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1.
《Vaccine》2022,40(33):4709-4715
BackgroundTo evaluate the immunogenicity and safety of simultaneous administration of the enterovirus 71 (EV71) vaccine with the measles and rubella (MR) combined vaccine.MethodsIn this phase 4, randomized, open-label and noninferiority study, a total of 680 infants aged 8 months were enrolled and assigned to the simultaneous administration group (infants received the first dose of EV71 vaccine and MR vaccine on Day 0, and the second dose of EV71 vaccine on Day 28), or the separate administration groups (EV71 group: infants received two doses of EV71 vaccine on Day 0 and Day 28, respectively; MR group: infants received MR vaccine on Day 0). Blood sample was obtained on Day 0 and Day 56 to measure antibody responses to each of the antigens in terms of antibody titer or concentration, respectively. Local and systemic adverse reactions (ARs) and other adverse events (AEs) following each dose were monitored and compared among groups.ResultsAfter vaccination, simultaneous administration group showed similar seroconversion rates of antibody against EV71(97.9%), measles (97.4%), and rubella (94.3%) compared to EV71 group (99.6% for anti-EV71) or MR group (98.4% for anti-measles and 98.9% for anti-rubella, respectively). Noninferiority was demonstrated for all antibodies as the lower limits of two-sided 97.5% confidence intervals (CIs) of the difference in seroconversion rates between simultaneous administration group and separate administration groups were above the predefined margin of ?10%. Additionally, the adverse reaction rates were comparable among groups (54.4% in the simultaneous group versus 43.9% in the MR group versus 52.6% in the EV71 group).ConclusionAntibody responses induced by simultaneous administration of EV71 vaccine with MR vaccine were robust and noninferior to those by single administration alone. Like the previous findings by single administration alone, simultaneous administration demonstrated comparable reactogenicity and safety profiles. 相似文献
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目的了解2017-2021年中国肠道病毒71型(EV71)灭活疫苗接种现状, 为制定手足口病防控和免疫策略提供参考。方法利用中国免疫规划信息管理系统收集的EV71灭活疫苗报告接种剂次数和出生人口数据估算2012年以来各出生队列截至2021年底的全国、分省和分地市EV71灭活疫苗累计接种率, 并分析与接种率水平相关的潜在影响因素。结果截至2021年, 全国2012年以来出生队列EV71灭活疫苗估算累计接种率为24.96%, 各省份估算接种率为3.09%~56.59%, 各地市估算接种率为0~88.17%。不同地区疫苗接种率与该地区既往手足口病报告发病水平和人均可支配收入的相关性均有统计学意义。结论 2017年以来EV71灭活疫苗在全国范围内应用广泛, 但地区间疫苗接种覆盖情况差异较大, 经济相对发达地区接种率较高, 既往疾病流行强度可能对疫苗的接受度和接种服务模式产生一定影响。EV71灭活疫苗接种对手足口病流行的影响还需进一步研究。 相似文献
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《Vaccine》2020,38(7):1804-1809
BackgroundHand, foot, and mouth disease (HFMD) caused by enterovirus A71 (EV-A71) is a major public health issue in China that poses severe risks to children’s health, especially those under the age of 3. Since 2016, EV71 vaccines developed by three Chinese manufacturers have been approved for use, and clinical trials of these vaccines have demonstrated protection against EV-A71 infection. However, few studies have assessed the effectiveness of these vaccines in real-world settings.MethodsA test-negative design case-control study was used to estimate vaccine effectiveness (VE) in cases of severe HFMD. We obtained information including EV-A71 vaccination status from the Local Center for Disease Control and Prevention (CDC) on all severe HFMD cases under 12 years in age in Guangxi, China, from Jan. 1, 2017, to Dec. 31, 2018. Enterovirus infection was laboratory confirmed by local CDCs. Individuals with a positive EV-A71 nucleic acid test result were assigned to the case group, and those with negative EV-A71 nucleic acid test results were assigned to the control group. We estimated VE using logistic regression.ResultsA total of 2779 severe HFMD