河南省驻马店市HlV单阳家庭阴性配偶抗体阳转率及其影响因素研究

目的了解河南省驻马店市HIV单阳家庭阴性配偶抗体阳转率及其影响因素。方法收集分析当地2006-2011年艾滋病综合防治信息系统和HIV单阳家庭随访管理信息系统中HIV单阳家庭随访信息,每6个月随访一次,包括HIV单阳家庭阴性配偶的人口学信息、原阳性配偶感染特征和抗病毒治疗情况,以及夫妻间性行为特征和社会支持情况,并检测阴性配偶的HIV血清阳转情况。采用Cox比例风险模型分析HIV单阳家庭阴性配偶抗体阳转的影响因素。结果4813户HIV单阳家庭中,127例阴性配偶发生HIV抗体阳转,2006-2011年总HIV抗体阳转率为0.63/100人年,各年抗体阳转率为0.29/100人年~1.28/100人年,维持在1%左右。HIV阴性配偶受教育程度为初中以下(RR=1.50,95%C1:1.02~2.21,P=0.04)、原阳性配偶为未接受抗病毒治疗(RR=3.16, 95%CI: 2.20~4.56,P<0.01)和最近一次CD₄⁺淋巴细胞检测结果<200 cel即1(RR=2.11, 95%C1:1.40~3.19, P<0.01)、最近半年夫妻性生活中性行为频率≥4次/月(RR=4.27, 95%CI: 2.89-6.30, P<0.01)和从不使用安全套(RR=6.40, 95%CI: 3.67-11.17, P<0.01)以及最近半年家庭未获得过经济支持和关怀救助(RR=4.75, 95%CI: 2.34 - 9.64, P<0.01)均是阴性配偶HIV抗体阳转的影响因素。结论近年来驻马店市HIV单阳家庭阴性配偶抗体阳转率趋于稳定,并较之前水平有所下降。随访中需加强感染者抗病毒治疗和依从性管理及夫妻性行为干预,宣传正确的安全套使用知识及搭建社会支持平台。     

新型冠状病毒灭活疫苗不同接种间隔的免疫原性和安全性研究

目的 比较公安人员按不同方案（0~14 d、0~21 d、0~28 d）接种新型冠状病毒（新冠病毒）灭活疫苗的免疫原性和安全性。方法 于2021年1-2月以山西省太原市405名公安人员为研究对象,通过随机分组将其分为3组,分别按照0~14 d、0~21 d和0~28 d方案接种2剂新冠病毒灭活疫苗,采用RT-PCR检测新冠病毒核酸,活病毒微量病变法检测新冠病毒中和抗体,分析3组的新冠病毒中和抗体GMT、血清阳转率和安全性。结果 0~14 d、0~21 d和0~28 d方案组新冠病毒中和抗体血清学阳转率均为100%,其中0~21 d组[166.70（95%CI：148.30~185.10）]和0~28 d组[179.50（95%CI：156.50~202.60）]新冠病毒中和抗体水平接近（P>0.05）,均明显高于0~14 d组[86.08（95%CI：72.36~99.80）]（P<0.001）。3个方案组不良反应发生率分别为1.48%（2/135）、0.74%（1/136）和1.49%（2/134）（P=0.750）,均为轻度不良反应。结论 公安人员按不同方案（0~14 d、0~21 d、0~28 d）接种新冠病毒灭活疫苗后均表现出较好的血清阳转率和安全性,0~21 d和0~28 d接种方案组新冠病毒中和抗体GMT高于0~14 d方案组。     

肠道病毒71型疫苗上市后疫苗保护效果和免疫原性分析

目的 分析肠道病毒71型（EV-A71）疫苗上市接种后的疫苗保护效果和免疫原性。方法 采用队列研究于2017年10－12月在上海市静安区招募符合纳入标准的预防接种门诊受种者为研究对象,按0、30 d程序接种疫苗者纳入接种组,不接种疫苗者纳入对照组,随访观察1年,评估疫苗保护效果和接种2剂次疫苗后抗体水平及阳转率。结果 共纳入3 018名8~20月龄的儿童,接种组1 211人,对照组1 807人,经过1年随访,EV-A71疫苗对EV-A71感染引起的手足口病保护率为100.00%（95% CI：-66.99%~100.00%）。接种组中124人检测了中和抗体,接种首剂疫苗后60 d抗体几何平均滴度（GMT）为41.76（95% CI：35.60~49.34）,接种后365 d GMT为28.44（95% CI：23.59~34.54）。结论 EV-A71疫苗对于儿童有良好的免疫应答,EV-A71感染引起的手足口病病例较少,需进一步观察。     

