV-Hib Group and 659 subjects to Control Group. Immune responses to all vaccine antigens post-toddler dose were non-inferior in the DTaP5-HB-IPV-Hib Group as compared to the Control Group. Additionally, the post-dose 2 and pre-toddler DTaP5-HB-IPV-Hib anti-PRP responses were superior. The DTaP5-HB-IPV-Hib Group responses to concomitant RV1 were non-inferior compared to the Control Group.Solicited adverse event rates after any dose were similar in both groups, except for higher rates of pyrexia (6.4% difference; 95% CI: 1.5, 11.3) and somnolence (5.8% difference; 95% CI: 1.7, 9.8) in the DTaP5-HB-IPV-Hib Group. Vaccine-related serious adverse events occurred infrequently in the DTaP5-HB-IPV-Hib Group (0.3%) and the Control Group (0.5%).ConclusionsThe safety and immunogenicity of DTaP5-HB-IPV-Hib is generally comparable to Control when administered in the 2, 4, 11–12 month schedule. Early Hib responses were superior versus Control. DTaP5-HB-IPV-Hib could provide a new hexavalent option for pediatric combination vaccines, aligned with recommended immunizations in Europe.Study identification: V419-008CLINICALTRIALS.GOV identifier: NCT01480258     

Immunogenicity, reactogenicity and safety of a 7-valent pneumococcal conjugate vaccine (PCV7) concurrently administered with a DTPa-HBV-IPV/Hib combination vaccine in healthy infants

BACKGROUND: To evaluate immunogenicity, reactogenicity, and safety of a hexavalent combination vaccine diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated polio virus-Haemophilus influenzae type b (DTPa-HBV-IPV/Hib) when coadministered with a 7-valent pneumococcal conjugate vaccine (PCV7). METHODS: Infants received either a hexavalent diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated polio virus-H. influenzae type b vaccine concomitantly with PCV7 or DTPa-HBV-IPV/Hib alone infants were vaccinated at 2, 3 and 4 months (primary immunization) and 12-15 months of age (booster dose). Local and systemic reactions and adverse events were monitored following each dose and compared between groups. Blood was obtained prior to dose 1, one month after dose 3, immediately prior to and 1 month following the booster dose to measure antibody responses to each of the antigens. RESULTS: Two hundred and fifty-three subjects (PCV7, 127; Control, 126) were enrolled. Antibody responses were compared in 226 subjects for the primary immunization and 212 for the booster dose (per-protocol (PP) population). Although there were some differences in geometric mean concentrations (GMCs) to the DTPa-HBV-IPV/Hib antigens after the primary series, GMCs for all antigens after the booster dose were similar in both groups, except for diphtheria which was significantly higher in the PCV7 group (PCV7, 7.41 IU/mL; Control, 5.78 IU/mL). Reactogenicity and safety data were compared in 252 infants receiving primary immunization and 235 children receiving the booster dose. Site reactions were similar in both groups. Fever >or=38.0 degrees C following each vaccination was reported more frequently in the PCV7 group (28.3-50.0%) than in the Control group (15.6-33.6%) whereas fever >39.0 degrees C occurred only in a few cases and to the same extent in both groups (PCV7, 0.8-2.7%; Control, 1.6-4.1%). Only one reported serious adverse event was characterized as being related to the study vaccines: control subject was hospitalized with a fever. CONCLUSION: DTPa-HBV-IPV/Hib and PCV7 were highly immunogenic, well-tolerated and safe when coadministered at 2, 3 and 4 months of age with a booster dose at 12-15 months of age. These results support the coadministration of PVC7 with DTPa-HBV-IPV/Hib as part of the routine immunization schedule for infants and children.     