cases were enrolled in the study; 838 children were EV-A71 positive cases, and 1941 children were EV-A71 negative controls. The proportion of EV-A71 positive cases aged 6–36 months was lower than that for EV-A71 negative controls. EV-A71 infection was associated with an increased risk of mortality (aOR, 8.8; 95% CI, 1.3–61.6). The adjusted VE was 81.4% and 88.3% for one dose and two doses, respectively.ConclusionOur findings suggest that the rate of EV-A71 has fallen among severe HFMD cases in Guangxi and that the risk for EV-A71 infection in 6–36-month-old children has been reduced by use of the vaccine. Inactivated vaccines performed well in severe HFMD cases in a real-world setting. 相似文献
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《Vaccine》2021,39(31):4296-4305
Enterovirus 71 (EV71) is one of the major causative agents for hand, foot and mouth disease (HFMD) in children. Currently, three inactivated EV71 vaccines have been approved by Chinese government. We previously demonstrated that recombinant EV71 virus-like particles (VLP) produced in Pichia pastoris can be produced at a high yield with a simple manufacturing process, and the candidate vaccine elicited protective humoral immune responses in mice. In present study, the nonclinical immunogenicity, efficacy and toxicity of the EV71 vaccine was comprehensively evaluated in rodents and non-human primates. The immunogenicity assessment showed that EV71 VLPs vaccine elicited high and persistent neutralizing antibody responses, which could be comparable with a licensed inactivated vaccine in animals. The immune sera of vaccinated mice also exhibited cross-neutralization activities to the heterologous subtypes of EV71. Both passive and maternal antigen specific antibodies protected the neonatal mice against the lethal EV71 challenge. Furthermore, nonclinical safety assessment of EV71 VLP vaccine showed no signs of systemic toxicity in animals. Therefore, the excellent immunogenicity, efficacy and toxicology data supported further evaluation of the VLP-based EV71 vaccine in humans. 相似文献
6.
Establishing China's national standards of antigen content and neutralizing antibody responses for evaluation of enterovirus 71 (EV71) vaccines 总被引:2,自引:0,他引:2
Liang Z Mao Q Gao Q Li X Dong C Yu X Yao X Li F Yin W Li Q Shen X Wang J 《Vaccine》2011,29(52):9668-9674
Enterovirus 71 (EV71) is a highly infectious agent that causes hand-foot-mouth disease (HFMD) in humans. Effective vaccination against EV71 infection is critically important, given the recent outbreak of HFMD in the Asia-Pacific region, where it has shown significant mortality and morbidity. There is currently no approved anti-viral therapy available to treat the disease. While several vaccine manufacturers are actively developing EV71 vaccines, there are no international reference standards available to conduct quality control on EV71 vaccines or to assess the effectiveness of EV71 vaccines in immunized populations. In the current report, antigen reference standard based on the C4 subtype of the EV71 vaccine strain was developed. In addition, neutralizing antibody (NTAb) reference panels were analyzed and standards with various neutralizing titers were selected. These reference antigens were used to calibrate vaccine samples from several producers and found that five EV71 antigens and the national reference standards showed good linearity and parallelism. Moreover, mice immunized with various vaccines at doses standardized by these national references showed comparable NTAb responses. Finally, the national NTAb reference panels were found to effectively reduce assay discrepancy between different labs. Taken together, these national reference standards are highly valuable for the standardization and evaluation of EV71 vaccines. 相似文献
7.