中国2004－2016年冬季低温与流感发病的相关性研究

目的 探讨中国31个省份冬季低温与流感发病之间的关联性。方法 收集31个省份2004年1月至2016年12月流感的发病数据和气象数据。运用分布滞后非线性模型，控制长期趋势、"星期几效应"等的影响，分析低温与流感发病的相关性。结果 全国流感发病率从2004年的4/10万增加到2016年的22/10万，整体呈现增高的趋势，黑龙江、辽宁、吉林等省份历年的发病率均<5/10万，处于较低的发病水平，而甘肃、河北、广东、北京等省份的流感发病率较高，部分年份的发病率>30/10万。在1-6月，随着气温的升高，流感的发病呈现逐渐降低的趋势，而在7-12月随着气温的降低，流感的发病呈现逐渐升高的趋势。低温对流感发病影响最高的省份，冬季前期是北京（RR=2.90，95%CI：2.57~3.28），冬季后期是西藏（RR=3.37，95%CI：2.03~5.58）；低温对流感发病影响最高的区域，冬季前期是东北地区（RR=2.04，95%CI：1.48~2.79），冬季后期是华南地区（RR=1.77，95%CI：1.61~1.94）。冬季前期和冬季后期低温对流感发病的影响存在地区差异。结论 冬季低温与流感发病之间存在关联性，冬季前期和后期低温对流感发病的影响存在地区差异。     

四价流感病毒裂解疫苗安全性和免疫原性评价

目的评价某公司生产的四价流感病毒裂解疫苗(四价流感疫苗)安全性和免疫原性。方法选择河南省舞阳县和西平县≥3岁的健康人群为研究对象,按照1∶1∶1随机纳入试验组、对照1组和对照2组,分别接种四价流感疫苗、三价流感疫苗(不含Bv型)和三价流感疫苗(不含By型);检测接种前后血凝抑制(HI)抗体滴度,分析接种后疑似预防接种异常反应(AEFI)发生率、HI抗体阳转率、HI抗体保护率和几何平均滴度(GMT)增长倍数,并与欧盟和美国食品药品管理局(FDA)制定的流感疫苗质量标准(HI抗体阳转率40%、HI抗体保护率70%和HI抗体GMT增长倍数2.5)比较。结果纳入2 924人,其中试验组975人,对照1组974人,对照2组975人。接种后30 min～8 d,试验组AEFI发生率为11.7%,高于对照1组的7.9%和对照2组的8.8%(P0.05)。试验组H1N1型、H3N2型、By型和Bv型HI抗体阳转率分别为78.5%、53.3%、78.3%和62.9%,试验组与对照2组By型HI抗体阳转率的率差为42.1%(95%CI:38.0%～46.2%),与对照1组Bv型HI抗体阳转率的率差为33.2%(95%CI:28.9%～37.5%),95%CI的下限均-0.10。试验组、对照1组和对照2组各型HI抗体GMT增长倍数均≥2.5。试验组H1N1型、H3N2型、By型和Bv型HI抗体保护率分别为87.7%、98.7%、93.6%和77.2%,其中By型HI抗体保护率高于对照2组的71.1%(P0.05),Bv型HI抗体保护率高于对照1组的51.0%(P0.05)。结论接种某公司四价流感疫苗后,H1N1型、H3N2型、By型和Bv型的HI抗体阳转率、HI抗体保护率和GMT增长倍数均达到欧盟和FDA制定的流感疫苗质量标准,该四价流感疫苗的安全性和免疫原性与同公司的三价流感疫苗(包括不含Bv型、不含By型)处于同一水平。     

