脊髓灰质炎疫苗2种序贯免疫程序不同免疫剂次免疫效果的评估

目的评估脊髓灰质炎疫苗2种序贯程序下不同剂次的免疫效果,为新免疫策略和免疫程序制定提供依据。方法 2016—2017年随机抽取天津市适龄接种脊髓灰质炎疫苗的新生儿128人,分A、B、C 3组,A组42人,B组44人,C组42人。A、B 2组接种1剂脊髓灰质炎灭活疫苗(IPV)和2剂脊髓灰质炎减毒活疫苗(OPV)(I-O-O),C组接种3剂IPV(I-I-I)。各组研究对象分别于接种疫苗后不同时间点采血,采用微量中和试验进行抗体检测,并对抗体阳性率和抗体几何平均滴度水平(GMT)进行分析。结果接种1剂次IPV后,A组Ⅰ型、Ⅱ型、Ⅲ型脊髓灰质炎抗体阳转率分别为69.05%(29人)、71.43%(30人)、71.43%(30人)(P0.05),抗体阳性率分别为97.62%(41人)、95.24%(40人)、80.95%(34人),3型脊髓灰质炎抗体GMT间差异无统计学意义(P0.05);接种OPV2或IPV2后,除B组Ⅲ型阳性率为97.73%(43人)外,B组Ⅰ型、Ⅱ型及C组各型阳性率均达到100%,仅Ⅱ型脊髓灰质炎抗体GMT在B、C组间(B组357.42,C组172.28)差异有统计学意义(P0.05);按I-O-O完成全程接种后,A组各型脊髓灰质炎抗体阳性率均为100%,3型脊髓灰质炎抗体GMT分别为1 075.05、464.67、786.53(P0.05)。结论接种1剂次IPV或接种IPV1+OPV2后各型脊髓灰质炎抗体阳性率未全部达到100%,接种2剂次IPV后各型脊髓灰质炎抗体阳性率均可达到100%;I-O-O序贯程序可以诱导研究对象产生保护性抗体,但在降低脊髓灰质炎的发生可能性方面,I-I-O序贯程序优于I-O-O。     

不同序贯程序的脊髓灰质炎灭活疫苗和减毒活疫苗的免疫效果研究

目的 评价脊髓灰质炎灭活疫苗（IPV）和减毒活疫苗（OPV）不同序贯免疫程序的免疫效果。方法 选取月龄≥2月的婴儿,分为1剂IPV和2剂OPV序贯组(I - O - O组)、2剂IPV和1剂OPV序贯组(I - I - O组)、IPV全程(I - I - I组)和OPV全程组(O - O - O),分别在2、3、4月龄时各接种1针,检测并比较各组人群血清中脊髓灰质炎中和抗体几何平均滴度（GMT）及抗体阳转率。结果 在完成基础免疫后,I - O - O 组Ⅰ、Ⅱ、Ⅲ型抗体GMT分别为948.78、930.91、955.08;I - I - O组抗体GMT分别为909.43、1 202.34、1 102.83;I - I - I 组GMT分别为333.02、298.56、411.98,O - O - O组抗体GMT分别为814.42、778.27、658.52;差异均有统计学意义;各组3个型别的抗体阳转率均为98％~100％,差异无统计学意义。接种1针IPV后脊髓灰质炎Ⅰ型、Ⅱ型、Ⅲ型中和抗体GMT分别为21.77、30.89、26.46,抗体阳转率分别为84.1％、91.5％、91.5％;接种第2剂IPV后,Ⅰ型、Ⅱ型、Ⅲ型中和抗体GMT分别69.42、133.89、212.58,抗体阳转率分别为100.0％、100.0％、99.9％。结论 IPV与OPV序贯接种后,对象产生的脊髓灰质炎中和抗体GMT比单独接种3剂IPV或3剂OPV高;不同序贯程序中,接种2剂IPV后抗体保护率较高。为了使机体产生更高的抗体水平并且避免疫苗相关麻痹病例发生,可采用IPV与OPV序贯程序,并以2剂IPV和1剂OPV的序贯程序为佳。     

