流行性感冒亚单位疫苗(类病毒体)临床安全性和免疫原性研究

目的评价流行性感冒(流感)亚单位疫苗(类病毒体)的临床安全性和免疫原性。方法按随机、对照、盲法的原则,以进口同类疫苗为对照开展现场临床试验,比较两种流感疫苗免疫后临床反应率、抗体阳转率、保护率和几何平均滴度(GMT)增长倍数。结果试验组全身反应率(2.8%)和局部反应率(2.4%)与对照组比较,差异无显著的统计学意义。试验组和对照组免疫后H1N1、H3N2、B(亚)型抗体阳转率分别为69.93%、58.04%、63.87%和74.02%、53.92%、75.98%;试验组和对照组H1N1、H3N2、B(亚)型抗体GMT增长倍数分别为7.1、4.5、5.8倍和8.8、4.1、7.8倍,两组间除B(亚)型外,H1N1、H3N2抗体阳转率和GMT增长倍数差异无显著的统计学意义。试验组H1N1、H3N2、B(亚)型抗体保护率为95.86%、92.09%、77.06%,对照组为97.33%、97.02%、82.67%,两组间差异无显著的统计学意义。结论试验组流感亚单位疫苗(类病毒体)接种后的全身反应和局部反应与进口同类疫苗无差异,临床安全性良好;免疫后各型抗体阳转率、保护率较高,GMT增长倍数较多,具有良好的免疫原性。     

福氏2a痢疾结合疫苗临床安全性和免疫原性研究

目的 评价福氏2a痢疾结合疫苗临床安全性和免疫原性.方法 按随机、对照、盲法的原则,以不含福氏2a痢疾结合疫苗成份的磷酸缓冲盐水作为安慰剂对照,开展现场临床试验,比较试验疫苗组和对照组免疫后临床反应、抗体阳转率和几何平均滴度(GMT)增长倍数.结果 福氏2a痢疾结合疫苗无严重的全身和局部反应,试验疫苗组和对照组全身和局部反应发生率差异无显著的统计学意义.试验疫苗组经2针全程免疫后2周和12周,抗体阳转(≥4倍增长)率分别为86.27%和79.74%;GMT分别为1:3783.55和1;2983.32;抗体GMT较免疫前分别平均增长12.47倍和9.83倍.而对照组2针免疫后2周和12周,抗体阳转(≥4倍增长)率分别为8.18%和8.49%;GMT分别为1:361.83和1:326.21;抗体GMT较免疫前分别平均增长1.08倍和0.98倍.全程免疫后试验疫苗组与对照组抗体阳转率、GMT、抗体滴度,较免疫前平均增长倍数差异均有非常显著的统计学意义.结论 福氏2a痢疾结合疫苗是安全的,在≥2岁的观察者中有良好的免疫原性.临床试验注册国家食品药品监督管理局<药物临床试验>2003L03808号.     

国产流感裂解疫苗接种人体后安全性和免疫原性评价

目的:评价变更后流感毒株生产的国产流感裂解疫苗安全性和免疫原性。方法:对宁波市宁海县559例分组接种流感裂解疫苗者进行临床指标(局部反应、全身反应)的监测,并抽取其中213例,用流感病毒HI抗体测定法对接种者免疫前后的抗体滴度进行测定,比较免疫前后抗体阳转率及几何平均滴度(GMT)。结果:观察对象接种疫苗后发热反应发生率为1.22%,全身其他反应发生率为1.22%,局部反应发生率为1.07%,且以轻度反应为主。H1N1型、H3N2型、B型免后抗体阳转率分别为84.04%、85.45%、83.57%;不同年龄组免后抗体滴度的增长倍数,H1N1型在5.50～16.00倍之间,H3N2型在13.16～39.33倍之间,B型在7.28～24.85倍之间,各年龄组各抗体型别免疫前后GMT差别均有统计学意义。结论:国产流感裂解疫苗具有良好的安全性和免疫原性。     