上海市2014-2020年流感发病强度的变化情况

目的 评估上海市2014-2020年流感监测网络的运行情况以及流感发病强度的变化。方法 基于上海市2014年1月1日至2020年12月31日的流感监测数据,对哨点医院流感样病例(ILI)缺报漏报和ILI标本采集情况进行评价,计算ILI就诊百分比(ILI%)、流感病毒检出阳性率和流感发病率,利用季节性自回归移动平均模型构建"反事实"情况下2020年流感发病强度的基线,以定量估计上海市2020年流感发病强度的相对变化。结果 2020年上海市ILI缺报漏报情况评价得分和ILI标本采集情况评价得分<5分的医院占比分别为9.68%和21.05%。上海市2014-2019年和2020年的ILI%分别为1.51%(95%CI:1.50%~1.51%)和2.31%(95%CI:2.30%~2.32%),流感病毒检出阳性率分别为24.27%(95%CI:24.02%~24.51%)和7.15%(95%CI:6.78%~7.54%),流感发病率分别为3.66‰(95%CI:3.62‰~3.70‰)和1.65‰(95%CI:1.57‰~1.74‰)。上海市2020年的ILI%升高了45.25%,流感病毒检出阳性率和流感发病率分别降低了78.45%和51.80%。结论 2020年上海市流感监测网络的运行情况发生改变,ILI%有所升高,流感病毒检出阳性率和流感发病率均有所降低,流感监测质量的改变是一个潜在的影响因素,未来仍需进一步加强流感监测的质量控制。     

中国10省(市)流感成年人住院病例的临床特征及重症危险因素分析

目的 了解中国10省(市)严重急性呼吸道感染(SARI)住院病例哨点监测纳入的流感成年人住院病例的临床特征及重症危险因素。方法 对2009年12月至2014年6月中国10省(市)SARI哨点监测医院纳入的符合SARI定义的≥15岁病例进行流行病学和临床信息调查,采集呼吸道标本进行流感病毒核酸检测。按检测结果将病例分为流感住院组和非流感住院组,分析两组人口统计学信息、临床和流行病学特征,并分析重症危险因素。结果 10家哨点医院共纳入3 071例SARI成年人病例,其中实验室确诊240例(7.8%),以A(H1N1)pdm2009和A(H3N2)亚型流感病毒为主。病例年龄M为63岁,≥65岁老年人占47.1%。144例(60.0%)患有至少1种慢性基础性疾病,流感病例肺气肿比例(7.9%)高于非流感病例(3.8%),差异有统计学意义(χ²=3.963,P=0.047)。19.4%的流感育龄妇女为孕妇,240例流感病例中仅有1.1%在过去一年接种过流感疫苗。流感住院病例中咽痛、呼吸困难所占比例高于非流感住院病例。17.5%的流感病例收入重症监护室治疗,与非流感住院病例间的差异无统计学意义(P=0.160)。23.1%的流感病例在发病后使用了抗病毒药物治疗,高于非流感住院组(4.8%),差异有统计学意义(P<0.001)。流感住院病例中41.5%出现并发症,病毒性肺炎比例明显高于非流感组(P<0.001)。危险因素分析显示,发病入院时间>7 d(RR=1.673,95%CI:1.071～2.614)、患有哮喘(RR=15.200,95%CI:1.157～199.633)、免疫抑制疾病(RR=5.250,95%CI:1.255～21.960)、怀孕(RR=21.000,95%CI:1.734～254.275)是流感重症的危险因素。结论 成年人流感住院病例主要集中在≥65岁组,流感疫苗接种率极低、抗病毒药物使用不足,应推荐孕妇、老年人、慢性病病例等高危人群每年进行流感疫苗预防接种,流感住院病例应及早应用抗病毒药物。     

昼夜温差和相对湿度与汕头市居民急性心肌梗死之间的关联性分析

目的 分析汕头市气象条件对急性心肌梗死（AMI）患者死亡的影响和人群易感性，为当地医疗卫生系统提供防治AMI的科学依据。方法 收集2015年1月1日至2020年12月31日汕头市居民死因监测数据库中因AMI死亡的人群数据，利用分布滞后非线性模型分析昼夜温差和相对湿度对AMI死亡的影响及滞后效应。结果 研究期间汕头市因AMI死亡13 932人，男女性别比为1.3∶1，高昼夜温差暴露和低相对湿度暴露与AMI死亡之间存在显著关联，单日滞后效应均在滞后2 d时出现并达到最大（RR=1.019，95%CI：1.000~1.039；RR=1.018，95%CI：1.003~1.034）；累计滞后效应均在滞后0~14 d时达到最大（RR=1.199，95%CI：1.025~1.401；RR=1.279，95%CI：1.117~1.465）。≥75岁老年人和女性是高昼夜温差暴露和低相对湿度暴露条件下的易感人群。结论 昼夜温差和相对湿度与汕头市AMI死亡之间存在显著关联，其影响有明显的滞后性。女性和≥75岁老年人均为高昼夜温差和低相对湿度暴露条件下的易感人群。     