Li YP Liang ZL Gao Q Huang LR Mao QY Wen SQ Liu Y Yin WD Li RC Wang JZ 《Vaccine》2012,30(22):3295-3303
There is an urgent need for a novel vaccine that is effective against human Enterovirus 71 (EV71) outbreaks. A double-blind, randomized controlled study was to evaluate the safety and immunogenicity of a human EV71 vaccine in healthy adults, children and infants. The vaccine dosages were 200 U and 400 U for children and adults, and 100 U, 200 U and 400 U for infants. Subjects were randomized to receive different dosages of the vaccine or placebo. Adults received intramuscular injection on Days 0, 14 and 28. Children and Infants received on Days 0, 28 and 56. The novel human EV71 inactivated vaccine was well tolerated and highly immunogenic in healthy volunteers, especially in infant populations. For immune response, the seropositive rates (with titers ≥≥1:8) of neutralizing antibody [NTAb] increased to 100% for all dosage groups after the second vaccination. For NTAb seronegative infants before vaccination, after one dose, the NTAb GMTs were 29.7 (95% CI, 13.1-67.2), 10.1 (95% CI, 6.6-15.3), and 27.4 (95% CI, 14.3-52.2) in the 100 U, 200 U, and 400 U vaccine groups, respectively; after two doses, the GMTs were 114.1 (95% CI, 44.5-292.4), 159.5 (95% CI, 49.3-515.3), and 509.0 (95% CI, 181.3-1429.1), respectively. TRIAL REGISTRATION: ClinicalTrial.gov identifier: NCT01273246 and NCT01273233. 相似文献
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《Vaccine》2018,36(26):3772-3778
Hand, foot and mouth disease (HFMD) primarily affects children younger than 5 years of age. Recently, HFMD has ranked as the top notifiable infectious disease in China. In December 2015, China approved two novel inactivated enterovirus 71 vaccines (EV71 vaccines) for HFMD. Parents’ acceptance is often essential for vaccination program success. The goal of this study was to identify willingness and influential factors to vaccinate among parents of kindergarteners in Guangzhou, China. A cross-sectional survey of face-to-face interviews was conducted from March to July 2016. Fifty-five kindergartens were randomly selected from 11 districts of Guangzhou. An anonymous self-designed questionnaire was used to investigate awareness, knowledge and attitude towards HFMD and EV71 vaccines. A total of 868 parents participated in the survey. Mean(±standard deviation) knowledge score of HFMD was 6.32(±1.70). Approximately 32.03% of parents had heard of the EV71 vaccines with 22.58% receiving information before this study. Nearly 44.24% of parents showed willingness to vaccinate their children. Previously receiving EV71 vaccine-related information [adjusted odds ratio (aOR) = 1.48, 95% confidence interval (CI): 1.04–2.11], no fear of adverse effects (aOR = 4.25, 95%CI: 2.77–6.53), perceived susceptibility of children to HFMD (aOR = 2.15, 95%CI: 1.42–3.25) and children not previously diagnosed with HFMD (aOR = 1.56, 95%CI: 1.07–2.27) were positively associated with EV71 vaccination acceptability. However, parental education background (aOR = 0.54, 95%CI: 0.37–0.80) was negatively correlated with vaccination acceptability. Our study provides baseline information for future vaccination campaigns to help improve the EV71 vaccine uptake rate. Special efforts are urgently needed to improve the awareness and knowledge of EV71 vaccines in China. 相似文献
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目的 了解嘉善县5岁以下儿童监护人对肠道病毒71型(EV71)疫苗的接种意愿,分析其影响因素,为制定疫苗接种和疫情防控策略提供依据.方法 在嘉善县所有接种门诊接种现场随机选取5岁以下儿童监护人进行统一问卷调查.结果 共调查854名监护人,其中488名监护人(57.14%)愿意为孩子接种EV71疫苗,366名监护人(42.86%)不愿意为孩子接种EV71疫苗;调查儿童中有54名(6.32%)曾患过手足口病.监护人文化程度越高(x2趋势=7.59,P<0.01)、年收入越高(x2趋势=13.31,P<0.01)越愿意为孩子接种EV71疫苗.儿童监护人性别为男性(OR=1.38,95%CI:1.04~1.85)、听说过EV71疫苗(OR=1.51,95%CI:1.15~1.99)、孩子曾患过手足口病(OR =4.66,95%CI:2.17~9.99)是愿意为孩子接种EV71疫苗的保护因素.监护人不愿意接种的主要原因为担心疫苗安全性和不良反应(45.63%)、担心疫苗保护效果(26.78%)和疫苗价格太高(17.76%).结论 嘉善县儿童监护人对EV71疫苗的接种意愿不高,今后应加强EV71疫苗和手足口病相关知识的健康教育,提高家长对疾病的认识,消除在疫苗安全性与接种效果等方面的顾虑,提高疫苗接种率. 相似文献
10.