麻疹 流行性腮腺炎 风疹活疫苗(M-M-RⅡ)免疫效果观察及免疫程序探讨

选择在8～9月龄时已完成麻疹减毒活疫苗（MV）初免的11～16月龄儿童为观察对象,对麻疹、流行性腮腺炎（腮腺炎）、风疹活疫苗（M－M－RⅡ）的免疫效果进行了观察,并探讨其免疫程序．M－M－RⅡ免疫后麻疹血凝抑制（HI）抗体阳性率100％,抗体≥4倍增长率为55．42％,几何平均滴度（GMT）1：46．60,较免疫前增长2．27倍;腮腺炎HI抗体阳转率95.23％,GMT1：9．60;风疹HI抗体阳转率100％,GMT1：392．47．作者认为,在上海市M－M－RⅡ初始免疫程序确定为已完成MV初免的12～18月龄儿童是合理的,且能产生理想的免疫效果．     

2009年北京市大兴区健康人群甲型H1N1流感抗体水平监测及接种甲型H1N1流感疫苗免疫效果

目的了解人群甲型H1N1流感抗体水平及甲型H1N1流感疫苗的免疫效果,为甲型H1N1流感疫苗的科学使用提供依据。方法选择北京市大兴区庞各庄镇、安定镇、黄村镇、亦庄镇和兴丰街道5个地区各年龄组共200人作为人群抗体监测对象,其中各年龄组共选择50人作为免疫效果评估对象,抽取静脉血250份,采用血凝抑制实验方法测定HI抗体。结果 200人中抗体阳性者48人,阳性率为24%,几何平均滴度(GMT)为1:80.25,不同性别、地区人群的HI抗体阳性率差异无统计学意义。10～20岁和60岁以上组人群抗体阳性率最高,分别为42%和40%。监测免疫后人群50人,免疫成功率为92%,GMT是免疫前的8.7倍。结论大兴区已有24%的人群具有甲型H1N1流感保护性抗体;甲型H1N1流感疫苗具有良好的流行病学保护效果。     

甲型H1N1流感疫苗免疫原性及安全性评价

目的 评价2种国产新型甲型H1N1流感病毒裂解疫苗的免疫原性与安全性.方法 采用随机、双盲、对照方法,选取≥3岁健康志愿者748人,分为2组,分别于0、21 d接种甲、乙2种不同疫苗,剂量均为15μg血凝素/剂,并分别测定比较0、21和42 d的抗体阳转率、疫苗保护率和血清HI抗体滴度,判定其免疫原性;观察比较接种后不良反应率,评价其安全性.结果 甲、乙2种疫苗免疫后21、42 d抗体阳转率分别为81.39%、92.01%和94.05%、95.80%,抗体保护率分别为84.17%、95.36%和96.88%、99.21%,几何平均滴度(GMT)增长倍数分别为34.37、55.34倍和43.69、57.20倍;疫苗接种后30 min内,发热发生率分别为9.44%、14.69%和4.53%、2.36%;除42 d抗体阳转率和发热发生率外,其余各指标在2种疫苗问的差异均有统计学意义.结论 甲、乙2种疫苗均具有良好的免疫原性和安全性.     

麻疹减毒活疫苗初免的血清学效果及其影响因素

本文报告了不同剂量麻疹减毒活疫苗(沪191)对503名不同月龄儿童进行初免及免后一年的血清学结果。503名儿童中,抗体阳转461名,阳转率为91.65%,GMT为1:266.74,达保护滴度者比例为46.52%。0.2ml、0.3ml和0.5ml麻苗的免疫效果无显著性差异。6月龄初免者,不论抗体阳转率、GMT,还是达保护滴度者比例均显著低于7月龄和8月龄以上组。初免后一年时3个月龄组的抗体阳性率、GMT及达保护滴度者比例均有不同程度的下降,尤以6月龄初免组下降最明显,说明麻苗8月龄初免是合适的。研究结果表明,现行麻苗免疫成功率虽高,但抗体滴度较低,建议研制免疫原性更强的新型麻苗。     