3~11岁儿童接种新型冠状病毒灭活疫苗的免疫原性研究

目的 评价3~11岁儿童完成新型冠状病毒（新冠病毒）疫苗基础免疫28~42 d后对原始株的免疫原性及与新冠病毒变异株的交叉免疫反应。方法 于2022年1-7月在山东省乳山市招募3~11岁已按照（0,28）d免疫程序完成2剂新冠病毒灭活疫苗基础免疫的受试者,基础免疫后28~42 d采集静脉血3 ml,检测原始株、Beta、Gamma和Delta变异株的中和抗体水平,计算中和抗体阳性率和GMT。结果 纳入免疫原性分析共395人,其中3~5岁组212人,6~11岁组183人。受试者完成基础免疫后28~42 d,血清中对原始株、Beta、Gamma和Delta变异株的中和抗体阳性率分别为100.00%、74.68%、99.24%和97.22%,年龄组间差异无统计学意义（P>0.05）。受试者完成基础疫苗后28~42 d,血清中对原始株、Beta、Gamma和Delta变异株的中和抗体GMT分别为168.19、10.51、53.65和31.10,年龄组间差异无统计学意义（P>0.05）。结论 在3~11岁儿童中接种2剂新冠病毒灭活疫苗的免疫原性良好,可对新冠病毒变异株产生一定的交叉保护。     

抗病毒治疗对广西壮族自治区HIV单阳家庭阴性配偶抗体阳转的预防效果

目的 了解抗病毒治疗(ART)对HIV单阳家庭阴性配偶抗体阳转的预防效果。方法 以2008年1月1日至2014年12月31日广西壮族自治区(广西)所有上报到艾滋病综合防治数据信息管理系统的HIV单阳家庭为研究对象,采用时间相依协变量Cox模型分析ART对阴性配偶HIV抗体阳转的预防效果。结果 共纳入7 694个HIV单阳家庭,其中394个家庭的阴性配偶发生HIV抗体阳转。总HIV抗体阳转率为2.5/100人年(95%CI:2.2/100人年～2.7/100人年),其中未治疗队列阳转率为4.3/100人年(95%CI:3.7/100人年～4.8/100人年),治疗队列阳转率为1.6/100人年(95%CI:1.4/100人年～1.9/100人年)。ART对HIV单阳配偶抗体阳转的预防效果为51%(HR=0.49,95%CI:0.40～0.60),调整性别、年龄、文化程度、婚姻状况、职业、感染途径、基线CD₄⁺T淋巴细胞后预防效果为45%(AHR=0.55,95%CI:0.43～0.69)。ART对年龄≥25岁、初中及以下学历、已婚、农民、基线CD₄⁺T淋巴细胞<500 cells/mm³、通过异性途径感染的先证者阴性配偶血清抗体阳转的预防效果有统计学意义。结论 ART作为广西HIV单阳家庭的一项干预措施是可行且有效的,扩大HIV单阳家庭ART的覆盖面有利于降低HIV夫妻间的传播。     

Comparison of the immunogenicity and safety of quadrivalent and tetravalent influenza vaccines in children and adolescents