首剂IPV纳入免疫规划前儿童脊髓灰质炎疫苗接种情况分析

目的了解首剂脊髓灰质炎灭活疫苗(IPV)纳入免疫规划(EPI)前宁波市鄞州区儿童脊髓灰质炎疫苗(PV)接种情况。方法通过宁波市免疫规划信息管理系统收集2011—2014年出生,且全程完成PV基础免疫的儿童接种资料,对首针PV(PV1)和基础免疫程序构成情况做描述性统计分析。结果鄞州区儿童基础免疫全程接种率为99.91%。儿童PV1以脊灰减毒活疫苗(OPV)为主,占72.11%,IPV与吸附无细胞百白破、灭活脊髓灰质炎和b型流感嗜血杆菌(结合)联合疫苗(DTa P-IPV/Hib)分别占16.30%和11.59%。基础免疫程序以OPV全程(O-O-O型)为主,占71.85%,替代程序以IPV全程(I-I-I型)和DTa P-IPV/Hib全程(D-D-D型)为主,分别占15.05%和11.50%。不同户籍、地区、出生年份及经济水平儿童的PV1采用疫苗和基础免疫程序构成均有所不同(P0.01)。出生年份越晚的儿童,PV1采用OPV的比例越低,采用IPV和DTa PIPV/Hib的比例相对越高;基础免疫采用O-O-O型的比例越低,采用I-I-I型和D-D-D型的比例相对越高(均P0.01)。结论鄞州区儿童PV基础免疫全程接种率高,PV1和基础免疫全程接种灭活类脊灰疫苗比例呈逐年增高趋势,在首剂IPV纳入EPI前已具备一定工作基础,但应注意人群和地区差异。     

宁波市鄞州区2008～2014年出生儿童脊髓灰质炎灭活疫苗基础免疫全程替代接种情况分析

目的了解宁波市鄞州区2008~2014年出生儿童脊髓灰质炎(脊灰)灭活疫苗(IPV)替代口服脊灰减毒活疫苗(OPV)基础免疫情况,为调整脊灰疫苗(PV)免疫策略提供参考。方法通过宁波市免疫规划信息管理系统收集2008~2014年出生儿童的PV基础免疫资料,对IPV替代接种现状进行描述性分析,采用Logistic回归模型进行多因素分析。结果宁波市鄞州区2008~2014年出生儿童125 555人,PV基础免疫全程接种率为99.92%,IPV全程替代率为16.42%;IPV全程替代率随儿童年龄增长呈下降趋势(x2=21 039.53,P<0.001);多因素分析表明,本地户籍儿童全程替代率高于外地户籍儿童(OR=3.22,95%CI=3.11~3.34);城区全程替代率高于农村地区(OR=1.31,95%CI=1.26~1.36);与Ⅲ类经济水平地区相比,Ⅱ类(OR=1.41,95%CI=1.32~1.51)和Ⅰ类(OR=1.09,95%CI=1.03~1.17)全程替代率更高;替代免疫程序以I-I-I型(3剂次均为IPV)和D-D-D型(3剂次均为DTa PIPV/Hib)为主,分别占53.35%和40.56%,二者全程替代接种的比例均呈逐年递增趋势(x2=215.84,P<0.001;x2=588.01,P<0.001);序贯免疫以I-I-O型(IPV-IPV-OPV)和I-O-O型(IPV-OPV-OPV)为主,分别占3.07%和1.58%,其他替代程序占1.44%。结论宁波市鄞州区儿童IPV基础免疫全程替代率低,存在人群和地区差异性;替代免疫程序种类较多,需通过健康教育提高家长科学选择替代免疫程序。     