甲肝减毒活疫苗(H_2株)二针法免疫效果观察

目的　观察甲肝活疫苗 (H2 株 )二针法的免疫原性。方法　用 0、 6免疫程序 ,选 85名免前抗HAV IgG阴性的易感者接种甲肝活疫苗 (TCID5 0 =10 6 5 /ml)。结果　一针免后 1月血清抗体阳转率 10 0 % ,抗体几何平均滴度 (GMT1 )等于 7 2 8± 2 2 1。二针免后 1月 ,抗体阳转率仍为 10 0 % ,GMT2 等于 48 7± 2 2 3 ,再免后抗体滴度比一针增加了 6 7倍。结论　 89 4%的再免者抗体均有增长 ,其中增长 4倍以上的占 74 1%。     

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。     

北京市顺义区健康人群甲型H1N1流感抗体水平及其疫苗免疫效果

目的了解北京市顺义区健康人群甲型H1N1流感抗体水平,评价甲型H1N1流感疫苗免疫效果,为卫生部门制定预防控制措施和策略提供依据。方法随机选取顺义区12个乡街的5岁以上健康人群(202名)采集免疫前静脉血检测抗体,评估健康人群抗体水平;接种甲型H1N1流感疫苗后,各年龄组随机选取部分人群做免疫后抗体水平检测,评估疫苗免疫效果。结果 202份血清标本中甲型H1N1流感抗体水平阳性率46.53%(94/202),与北京市人群甲型H1N1流感抗体水平检测结果差异有统计学意义。抗体几何平均滴度倒数(GMRT)为32.78。不同性别人群之间甲型H1N1流感抗体阳性率差异无统计学意义,不同年龄组之间抗体水平阳性率差异有统计学意义,25~29岁、10~14岁组抗体水平阳性率高。50名评估对象免疫前抗体阳性率50%(25/50),免疫后抗体阳性率94%(47/50),甲型H1N1流感抗体阳转率80%(30/50)。免疫前阴性和阳性评估对象之间抗体阳转率差异有统计学意义。评估对象总体抗体滴度呈6倍增高,各年龄组免疫前、后抗体GMRT的变化之间差异有统计学意义,25~29岁、60岁以上组滴度升高倍数最低。结论顺义区甲型H1N1流感实际感染数高于北京市甲型H1N1流感平均感染水平。疫苗接种使目标人群达到了形成该样本人群免疫屏障的要求,提示在甲型H1N1流感大流行之际接种疫苗是控制疫情的必要手段。免疫前抗体水平、年龄是甲型H1N1流感抗体阳转率的影响因素。     

广元市甲型H1N1流感抗体水平调查

目的了解广元市人群甲型H1N1流感病毒感染水平,为评估疫情发展趋势提供信息支持。方法采集不同年龄段的城市和农村人口的血清用血凝抑制实验（HI）方法进行抗体检测,用统计学方法对抗体水平进行分析。结果 2010年共采集754份血清标本,其中甲型H1N1抗体阳性140份,阳性率18.6%,GMT1∶11。不同时间点、不同地区调查对象甲型H1N1抗体水平差异有统计学意义（P〈0.05）,不同性别、不同年龄组之间抗体水平差异无统计学意义（P〉0.05）。多因素logistic回归分析显示,甲型H1N1疫苗接种、调查时间和地区差异与HI抗体阳性呈显著性相关。结论广元市人群中18%以上具有甲型H1N1流感保护抗体,但抗体水平仍然较低,应进一步加强甲型H1N1流感疫苗的宣传和接种。     

北京市人群甲型H1N1流感血清流行病学调查

目的 了解和掌握北京市人群对甲型H1N1流感的免疫水平.方法 在2009年11月27日至12月23日从医院患者(排除感染科和呼吸科)、血液中心志愿者和体检中心健康体检者中随机选取调查对象进行问卷调查,并采集血清标本进行甲型H1N1流感病毒血凝抑制(HI)抗体检测.结果 共选取调查对象856名,其中127名(14.8%)调查对象体内甲型H1N1流感病毒HI抗体为阳性.0～5岁、6～17岁、18～55岁、≥56岁年龄组HI抗体阳性率分别为14.5%、19.4%、17.4℅和8.0%(P=0.009).不同性别HI抗体阳性率差异无统计学意义(P=0.693).人群血清HI抗体年龄加权阳性率为15.8%.多因素logistic回归分析显示,年龄、出现过急性呼吸道症状以及接种甲型H1N1流感疫苗与HI抗体阳性呈显著性相关.结论 北京市已经有超过15%的人群具有甲型H1N1流感保护性抗体,普通人群中已经建立一定的免疫屏障.     