BackgroundChildren and adolescents are susceptible to influenza. Vaccination is the most important strategy for preventing influenza, yet there are few studies on the immunogenicity and safety of quadrivalent inactivated influenza vaccine (QIV) containing two A strains (H1N1 and H3N2) and two B lineages (Victoria and Yamagata). Therefore, to further clarify the immunogenicity and safety of QIV in children and adolescents, a meta-analysis was performed to provide a reference for the development of influenza prevention strategies.MethodsPubMed, EMBASE and Cochrane Library were searched for articles published as of February 12, 2019. Random clinical trials comparing the immunogenicity and safety of QIV and TIV among children and adolescents were selected. The main outcomes were comparisons of immunogenicity (seroprotection rate [SPR] and seroconversion rate [SCR] and adverse events using risk ratios (RRs). The meta-analysis was performed using random-effects models.ResultsAmong the 6 months up to 3 years group, QIV showed a higher SPR for B lineages than for TIV-B/Yamagata, with pooled RRs of 3.07 (95% CI: 2.58–3.66) and 1.06 (95% CI: 1.01–1.11), respectively. For the 3 years through 18 years, QIV had a higher SCR and SPR for the Yamagata lineage than for TIV-B/Victoria, with pooled RRs of 2.30 (95% CI: 1.83–2.88) and 1.16 (95% CI: 1.03–1.30), respectively. Compared to TIV-B/Yamagata, a higher SCR and SPR for the Victoria lineage was found for QIV, with RRs of 3.09 (95% CI: 1.99–4.78) and 1.72 (95% CI: 1.22–2.41), respectively. Regarding adverse events, only pain was more frequently reported for QIV than TIV ; the RR was 1.09 (95% CI: 1.02–1.17).ConclusionsThe immunogenicity of QIV for common ingredients was similar to that of TIV, but the former exhibited significantly higher immunogenicity for the unique lineage. QIV also had the same reliable safety as TIV.     

18岁以上人群接种四价流感病毒灭活疫苗免疫原性和安全性的Meta分析

目的 评价18岁以上人群接种四价流感病毒灭活疫苗(QIV)免疫原性和安全性.方法 检索美国国家医学图书馆数据库、Cochrane协作网图书馆、中国生物医学文献数据库、中国期刊全文数据库和万方全文数据库,将有关比较18岁以上人群接种QIV和三价流感病毒灭活疫苗(TIV)免疫原性和安全性的随机对照试验纳入分析.以接种疫苗21 d后产生的针对H1N1、H3N2、B/Victoria、B/Yamagata四个疫苗株的抗体保护率(SPR)和抗体阳转率(SCR)以及不良反应发生率作为结局指标,合并组间的SPR、SCR和不良反应发生率的相对危险度(RR).结果 共纳入5篇文献.针对B/Yamagata的SPR的RR是1.12(95％ CI:1.02～1.22),SCR的RR是2.11(95％ CI:1.51～2.95).针对B/Victoria的SPR的RR是1.14(95％ CI:1.03～1.25),SCR的RR是1.78(95％ CI:1.24～2.55).接种QIV和TIV(含B/Yamagata)后接种部位疼痛发生率的RR是1.23 (95％ CI:1.05～1.44).结论 18岁以上成人接种QIV不仅可以产生与TIV相似的免疫效果和安全性,而且可以对TIV未包含的乙型流感疫苗株产生较好免疫效果.     

Immunogenicity and safety of inactivated quadrivalent influenza vaccine in adults: A systematic review and meta-analysis of randomised controlled trials

BackgroundA quadrivalent influenza vaccine (QIV) includes two A strains (A/H1N1, A/H3N2) and two B lineages (B/Victoria, B/Yamagata). The presence of both B lineages eliminate potential B lineage mismatch of trivalent influenza vaccine (TIV) with the circulating strain.MethodsElectronic database searches of Medline, Embase, Cochrane Central Register of Controlled Trials (CCRCT), Scopus and Web of Science were conducted for articles published until June 30, 2015 inclusive. Articles were limited to randomised controlled trials (RCTs) in adults using inactivated intramuscular vaccine and published in English language only. Summary estimates of immunogenicity (by seroprotection and seroconversion rates) and adverse events outcomes were compared between QIV and TIV, using a risk ratio (RR). Studies were pooled using inverse variance weights with a random effect model and the I² statistic was used to estimate heterogeneity.ResultsA total of five RCTs were included in the meta-analysis. For immunogenicity outcomes, QIV had similar efficacy for the three common strains; A/H1N1, A/H3N2 and the B lineage included in the TIV. QIV also showed superior efficacy for the B lineage not included in the TIV; pooled seroprotection RR of 1.14 (95%CI: 1.03–1.25, p = 0.008) and seroconversion RR of 1.78 (95%CI: 1.24–2.55, p = 0.002) for B/Victoria, and pooled seroprotection RR of 1.12 (95%CI: 1.02–1.22, p = 0.01) and seroconversion RR of 2.11 (95%CI: 1.51–2.95, p < 0.001) for B/Yamagata, respectively. No significant differences were found between QIV and TIV for aggregated local and systemic adverse events within 7 days post-vaccination. There were no vaccine-related serious adverse events reported for either QIV or TIV. Compared to TIV, injection-site pain was more common for QIV, with a pooled RR of 1.18 (95%CI: 1.03–1.35, p = 0.02).ConclusionIn adults, inactivated QIV was as immunogenic as seasonal TIV, with equivalent efficacy against the shared three strains included in TIV, and a superior immunogenicity against the non-TIV B lineage.     