梅州市Sabin株脊髓灰质炎灭活疫苗替代减毒活疫苗序贯程序免疫效果

目的在消灭脊髓灰质炎(脊灰)后期,分析用Sabin株脊灰灭活疫苗(IPV)替代首剂脊灰减毒活疫苗(OPV)的"1剂Sabin株IPV+3剂OPV序贯程序"的有效性、安全性。方法采用描述流行病学方法,对梅州市2008—2017年急性弛缓性麻痹(AFP)病例、2015年12月—2017年11月Sabin株IPV替代首剂OPV免疫后疑似预防接种异常反应(AEFI)病例监测结果进行分析。结果免疫策略调整前8年梅州市发生4例疫苗相关麻痹型脊灰(VAPP),发病率为0.21/10万。Sabin株IPV替代首剂OPV后,可获得较好的脊灰中和抗体保护率,2年未发生VAPP、疫苗衍生脊灰病毒(VDPV)病例。主动、被动监测结果显示,AEFI发生率分别为542.51/10万、65.52/10万,以一般反应为主,异常反应发生率和同期接种的第一、二类疫苗性差异无统计学意义。结论梅州市采用"1剂次Sabin株IPV+3剂次OPV"的序贯免疫程序2年来,保持高水平脊灰免疫屏障,消除脊灰野毒株传入的风险,并且防止了VAPP、VDPV病例的发生。     

脊髓灰质炎疫苗序贯免疫程序的研究与应用进展

脊髓灰质炎(脊灰)是由脊灰病毒引起的急性肠道传染病,传播广泛,对儿童的健康和生命危害极大。口服脊灰减毒活疫苗(Oral Attenuated Poliovirus Vaccine,OPV)是全球消灭脊灰行动的首选疫苗,已使II型脊灰野病毒于1999年在全球消灭;但在极少情况下会发生疫苗相关麻痹型脊灰(Vaccine-associated Paralytic Poliomyelitis,VAPP)和疫苗衍生脊灰病毒(Vaccine-derived Poliovirus,VDPVs)病例。为了避免这些风险,许多国家常规免疫规划已不再单独使用OPV,而是改用脊灰灭活疫苗(Inactivated Polio Vaccine,IPV)。这些国家在OPV转换成IPV期间,大部分采用了先接种1~2剂IPV,再接种≥2剂OPV的序贯免疫程序。IPV-OPV序贯免疫方案可减少或预防VAPP,同时又能保持较高的体液免疫和肠道黏膜免疫力,能更好地阻断脊灰野病毒在自然界的循环。根据WHO建议,常规免疫规划中只使用OPV的国家应当调整脊灰免疫策略,引进至少1剂次IPV,采取IPV-OPV序贯免疫策略或联合使用OPV和IPV的策略。相信这些转变将会加快全球消灭脊灰野毒株的进程,对实现全球最终根除脊灰的目标具有重要的意义。     

中国脊髓灰质炎疫苗免疫策略的思考及建议

脊髓灰质炎(脊灰)曾在中国广泛流行,接种脊灰疫苗是消灭脊灰最有效的手段。脊灰有两种疫苗—口服脊灰减毒活疫苗(Oral poliomyelitis attenuated live vaccine,OPV)和脊灰灭活疫苗(Inactivated poliomyelitis vaccine,IPV)。两种疫苗的接种均可实现消灭脊灰野病毒(Wild poliovirus,WPV)的目标。目前全球WPV病例数已经达到历史最低水平,Ⅱ型疫苗衍生脊灰病毒(Type 2 vaccine-derived poliovirus,VDPV2)病例数远超过WPV病例数。为了最终实现消灭所有脊灰病例的目标,世界卫生组织提出全球最终将停止接种OPV,使用IPV的建议。本文根据全球消灭脊灰形势的变化,结合中国维持无脊灰工作进展和需要,提出中国脊灰疫苗免疫策略,即在保证国产IPV供应基础上,由目前的1剂IPV加3剂二价OPV(Bivalent oral polio vaccine,bOPV)的常规免疫程序,过渡到2剂IPV加2剂bOPV的免疫程序,直至全球消灭脊灰证实后,在常规免疫接种中停用bOPV,全程接种IPV。     