四川省成都市甲型H1N1流感血清学调查结果分析

目的了解成都市人群甲型H1N1流感感染现状。方法按照国家方案采集不同年龄组人群血清标本,用血凝抑制(HI)试验方法进行抗体检测,HI抗体滴度≥1∶40判为阳性。结果成都市甲型H1N1流感阳性率8.85%(108/1221);13～17岁组阳性率最高(13.85%,P0.05);男女性阳性率差异无统计学意义;就诊人群阳性率低于一般人群,但差异无统计学意义。结论成都市发生了甲型H1N1流感社区流行,但在人群中的自然感染未形成有效免疫屏障,甲型H1N1流感疫苗接种仍有必要。     

Serologic survey of pandemic influenza A (H1N1 2009) in Beijing, China

Objective

To examine the frequency and distribution of antibodies against pandemic influenza A (H1N1 2009) [H1N1] in populations in Beijing and elucidate influencing factors.

Methods

In January 2010, a randomized serologic survey of pandemic influenza A (H1N1 2009) was carried out. Six districts that were randomly selected with a total of 4601 participants involved in the survey have their antibody level tested by hemagglutination inhibition assay.

Results

Among the 4601 participants, the overall seropositive rate for pandemic influenza A (H1N1 2009) antibodies was 31.7%. The seropositivity prevalence in participants who received the pandemic H1N1 vaccination was 60.9%. Only 53.1% of the pandemic influenza A (H1N1 2009) seropositive individuals who had not received the vaccination experienced respiratory tract infection symptoms. Multivariate logistic regression revealed that factors such as age, occupation, dwelling type, whether the participant's family included students in school, and the vaccination history with pandemic influenza A (H1N1 2009) were associated with antibody titers (p < 0.05).

Conclusions

Our data indicated that almost 30.0% of the residents had appropriate antibody titers against pandemic influenza A (H1N1 2009) in Beijing, and these titers may provide an immune barrier.     

职业暴露人群A(H5N1)和甲型H1N1流感血清抗体分析

目的:了解人禽流感A(H5N1)和甲型H1N1流感职业暴露人群中的感染状况。方法:对职业暴露人群进行个案调查,采用血凝抑制法(HI)检测职业暴露人群血清中人禽流感A(H5N1)和甲型H1N1流感抗体。结果:2009年-2010年采集的624份职业暴露人群血清中未检测出人禽流感A(H5N1)抗体,而在2009年采集的血清中有5份检测出甲型H1N1流感抗体,抗体阳性率为1.55%,2010年采集的血清中抗体阳性率为11.96%,其中<29岁阳性率为17.19%,30岁～59岁阳性率为10.87%。结论:职业暴露人群中未检测出A(H5N1)流感抗体,但仍需加强职业暴露人群监测。同时甲型H1N1流感抗体水平较低,缺乏相应的抗体水平保护。     

An adjuvanted pandemic influenza H1N1 vaccine provides early and long term protection in health care workers

Mass vaccination was the most effective prophylaxis for protecting the population during the influenza H1N1 pandemic. We have evaluated the tolerability, immunogenicity and kinetics of the antibody response to a monovalent oil-in-water (AS03) adjuvanted human pandemic split influenza A/California/7/2009 H1N1 (3.75 μg haemagglutinin) vaccine in health care workers. Vaccination elicited a rapid and early protective level of haemagglutination inhibition antibody from 6 to 7 days post vaccination, and by 14 to 21 days post vaccination, up to 98% of vaccinees had protective antibody titres which persisted for at least 3 months in 84-92% of subjects. A rapid induction of protective antibody is important in reducing community spread of pandemic influenza and in helping maintain the integrity of the health care system during the pandemic.     