Immunogenicity,reactogenicity, and safety of inactivated quadrivalent influenza vaccine candidate versus inactivated trivalent influenza vaccine in healthy adults aged ≥18 years: A phase III,randomized trial

Background

Two influenza B lineages have been co-circulating since the 1980s, and because inactivated trivalent influenza vaccine (TIV) contains only one B strain, it provides little/no protection against the alternate B-lineage. We assessed a candidate inactivated quadrivalent influenza vaccine (QIV) containing both B lineages versus TIV in healthy adults.

Methods

Subjects received one dose of QIV (lot 1, 2, or 3) or one of two TIVs (B strain from Victoria or Yamagata lineage); randomization was 2:2:2:1:1. Hemagglutination-inhibition assays were performed 21-days post-vaccination; superiority of QIV versus TIV for the alternate B-lineage was demonstrated if the 95% confidence interval (CI) lower limit for the GMT ratio was ≥1.5, and non-inferiority against the shared strains was demonstrated if the 95% CI upper limit for the GMT ratio was ≤1.5. Reactogenicity and safety were assessed during the post-vaccination period. NCT01196975.

Results

Immunogenicity of QIV lots was consistent, QIV was superior to TIV for the alternate B-lineage strain, and QIV was non-inferior versus TIVs for shared strains (A/H1N1, A/H3N2, B-strain). Reactogenicity and safety profile of the QIV was consistent with seasonal influenza vaccines.

Conclusion

QIV provided superior immunogenicity for the added B strain without affecting the antibody response to the TIV strains, and without compromising safety.     

A Phase III randomised trial of the immunogenicity and safety of quadrivalent versus trivalent inactivated subunit influenza vaccine in adult and elderly subjects,assessing both anti-haemagglutinin and virus neutralisation antibody responses

BackgroundTrivalent influenza vaccines (TIVs) offer substantial protection against matching B-strains, however, protection against alternate-lineage B-strains may be enhanced by adding a second B-strain in quadrivalent influenza vaccines (QIVs). In this Phase III, double-blind, multicentre, randomised study, the immunogenicity and safety of subunit inactivated QIV versus TIV was assessed in adult (aged ≥18 to ≤60 years) and elderly (aged ≥61 years) subjects by analysing a combination of haemagglutinin inhibition (HI) and virus neutralisation (VN).MethodsSubjects (n = 1980) were recruited off season (2015/2016) from 20 centres in five European countries and randomised to receive either QIV (n = 1538), TIV with B-strain of the Victoria lineage (n = 221) or TIV with B-strain of the Yamagata lineage (n = 221). The primary aim was to demonstrate non-inferiority of QIV to TIV for immunogenicity against matched influenza strains based on post-vaccination HI titres. Secondary aims were to show superiority of QIV to TIV for immunogenicity against alternate-lineage B-strains and to characterise the immune response by reverse cumulative distribution (RCD) curves of antibody titres and derived serological parameters for HI and VN. Reactogenicity and occurrence of adverse events were assessed post-vaccination.ResultsQIV elicited a non-inferior immune response for matched strains (upper limit of 95% CI for HI geometric mean ratios [GMRs] <1.5) and a superior response for alternate-lineage B-strains (HI GMRs < 1; p < 0.0001) versus TIV. RCD curves demonstrated that post-vaccination HI and VN titres were higher for QIV versus TIV for both alternate-lineage B-strains. Seroconversion rates and geometric mean fold increases of the VN assay were consistent with the HI assay for all strains in QIV. Reporting rates of local and systemic reactions were similar in both vaccine groups.ConclusionsQIV was non-inferior in immunogenicity to TIV for matched strains and superior to the alternate-lineage B-strains in TIV. Safety and tolerability profiles of QIV and TIV were comparable.     