《Vaccine》2015,33(43):5779-5785
Noroviruses are the main cause of severe viral gastroenteritis, which results in estimated 200,000 deaths each year, primarily in children in the developing world. Genogroup II.4 (GII.4) strains are responsible for the majority of norovirus outbreaks. Enterovirus 71 (EV71), the leading causative agent of hand, foot and mouth disease, has recently been prevalent in Asia-Pacific regions, resulting in significant morbidity and mortality in young children. However, no vaccine is commercially available for either norovirus GII.4 or EV71. Recombinant virus-like particles (VLPs) derived from either GII.4 or EV71 have been shown to be promising monovalent vaccine candidates. In this study, we investigate the possibility to formulate a VLP-based bivalent vaccine for both norovirus GII.4 and EV71. The GII.4- and EV71-VLPs were produced in a baculovirus-insect cell expression system. A bivalent combination vaccine comprised of GII.4 and EV71 VLPs was formulated and compared with monovalent GII.4- and EV71-VLPs for their immunogenicity in mice. We found that the bivalent vaccine elicited durable antibody responses toward both GII.4 and EV71, and the antibody titers were comparable to that induced by the monovalent vaccines, indicating there is no immunological interference between the two antigens in the combination vaccine. More significantly, the bivalent vaccine-immunized mouse sera could efficiently neutralize EV71 infection and block GII.4-VLP binding to mucin. Together, our results demonstrate that the experimental combination vaccine comprised of GII.4 and EV71-VLPs is able to induce a balanced protective antibody response, and therefore strongly support further preclinical and clinical development of such a bivalent VLP vaccine targeting both norovirus GII.4 and EV71. 相似文献
11.
《Vaccine》2019,37(31):4344-4353
BackgroundHand, foot and mouth disease (HFMD), especially that caused by enterovirus 71 (EV71) infection, is a public health concern in the Asia-Pacific region. We report a phase I clinical trial of an EV71 candidate vaccine (INV21) based on a binary ethylenimine inactivated B2 sub-genotype formulated with aluminum hydroxide.MethodsIn this double-blind, placebo-controlled, randomized, dose escalation study adult volunteers received two vaccinations 28 days apart of low or high dose formulations of the candidate vaccine and were then monitored for safety and reactogenicity for four weeks after each dose, and for their immune responses up to 28 weeks.ResultsOf 36 adults enrolled, 35 completed the study as planned. Either no or mild adverse events were observed, mainly injection site pain and tiredness. Seroconversion was 100% after two vaccinations. High geometric mean neutralizing antibody titers (GMT) were observed 14 days post first dose, peaking 14 days post second dose (at Day 42) in both high and low dose groups; GMTs on days 14, 28, 42, and 56 were 128, 81, 323, 203 and 144, 100, 451, 351 in low- and high-dose groups, respectively. Titers for both doses declined gradually to Day 196 but remained higher than baseline and the placebo groups, which had low GMTs throughout the duration of the study. Cross-neutralizing antibody activity against heterologous sub-genotypes was demonstrated.ConclusionThese data show that the EV71 candidate vaccine is safe and immunogenic in adults and supports further clinical development as a potential pediatric vaccine by initiating a dose-escalation study for determining the dose-dependent safety and immunogenicity of the vaccine in young naïve children. 相似文献
12.