Immunogenicity and reactogenicity of Infanrix™ when co-administered with meningococcal MenACWY-TT conjugate vaccine in toddlers primed with MenHibrix™ and Pediarix™

BackgroundCo-administration of an investigational quadrivalent meningococcal serogroups A, C, W and Y tetanus toxoid conjugate vaccine (MenACWY-TT) with the fourth dose of diphtheria–tetanus–acellular pertussis vaccine (DTaP) at age 15–18 months was investigated in 3-dose Haemophilus influenzae type b-meningococcal serogroups C/Y conjugate vaccine (HibMenCY-TT)-primed toddlers.MethodsInfants were randomized (5:1) and primed at 2, 4 and 6 months of age with HibMenCY-TT and DTaP-hepatitis B-inactivated poliovirus (DTaP-HBV-IPV) vaccine, or Hib-TT and DTaP-HBV-IPV (Control). HibMenCY-TT+ DTaP-HBV-IPV vaccinees were re-randomized (2:2:1) to receive MenACWY-TT at 12–15 months and DTaP at 15–18 months (MenACWY-TT group); MenACWY-TT co-administered with DTaP at 15–18 months (Coad group); or HibMenCY-TT at 12–15 months and DTaP at 15–18 months (HibMenCY-TT group). Controls received DTaP at 15–18 months. Only children in the HibMenCY-TT group received a fourth dose of Hib conjugate vaccine due to Hib conjugate vaccine shortage at the time of the study. DTaP immunogenicity and reactogenicity were assessed one month post-vaccination.ResultsPre-defined statistical non-inferiority criteria between Coad and Control groups were met for diphtheria, tetanus and filamentous haemagglutinin but not pertussis toxoid and pertactin. Following vaccination ≥99% of children had anti-diphtheria/anti-tetanus concentrations ≥1.0 IU/ml. Pertussis GMCs were lower in all investigational groups versus Control. In post hoc analyses, pertussis antibody concentrations were above those in infants following 3-dose DTaP primary vaccination in whom efficacy against pertussis was demonstrated (Schmitt, von König, et al., 1996; Schmitt, Schuind, et al., 1996). The reactogenicity profile of the Coad group was similar to DTaP administered alone.ConclusionRoutine booster DTaP was immunogenic with an acceptable safety profile when co-administered with MenACWY-TT vaccine in HibMenCY-TT-primed toddlers. These data support the administration of a fourth DTaP dose following a 4-dose HibMenCY-TT vaccination series, or co-administered with MenACWY-TT in HibMenCY-TT-primed children.     

Immunogenicity and safety of a booster dose of the 13-valent pneumococcal conjugate vaccine in children primed with the 10-valent or 13-valent pneumococcal conjugate vaccine in the Czech Republic and Slovakia

BackgroundAlthough both the 13-valent pneumococcal conjugate vaccine (PCV13) and the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV) are widely used, it is unclear how interchangeable they are in terms of immunogenicity.MethodsTwo phase 3, open-label, multicenter studies were conducted to assess the immunogenicity and safety of a booster dose of PCV13 in children primed with PHiD-CV or PCV13. In the Czech Republic, 12–15-month-old children received a PCV13 booster after 3-dose priming with either PHiD-CV or PCV13. In Slovakia, 11–12-month-old children received PCV13 following 2-dose priming with either PHiD-CV or PCV13. Serum IgG concentrations were assessed by enzyme-linked immunosorbent assay and functional antibodies were assessed by opsonophagocytic assay (OPA) before the booster and at 1 and 12 months afterward. The primary objective of these studies was to assess non-inferiority of OPA titers for serotype 19A in PHiD-CV-primed subjects compared to those in PCV13-primed children 1 month post-booster.ResultsA total of 98 subjects in the Czech Republic and 89 subjects in Slovakia were included. One month after the PCV13 booster dose, the IgG and OPA immune responses to serotype 19A in subjects primed with 2 or 3 doses of PHiD-CV were non-inferior to those in subjects primed with PCV13. Non-inferior and persistent immune responses to most other vaccine serotypes were also observed after the PCV13 booster in PHiD-CV-primed subjects. No safety issues were raised in either study.ConclusionsOverall, robust IgG and OPA immunological responses were observed after booster vaccination with PCV13 in children primed with 2 or 3 doses of PHiD-CV or PCV13, including for serotypes not included in PHiD-CV. These results suggest that these vaccines are interchangeable in terms of safety and immunogenicity and that PCV13 can be used as a booster in the context of mixed schedules. (EudraCT numbers: 2012-005366-35 and 2012-005367-27).     