Safety and immunogenicity of a quadrivalent inactivated influenza vaccine compared to licensed trivalent inactivated influenza vaccines in adults

Purpose

To evaluate the safety and immunogenicity of a prototype quadrivalent inactivated influenza vaccine (QIV) containing two influenza B strains, one of each lineage, compared with licensed trivalent inactivated influenza vaccines (TIVs) containing either a Victoria B-lineage strain (2009–2010 TIV) or a Yamagata B-lineage strain (2008–2009 TIV).

Methods

Healthy adults ≥18 years of age were eligible to participate in this phase II, open-label, randomized, controlled, multicenter study conducted in the US. Participants received a single dose of 2009–2010 TIV, 2008–2009 TIV, or QIV. Sera were collected before and 21 days after vaccine administration to test for hemagglutination inhibition (HAI) antibodies to each of the four influenza strains. Immunogenicity endpoints included geometric mean HAI antibody titers (GMTs) and rates of seroprotection (titer ≥1:40) and seroconversion (4-fold rise pre- to post-vaccination). Safety endpoints included frequency of solicited injection-site and systemic reactions occurring within 3 days of vaccination, and unsolicited non-serious adverse events (AEs) and serious AEs (SAEs) within 21 days of vaccination.

Results

One hundred and ninety participants were enrolled to each vaccine group. QIV induced GMTs to each A and B strain that were noninferior to those induced by the 2009–2010 and 2008–2009 TIVs (i.e., lower limit of the two-sided 95% confidence interval of the ratio of GMT_QIV/GMT_TIV > 0.66 for each strain). Rates of seroprotection and seroconversion were similar in all groups. Incidence and severity of solicited injection-site and systemic reactions, AEs, and SAEs were similar among groups.

Conclusion

QIV, containing two B strains (one from each B lineage), was as safe and immunogenic as licensed TIV. QIV has the potential to be a useful alternative to TIV and offer protection against both B lineages.     

Safety and immunogenicity of a seasonal quadrivalent influenza vaccine (GC3110A) in healthy participants aged ≥ 65 years

BackgroundSeasonal Influenza is still considered associated with seasonal morbidity and hospitalization in the elderly population. The World Health Organization (WHO) recommended seasonal quadrivalent influenza vaccine (QIV) to reduce burden of two currently circulating influenza B lineages. Until 2019 Korean National Immunization Program (NIP) recommended trivalent influenza vaccine (TIV) after ongoing debates on cost effectiveness of QIV for elderly population. Although influenza vaccine only showed modest effect on reducing influenza in elderly, this study aimed to evaluate the immunogenicity and safety of inactivated QIV in healthy participants ≥ 65 years of age.MethodsA total of 274 healthy participants aged ≥ 65 years received a QIV. Seroconversion-based vaccine efficacy of 4 strains of seasonal influenza was assessed 21 days after vaccination and adverse events were monitored until 180 days after vaccination.ResultsThe percentages of participants seroconverted after vaccination on HI antibody against each strain were 36.5% (99/271) to A/H1N1, 47.6% (129/271) to A/H3N2, 40.6% (110/271) to B Yamagata, and 49.1% (133/271) to B Victoria. The percentages of participants seroprotected after vaccination on HI antibody against each strain were 81.2% (220/271) to A/H1N1, 98.5% (267/271) to A/H3N2, 95.2% (258/271) to B Yamagata, and 93.7% (254/271) to B Victoria. There was no serious adverse event (SAE) related with the study vaccine.ConclusionThe quadrivalent split influenza vaccine is expected to offer seroprotection against influenza A and both influenza B lineages even in the elderly population.     

Public health impact of including two lineages of influenza B in a quadrivalent seasonal influenza vaccine