脊髓灰质炎灭活疫苗基础免疫效果观察

目的 考察灭活脊髓灰质炎疫苗(inactivated poliomyelitis vaccine,IPV)在中国婴儿中的免疫效果,并与目前常规使用的口服脊髓灰质炎减毒活疫苗(oral poliomyelitis vaccine,OPV)进行比较.方法 对2个月龄婴儿采用组群随机法分为2个组,每组208名,分别接种IPV和OPV,并采集免疫前后血清.采用微量中和方法,对血清中抗脊髓灰质炎病毒3个型的中和抗体进行测定,对于抗体保护率比较采用X2检验进行统计学处理.抗体滴度进行对数转换后采用Z检验进行比较,所有统计学检验以P<0.05来确定差异是否具有统计学意义.结果婴儿经初次免疫后,IPV组Ⅰ、Ⅱ、Ⅲ型病毒中和抗体保护率分别为100.0%(186/186)、97.3%(181/186)、98.9%(184/186),几何平均滴度(GMT)分别为151.2、86.7、211.3,OPV组Ⅰ、Ⅱ、Ⅲ型病毒中和抗体保护率分别为97.4%(188/193)、100.0%(193/193)、95.3%(184/193),GMT分别为1089.5、538.2、203.7.两组中Ⅰ、Ⅱ型的保护率差异没有统计学意义(Ⅰ、Ⅱ型分别为X2Ⅰ=2.991,P=0.084;X2Ⅱ=3.512,P=0.061),但Ⅲ型中差异有统计学意义(X2Ⅱ=4.143,P=0.042).IPV组Ⅰ、Ⅱ型抗体几何平均滴度低于OPV疫苗,差异有统计学意义(ZⅠ=12.537,P=0.000;ZⅡ=13.415,P=0.000),而Ⅲ型抗体几何平均滴度差异没有统计学意义(ZⅢ=0.067,P=0.947).结论 经基础免疫后IPV在婴儿中免疫效果良好,和OPV相比,IPV组Ⅰ、Ⅱ型保护率与OPV相当,Ⅲ型高于OPV组.IPV组Ⅰ、Ⅱ型抗体几何平均滴度低于OPV疫苗,而Ⅲ型抗体几何平均滴度与OPV组相当.     

国产Sabin株脊髓灰质炎灭活疫苗接种后的安全性调查

目的评价国产Sabin株脊髓灰质炎(脊灰)灭活疫苗(Inactivated poliomyelitis vaccine,IPV)接种后的安全性,为中国脊灰疫苗免疫策略的调整提供依据。方法采用主动监测方法于2015年9月-2016年2月收集宁夏回族自治区同心县所有适龄儿童接种国产Sabin株IPV和三价脊灰减毒活疫苗(t OPV)后的不良反应,采取被动监测方法通过中国免疫规划信息管理系统收集2008-2016年宁夏全区国产Sabin株IPV、t OPV及其他免疫规划(EPI)疫苗的不良反应数据,比较分析不良反应发生率。结果主动监测显示接种国产IPV、t OPV后的一般反应发生率分别为2 464.33/10万剂、64.92/10万剂。被动监测显示,接种国产IPV的一般反应、异常反应发生率分别为51.68/10万剂、1.67/10万剂;接种t OPV后的一般反应、异常反应发生率分别为1.73/10万剂、0.22/10万剂。与其他EPI疫苗相比,国产IPV一般反应发生率最高,但其异常反应发生率低于麻疹减毒活疫苗、白喉破伤风联合疫苗、麻腮风联合减毒活疫苗、麻疹风疹联合减毒活疫苗和卡介苗,且无严重异常反应发生。结论接种国产Sabin株IPV安全性良好;主动监测的灵敏性高于被动监测。     