Assessment of nine candidate DTP-vaccines with reduced amount of antigen and/or without adjuvant as a fourth (booster-) dose in the second year of life

BACKGROUND: The incidence of local reactions to diphtheria-, tetanus and acellular pertussis (DTaP-) vaccines in infants and toddlers increases with each subsequent dose, and entire thigh swellings (ETS) have been reported. Lowering the amount of antigen or of adjuvant may decrease the reactogenicity of DTaP while maintaining a protective immune response. OBJECTIVES: Following priming with three doses of a DTaP vaccine during infancy, the safety, reactogenicity and immunogenicity of nine different candidate DTaP-vaccines with reduced amounts of antigen and/or adjuvant given as fourth (booster) dose were evaluated. METHODS: Study participants were healthy infants aged 15-27 months at the time of booster vaccination. Each participant had received three doses of a DTaP vaccine (Infanrixtrade mark, GlaxoSmithKline, Rixensart, Belgium; "reference DTaP") at age 3, 4, and 5 months as part of a previous clinical trial. More than 20,000 children were eligible for participation in the current study protocol at the time. In a first phase at a University hospital-based vaccination study center, nine sequential cohorts of 63-119 study subjects received one of nine different candidate vaccines. Patients and study personal were blinded with regard to which vaccine was currently in use. Reactogenicity was solicited from parents using diary cards. Blood was drawn prior to and 4 weeks after vaccination and immediately centrifuged. The serum was stored at -20 degrees C until serology was performed by ELISA tests. As soon as the first candidate vaccine with adequate reactogenicity and immunogenicity profile was identified in the first study phase, a second study phase was initiated in parallel, to evaluate the safety and reactogenicity of the respective candidate vaccine in private practices in large cohorts (1613-2095 study subjects per group). RESULTS: In the first study phase, DTaP with no aluminum induced the highest frequency of ETS and fever. All other candidate vaccines caused lower rates of local and general reactions than the reference DTaP. As a general rule, vaccines with less antigen induced fewer reactions, although there was no strict dose-response effect and the difference, e.g. between a one-tenth and a one-fifth DTaP dose (DTaP 1/5; DTaP 1/10) was not clinically relevant. Separate injections of Td and aP caused fewer general reactions than the respective TdaP combination and local reactions were higher at the aP than at the Td injection site. Again, as a general rule, reduced amounts of antigen induced lower antibody concentrations, although all vaccines induced "protective" anti-tetanus and anti-diphtheria antibody responses. A total of 92-100% of children showed seroresponses to pertussis antigens even when vaccinated with reduced amounts of the respective pertussis antigen. Elimination of aluminum from DTaP vaccine induced higher anti-tetanus-antibody concentrations and so did a reduction of the amount of diphtheria antigen. Additional examples for antigen interaction were increased antibody concentrations, observed with injection of Td and aP into different limbs. In the second study phase, all three vaccines evaluated (one with a reduced amount of diphtheria antigen, TdaP; one with reduced amounts of all antigens, tdap; and one with a fifth dose of the reference vaccine (DTaP 1/5)) were safe and had an acceptable reactogenicity profile in a total of 4871 study subjects. CONCLUSIONS: Local reactions due to DTaP booster doses in the second year of life can be reduced by reducing the amount of antigen in the respective vaccine while an adequate immunogenicity is maintained. Aluminum-free vaccines induced ETS and fever most commonly. Any changes in vaccine composition should lead to a full evaluation of the new product.