The annual trivalent influenza vaccine (TIV) includes viruses representing three influenza strains - one A/H1N1, one A/H3N2, and one B, although two antigenically distinct lineages of influenza B (Victoria and Yamagata) co-circulate annually in the United States. Predicting which lineage of influenza B will predominate during a season is challenging, and cross-protection by immunization against the other lineage is expected to be low. One proposed alternative is to produce a quadrivalent influenza vaccine (QIV) including an influenza B virus from each of the two circulating lineages. We estimated the additional public health benefit of QIV compared with TIV by calculating the expected impact on influenza-related health outcomes (illness, hospitalization, and death) over ten influenza seasons (1999/2000-2008/2009). We included data on the annual incidence of influenza-associated outcomes, virologic circulation, vaccine coverage, and vaccine effectiveness. We also considered annual vaccine production capacity, since available resources would have produced four vaccine viruses instead of three, potentially resulting in fewer doses of QIV. Use of QIV could have reduced annual cases (range: 2200-970,000), hospitalizations (range: 14-8200), and deaths (range: 1-485) in the US. During earlier seasons, adjusting production capacity for a fourth virus in QIV could have resulted in reduced overall influenza vaccine availability and net increases in influenza-associated outcomes. However, in recent seasons, the expected supply of QIV is likely to exceed the doses of vaccine actually administered. The potential net impact of QIV on influenza-associated outcomes is expected to vary between seasons, depending on annual variability in the incidence of influenza caused by the two influenza B lineages, vaccine coverage, and effectiveness. The additional protection provided by including a second lineage of influenza B could result in a modest reduction in influenza-associated outcomes.     

Lineage-matched versus mismatched influenza B vaccine effectiveness following seasons of marginal influenza B circulation

BackgroundSeveral countries have recently transitioned from the trivalent inactivated influenza vaccine (TIV) to the quadrivalent inactivated influenza vaccine (QIV) in order to outweigh influenza B vaccine-mismatch. However, few studies thus far evaluated its benefits versus the TIV in a systematic manner. Our objective was to compare the QIV VE with lineage-mismatched TIV VE.MethodsWe estimated the 2015–2016, 2017–2018, 2019–2020 end-of season influenza B VE against laboratory-confirmed influenza-like illness (ILI) among community patients, using the test-negative design. VE was estimated for pre-determined age groups and for moving age intervals of 15 years.ResultsSince 2011–2012 season, alternate seasons in Israel were dominated by influenza B circulation. Compared with the lineage-mismatched TIV used during the 2015–2016 and 2017–2018 seasons, the 2019–2020 QIV showed the highest all-ages VE, with VE estimates of 56.9 (95% CI 30.1 to 73.4), 16.5 (95% CI –22.5 to 43.1) and ?25.8 (95% CI ?85.3 to 14.6) for the 2019–2020, 2017–2018 and 2015–2016 seasons, respectively. The 2019–2020 VE point estimated were the highest for the 0.5–4, 5–17 and 18–44 years age groups and for more 15-year age intervals as compared to the other seasons.ConclusionsOur results support the rapid transition from the TIV to the QIV.     

Systematic Review on the Cost-Effectiveness of Seasonal Influenza Vaccines in Older Adults

ObjectivesOlder adults are at high risk of influenza-related complications or hospitalization. The purpose of this systematic review is to assess the relative cost-effectiveness of all influenza vaccine options for older adults.MethodsThis systematic review identified economic evaluation studies assessing the cost-effectiveness of influenza vaccines in adults ≥65 years of age from 5 literature databases. Two reviewers independently selected, extracted, and appraised relevant studies using the JBI Critical Appraisal Checklist for Economic Evaluations and Heyland’s generalizability checklist. Costs were converted to 2019 Canadian dollars and adjusted for inflation and purchasing power parity.ResultsA total of 27 studies were included. There were 18 comparisons of quadrivalent inactivated vaccine (QIV) versus trivalent inactivated vaccine (TIV): 5 showed QIV dominated TIV (ie, lower costs and higher health benefit), and 13 showed the results depended on willingness to pay (WTP). There were 9 comparisons of high-dose TIV (TIV-HD) versus TIV: 5 showed TIV-HD dominated TIV, and 4 showed the results depended on WTP. There were 8 comparisons of adjuvanted TIV (TIV-ADJ) versus TIV: 4 showed TIV-ADJ dominated TIV, and 4 showed the results depended on WTP. There were few pairwise comparisons among QIV, TIV-HD, and TIV-ADJ.ConclusionsThe evidence suggests QIV, TIV-HD, and TIV-ADJ are cost-effective against TIV for a WTP threshold of $50 000 per quality-adjusted life-year. Future studies should include new and existing vaccine options for broad age ranges and use more robust methodologies—such as real-world evaluations or modeling studies accounting for methodological, structural, and parameter uncertainty.