脊髓灰质炎疫苗3种免疫程序不良反应评价

目的 评价脊髓灰质炎(脊灰)疫苗3种免疫程序的不良反应。方法 于2018年11—12月,选择河北省邯郸市肥乡区的8个预防接种门诊接种脊髓灰质炎灭活疫苗(inactivated poliovirus vaccine,IPV)和Ⅰ型Ⅲ型二价脊髓灰质炎减毒活疫苗(bivalent oral poliovirus vaccine,bOPV)的≥2月龄健康婴儿,随机分为IPV-bOPV-bOPV(a组)、IPV-IPV-bOPV(b组)及IPV-IPV-IPV (c组)3个免疫程序组,每组均为72人,按照免疫程序分别在2、3、4月龄接种IPV或/和bOPV;采取主动监测方式收集3组受种儿每次接种后的疑似预防接种异常反应(adverse events following immunization,AEFI)发生情况,比较3种免疫程序的AEFI报告发生率,并根据《全国疑似预防接种异常反应监测方案》进行分类,评价3种免疫程序的不良反应。结果 共报告AEFI 16例,AEFI报告发生率为2.52/100剂,a组、b组和c组分别报告AEFI 5例(2.23/100剂)、2例(0.97/100剂)、9例(4...     

Immune response to simultaneous administration of a combined measles,mumps and rubella vaccine with booster doses of diphtheria-tetanus and poliovirus vaccine

A combined vaccine against measles (Edmonston-Zagreb 19 strain), mumps (Rubini strain) and rubella (Wistar RA 27/3 strain) was administered to a group of 46 children aged 10–12 months simultaneously with booster doses of compulsory diphtheria-tetanus toxoid and oral poliovirus vaccine. A second group of 53 children aged 15–24 months who had received booster doses of the compulsory vaccines 5 to 12 months before was also vaccinated.The same seroconversion rates (100%) and similar antibody titers for rubella were observed in both groups. The same seroconversion rates for mumps (93%) and similar rates for measles (98 and 94%) were observed in the two groups.Significantly lower antibody titers for measles and mumps were found in the first group, but they were compensated by an earlier protection, a reduction of number of visits for immunization, costs for the community, and improvement in parental compliance.These results confirm that Edmonston-Zagreb 19 and Rubini strains are still immunogenic even when they are combined with Wistar RA 27/3 strain. Moreover, a long term follow-up in order to verify the persistence of protective antibody levels in both groups of children, could suggest that combined measles, mumps and rubella vaccine could be given earlier (at 10–12 months of age), simultaneously with booster doses of diphtheria and tetanus toxoid and of trivalent oral poliovirus vaccine.     

Evaluation of vaccine derived poliovirus type 2 outbreak response options: A randomized controlled trial,Karachi, Pakistan

BackgroundOutbreaks of circulating vaccine derived polioviruses type 2 (cVDPV2) remain a risk to poliovirus eradication in an era without live poliovirus vaccine containing type 2 in routine immunization. We evaluated existing outbreak response strategies recommended by the World Health Organization (WHO) for control of cVDPV2 outbreaks.MethodsSeronegative children for poliovirus type 2 (PV2) at 22 weeks of life were assigned to one of four study groups and received respectively (1) one dose of trivalent oral poliovirus vaccine (tOPV); (2) monovalent OPV 2 (mOPV2); (3) tOPV together with a dose of inactivated poliovirus vaccine (IPV); or (4) mOPV2 with monovalent high-potency IPV type 2. Stool and blood samples were collected and assessed for presence of PV2 (stool) and anti-polio antibodies (sera).ResultsWe analyzed data from 265 children seronegative for PV2. Seroconversion to PV2 was achieved in 48, 76, 98 and 100% in Groups 1–4 respectively. mOPV2 was more immunogenic than tOPV alone (p < 0.001); and OPV in combination with IPV was more immunogenic than OPV alone (p < 0.001). There were 33%, 67%, 20% and 43% PV2 excretors in Groups 1–4 respectively. mOPV2 resulted in more prevalent shedding of PV2 than when tOPV was used (p < 0.001); and tOPV together with IPV resulted in lower excretion of PV2 than tOPV alone (p = 0.046).ConclusionmOPV2 was a more potent vaccine than tOPV. Adding IPV to OPV improved immunological response; adding IPV also seemed to have shortened the duration of PV2 shedding. mIPV2 did not provide measurable improvement of immune response when compared to conventional IPV. WHO recommendation to use mOPV2 as a vaccine of first choice in cVDPV2 outbreak response was supported by our findings.Clinical Trial registry number: NCT02189811.     