Enterovirus 71 (EV71) and coxsackievirus A16 (CA16) are the two major causative agents of hand, foot and mouth disease (HFMD), which is an infectious disease frequently occurring in children. A bivalent vaccine against both EV71 and CA16 is highly desirable. In the present study, we compare monovalent inactivated EV71, monovalent inactivated CA16, and a combination vaccine candidate comprising of both inactivated EV71 and CA16, for their immunogenicity and in vivo protective efficacy. The two monovalent vaccines were found to elicit serum antibodies that potently neutralized the homologous virus but had no or weak neutralization activity against the heterologous one; in contrast, the bivalent vaccine immunized sera efficiently neutralized both EV71 and CA16. More importantly, passive immunization with the bivalent vaccine protected mice against either EV71 or CA16 lethal infections, whereas the monovalent vaccines only prevented the homologous but not the heterologous challenges. Together, our results demonstrate that the experimental bivalent vaccine comprising of inactivated EV71 and CA16 induces a balanced protective immunity against both EV71 and CA16, and thus provide proof-of-concept for further development of multivalent vaccines for broad protection against HFMD. 相似文献
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目的 了解肠道病毒71型(EV71)疫苗接种行为及其与接种意愿差异的影响因素,以更好地发挥该疫苗的作用。方法 在广东省广州市海珠区选取5个街道,于2016年6月在各街道接种门诊共选取1 483名6~35月龄儿童家长进行基线调查,其中1 113名于EV71疫苗投入使用约4个月后完成了随访调查,分析疫苗接种及其与接种意愿差异的影响因素。结果 基线调查、随访调查的愿意接种率分别为81.39%、83.47%;1 113名随访调查者EV71疫苗接种率为67.30%,与接种意愿差异有统计学意义(χ2=78.433,P=0.000)。家长认为疫苗安全或不清楚是否安全、认为疫苗可以≥70%或不确定多大概率预防手足口病以及听从接种医生的安排或建议是家长让儿童接种EV71疫苗的有利因素(P<0.05);而儿童有手足口病史、较清楚EV71病毒与手足口病关系的家长则倾向于不让儿童接种EV71疫苗(P<0.05)。对愿意接种者而言,认为疫苗安全或不清楚是否安全(OR很安全vs不安全=5.264,OR一般vs不安全=3.757,OR不清楚vs不安全=1.582)是促使其将意愿转变为实际接种的因素,而认为疫苗价格较贵(OR贵vs便宜=0.543)、较清楚EV71病毒与手足口病关系(OR清楚vs不清楚=0.544,OR部分清楚vs不清楚=0.731)则是阻碍其将意愿付诸行动的因素;对不愿接种者而言,听从接种医生的安排或建议(OR很大程度vs很小程度=3.074,OR一般程度vs很小程度=1.836)以及受朋友等其他人的影响较大(OR很大程度vs很小程度=2.445)是促使其意愿转变并最终接种疫苗的因素,而清楚EV71病毒与手足口病关系(OR清楚vs不清楚=0.416)则是使其坚持意愿不接种疫苗的因素。结论 家长对EV71疫苗效果、安全性及EV71病毒与手足口病关系的认识以及接种医生的安排或建议是影响EV71疫苗接种的重要因素。 相似文献
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《Vaccine》2017,35(30):3709-3717
Enterovirus 71 (EV71) and Coxsackievirus A16 (CVA16) are the two major causative agents of hand, foot and mouth disease (HFMD), which erupts in the Asia-Pacific regions. A bivalent vaccine against both EV71 and CVA16 is highly desirable. In the present study, on the bases that an experimental bivalent vaccine comprising of inactivated EV71 and CVA16 induces a balanced protective immunity against both EV71 and CVA16, we compare the immunogenicity and reactogenicity of one fourth of a full dose of an intradermal vaccine administered by needle-free liquid jet injector with a full dose of an intramuscular vaccine administered by needle-syringe in monkeys. The results suggest that intradermal injection of a fractional dose of an inactivated HFMD vaccine elicits similar immunogenicity and reactogenicity to intramuscular inoculation of a full dose of an Al(OH)3-adjuvanted vaccine, regardless of whether monovalent or bivalent vaccines were used. Our results support the use of an intradermal bivalent vaccine strategy for HFMD vaccination in order to satisfy the requirements and reduce the costs. 相似文献
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目的了解幼托儿童家长对手足口病(EV71)疫苗相关认知、子女接种情况及影响因素,为做好疫苗的接种工作提供科学依据。方法采用现况调查(普查)的方法对上海市浦东新区东明社区辖区内全部12所幼儿园的2 783名幼儿家长进行问卷调查,分析幼儿家长对EV71疫苗的相关认知及疫苗接种的影响因素。结果有1 843名儿童家长调查前听说过EV71疫苗,家长对EV71疫苗的总体知晓率为51.9%,EV71疫苗相关信息的主要获取途径有887名为医院,其次有752名通过学校获得。接种了EV71疫苗的儿童有1 014名,选择接种EV71疫苗的主要原因是认为疫苗可以有效预防手足口病(76.1%),未接种EV71疫苗的主要原因是不知道有预防手足口病的疫苗(31.7%)。有2 478名儿童家长认为应该将EV71疫苗纳入计划免疫范畴里。多因素Logistic回归分析显示,学校为公办(OR=0.72,95%CI=0.59~0.89)、母亲户籍为本市(OR=0.76,95%CI=0.64~0.90)、对EV71疫苗不知晓(OR=0.42,95%CI=0.35~0.49)及家长认为EV71疫苗价格高(OR=0.66,95%C... 相似文献
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《Vaccine》2020,38(32):4917-4923
Enterovirus A71 (EV71) is one of the major causative agents of hand, foot and mouth disease (HFMD), and is sometimes associated with severe central nervous system syndromes. Vaccines against EV71 infection have been developed or are in development in several countries and few have been licensed in China. In response to requests from some of these countries, WHO convened a working group meeting in Shanghai China from 11 to 12 September 2019 to develop WHO Recommendations to assure the quality, safety and efficacy of EV71 vaccines. Meeting participants included members of the drafting group, experts from vaccine developers, manufacturers, regulators and academia. The epidemiology of