Comparison of Pandemic (H1N1) 2009 and Seasonal Influenza, Western Australia, 2009

We compared confirmed pandemic (H1N1) 2009 influenza and seasonal influenza diagnosed in Western Australia during the 2009 influenza season. From 3,178 eligible reports, 984 pandemic and 356 seasonal influenza patients were selected; 871 (88.5%) and 288 (80.9%) were interviewed, respectively. Patients in both groups reported a median of 6 of 11 symptoms; the difference between groups in the proportion reporting any given symptom was <10%. Fewer than half the patients in both groups had >1 underlying condition, and only diabetes was associated with pandemic (H1N1) 2009 influenza (odds ratio [OR] 1.9, 95% confidence interval [CI] 1.1–3.5). A total of 129 (14.8%) persons with pandemic (H1N1) 2009 and 36 (12.5%) persons with seasonal influenza were hospitalized (p = 0.22). After controlling for age, we found that patient hospitalization was associated with pandemic (H1N1) 2009 influenza (OR 1.5; 95% CI 1.1–2.1). Contemporaneous pandemic and seasonal influenza infections were substantially similar in terms of patients’ symptoms, risk factors, and proportion hospitalized.     

Risk factors for pandemic (H1N1) 2009 seroconversion among adults, Singapore, 2009

A total of 828 community-dwelling adults were studied during the course of the pandemic (H1N1) 2009 outbreak in Singapore during June-September 2009. Baseline blood samples were obtained before the outbreak, and 2 additional samples were obtained during follow-up. Seroconversion was defined as a >4-fold increase in antibody titers to pandemic (H1N1) 2009, determined by using hemagglutination inhibition. Men were more likely than women to seroconvert (mean adjusted hazards ratio [HR] 2.23, mean 95% confidence interval [CI] 1.26-3.93); Malays were more likely than Chinese to seroconvert (HR 2.67, 95% CI 1.04-6.91). Travel outside Singapore during the study period was associated with seroconversion (HR 1.76, 95% CI 1.11-2.78) as was use of public transport (HR 1.81, 95% CI 1.05-3.09). High baseline antibody titers were associated with reduced seroconversion. This study suggests possible areas for intervention to reduce transmission during future influenza outbreaks.     

Response to 2009 pandemic and seasonal influenza vaccines co-administered to HIV-infected and HIV-uninfected former drug users living in a rehabilitation community in Italy

Background

2009 A(H1N1) pandemic influenza vaccination was recommended as a priority to essential workers and high-risk individuals, including HIV-infected patients and people living in communities.

Methods

HIV-infected and HIV-uninfected former drug-users (18-60 years old) living in a rehabilitation community (San Patrignano, Italy) received one dose of a MF59-adjuvanted 2009 pandemic influenza vaccine and one dose of a 2009-2010 seasonal trivalent inactivated influenza vaccine (containing A/Brisbane/59/2007(H1N1), A/Brisbane/10/2007(H3N2), B/Brisbane/60/2008) simultaneously. Antibodies against each vaccine antigen were determined at the time of vaccination and one and six months post-vaccination by hemagglutination-inhibition test.

Results

49 HIV-infected and 60 HIV-uninfected subjects completed the study. Most (98%) HIV-infected participants were on antiretroviral treatment, the median CD4+ cell count was 350 (IQR 300) cells/μl and viremia was suppressed in 91.8% of cases. One month post-vaccination, no significant changes in immune-virological parameters were observed. One month post-vaccination, the immune responses to both pandemic and seasonal vaccine met the EMA-CPMP criteria for immunogenicity of influenza vaccines in both HIV-infected and HIV-uninfected subjects. No difference in vaccine responses was observed between the two groups. Six months after vaccination, the percentages of vaccinees with antibody titres ≥1:40 and antibody geometric mean titres significantly decreased in both groups. However, they were significantly lower in HIV-infected than in HIV-uninfected vaccinees. In subjects who had been primed to seasonal influenza the year before (through either vaccination or natural infection), levels of antibodies against 2009 A(H1N1) were higher than those measured in unprimed subjects, both one month and six months post-vaccination.

Conclusions

The co-administration of a single dose of 2009 pandemic MF59-adjuvanted influenza vaccine with a seasonal vaccine provided a protective immune response in both HIV-infected and HIV-uninfected individuals. Subjects who had been primed to seasonal influenza in the year preceding the pandemic had a more vigorous and long-lasting antibody response to 2009 pandemic vaccine.