Inactivated poliovirus vaccine and the final stages of poliovirus eradication

The use of the inactivated poliovirus vaccine (IPV) will increase before and probably also after the global eradication of the wild type poliovirus. Before eradication, the switch from the use of oral poliovirus vaccine (OPV) to IPV has been due to the better safety record of IPV. Introduction of IPV in the regular immunisation schedules is made easier by the development of several combination vaccines, including IPV. Maternal antibodies and young age, often considered problematic for early initiation of IPV schedules, did not compromise optimal maintenance of seropositivity during infancy or long-term persisting antibody levels in our studies. OPV-derived, potentially pathogenic and transmissible poliovirus strains, excreted by some individuals for years, may present a problem for a blunt stopping of all polio immunisations after eradication. Our recent results suggest that locally excreted IgA might have a role in the elimination of poliovirus infection in the intestinal tissues.     

Cost-effectiveness analysis of changing from live oral poliovirus vaccine to inactivated poliovirus vaccine in Australia

OBJECTIVE: Estimate the economic impact of introducing inactivated poliovirus vaccine (IPV) into the Australian childhood immunisation schedule to eliminate vaccine-associated paralytic poliomyelitis (VAPP). METHODS: Cost-effectiveness of two different four-dose IPV schedules (monovalent vaccine and IPV-containing combination vaccine) compared with the current four-dose oral poliovirus vaccine (OPV) schedule for Australian children through age six years. Model used estimates of VAPP incidence, costs, and vaccine utilisation and price obtained from published and unpublished sources. Main outcome measures were total costs, outcomes prevented, and incremental cost-effectiveness, expressed as net cost per case of VAPP prevented. RESULTS: Changing to an IPV-based schedule would prevent 0.395 VAPP cases annually. At $20 per dose for monovalent vaccine and $14 per dose for the IPV component in a combination vaccine, the change would incur incremental, annual costs of $19.5 million ($49.3 million per VAPP case prevented) and $6.7 million ($17.0 million per VAPP case prevented), respectively. Threshold analysis identified break-even prices per dose of $1 for monovalent and $7 for combination vaccines. CONCLUSIONS: Introducing IPV into the Australian childhood immunisation schedule is not likely to be cost-effective unless it comes in a combined vaccine with the IPV-component price below $10. IMPLICATIONS: More precise estimates of VAPP incidence in Australia and IPV price are needed. However, poor cost-effectiveness will make the decision about switching from OPV to IPV in the childhood schedule difficult.     

预防疫苗衍生脊髓灰质炎病毒的传播

自1988年世界卫生组织（WHO）提出在全球范围内消灭脊髓灰质炎（脊灰）的目标后,世界各国大力开展口服脊灰减毒活疫苗（OPV）的计划免疫,脊灰发病率明显下降。目前美洲、欧洲和西太平洋地区已消灭了本土脊灰野病毒的传播。本病的流行国家已由1988年的125个降至2004年的6个。     

Immunogenicity and tolerability of a virosome influenza vaccine compared to split influenza vaccine in patients with sickle cell anemia

The immunogenicity and tolerability of virosome and of split influenza vaccines in patients with sickle cell anemia (SS) were evaluated. Ninety SS patients from 8 to 34 years old were randomly assigned to receive either virosome (n = 43) or split vaccine (n = 47). Two blood samples were collected, one before and one 4–6 weeks after vaccination. Antibodies against viral strains (2006) A/New Caledonia (H1N1), A/California (H3N2), B/Malaysia were determined using the hemagglutinin inhibition test. Post-vaccine reactions were recorded over 7 days. Seroconversion rates for H1N1, H3N2 and B were 65.1%, 60.4% and 83.7% for virosome vaccine, and 68.0%, 61.7% and 68.0% for split vaccine. Seroprotection rates for H1N1, H3N2 e B were 100%, 97.6% and 69.7% for virosome, and 97.8%, 97.8% and 76.6% for split vaccine. No severe adverse reactions were recorded. Virosome and split vaccines in patients with sickle cell anemia were equally immunogenic, with high seroconversion and seroprotection rates. Both vaccines were well tolerated.