EV71, as well as the development, regulation and standardization of EV71 vaccines were reviewed in the meeting. Information on R&D, manufacturing, quality control and standardization of EV71 vaccines was presented by vaccine developers, manufacturers and regulators. Based on their experience, the working group discussed the main principles that would determine WHO’s position on quality, safety and efficacy of EV71 vaccines. The working group agreed to develop WHO Recommendations to assure the quality, safety and efficacy of inactivated EV71 vaccines with a scope covering only whole virus inactivated vaccines. Other type of vaccines, such as EV71 virus-like particles (VLPs) will not be covered as they are still at the developmental stage. The outline of the document was agreed and will follow the usual style of WHO recommendations. It was also agreed to submit the draft Recommendations for review and adoption to the WHO ECBS in 2020 following discussion at a WHO informal consultation, which will include NRAs and vaccine manufacturers. 相似文献
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Aristine Cheng Chang-Phone Fung Chia-Chyi Liu Yi-Tsung Lin Hsih-Yeh Tsai Shan-Chwen Chang Ai-Hsiang Chou Jui-Yuan Chang Ren-Huei Jiang Yi-Chin Hsieh Ih-Jen Su Pele Choi-Sing Chong Szu-Min Hsieh 《Vaccine》2013
Background
Large-scale outbreaks of enterovirus 71 (EV71) infections have occurred in Asia-Pacific regions. Severe complications include encephalitis and poliomyelitis-like paralysis, cardiopulmonary collapse, and death, necessitating an effective vaccine against EV71.Methods
In this randomized Phase I study, we evaluated the safety and immunogenicity of an inactivated alum-adjuvanted EV71 whole-virus vaccine produced on Vero cell cultures. Sixty healthy volunteers aged 20–60 years received two doses of vaccine, administered 21 days apart. Each dose contained either 5 μg of EV71 antigen with 150 μg of adjuvant (Group A05) or 10 μg of EV71 antigen with 300 μg of adjuvant (Group B10). Serologic analysis was performed at baseline, day 21, and day 42.Results
There were no serious adverse events. Mild injection site pain and myalgia were the most common adverse events with either vaccine formulation. The immunogenicity data showed that 90% of vaccine recipients have a 4-fold or greater increase in neutralization antibody titers (NT) after the first dose, without a further increase in NT after the second dose. The seroconversion rates on day 21 and day 42 were 86.7% and 93.1% respectively, in Group A05, and 92.9% and 96.3%, respectively, in Group B10. Thus, 5 μg and 10 μg of the EV71 vaccine can induce a remarkable immune response in healthy adults after only the first vaccination.Conclusion
The 5 μg and 10 μg adjuvanted EV71 vaccines are generally safe and immunogenic in healthy adults. (ClinicalTrials.gov number, NCT01268787). 相似文献20.
Formaldehyde-inactivated human enterovirus 71 vaccine is compatible for co-immunization with a commercial pentavalent vaccine 总被引:1,自引:0,他引:1
In this study we tested the effectiveness of a formaldehyde-inactivated EV71 vaccine and its compatibility for co-immunization with a pentavalent vaccine that contained inactivated poliovirus (PV) vaccine. The inactivated EV71 vaccine (C2 genogroup) elicited an antibody response which broadly neutralized homologous and heterologous genogroups, including B4, C4, and B5. Pups from vaccinated dams were resistant to the EV71 challenge and had a high survival rate and a low tissue viral burden when compared to those from non-vaccinated counterparts. Co-immunization with pentavalent and inactivated EV71 vaccines elicited antibodies against the major components of the pentavalent vaccine including the PV, Bordetella pertussis, Haemophilus influenzae type b, diphtheria toxoid, and tetanus toxoid at the same levels as in mice immunized with pentavalent vaccine alone. Likewise, EV71 neutralizing antibody titers were comparable between EV71-vaccinated mice and mice co-immunized with the two vaccines. These results indicate that formaldehyde-inactivated whole virus EV71 vaccine is feasible for designing multivalent vaccines. 相似文献