河南省2014年手足口病重症病例病原学分析

目的 分析2014年河南省手足口病(HFMD)重症病例病原学特征。方法 整群抽取郑州市某儿童医院2014年4-6月244例HFMD住院病例作为研究对象,采集粪便标本,病原学检测采用荧光定量RT-PCR、病毒分离、VP1测序比对等方法。病原学特征统计分析采用SPSS 17.0软件。结果 244例手足口病病例中,重症组109例,轻症组135例,肠道病毒(EV)通用引物RT-PCR阳性229例,阳性率为93.85%。肠道病毒71型(EV71)、柯萨奇病毒A组16型(Cox A16)和Cox A10的感染构成比分别为83.84%、5.68%和8.30%。EV71感染致8例心肺功能衰竭,2例死亡;Cox A10感染致1例心肺功能衰竭、死亡。重症组与轻症组之间肠道病毒感染率差异有统计学意义(χ²=5.312,P=0.021)。采用Fisher精确概率法对重症组和轻症组EV71、Cox A16和其他EV感染构成比进行统计学比较,P=0.048。EV71和Cox A10感染致心肺功能衰竭发生率和致死率的差异无统计学意义(分别为χ²=0.051,P=0.821和χ²=2.198,P=0.138)。2014年河南省Cox A10分离株属于基因6型,VP1区段核苷酸和氨基酸同源性分别为94.3%~99.7%和96.3%~100.0%。结论 EV71仍然是河南省HFMD的主要病原。Cox A10在感染病原谱中所占比加大,且感染后可致心肺功能衰竭,应加强对其他EV的监测。     

湖南省安化县2013-2016年手足口病住院负担估计

目的 估计2013年10月至2016年9月湖南省安化县各血清型及分年龄组的手足口病住院负担。方法 收集6家病毒学监测医院的儿童手足口病住院记录及23家乡镇卫生院的手足口病新农合报销记录,估计安化县分年龄组的手足口病住院负担。结合病毒学监测结果,估计各血清型肠道病毒（EV）相关的手足口病住院负担。结果 共纳入手足口病住院病例3 541例,其中实验室确诊病例数为3 146例。仅有1例为手足口病重症,其余均无并发症。临床诊断和实验室确诊手足口病平均住院率分别为723/10万（95% CI：699/10万~747/10万）和642/10万（95% CI：620/10万~665/10万）。柯萨奇病毒（Cox）A组16型（Cox A16）（208/10万）和6型（Cox A6）（202/10万）相关的手足口病住院率高于EV71（130/10万）、Cox A10（38/10万）和其他EV（64/10万）,差异有统计学意义（P<0.001）。手足口病住院率在1岁组最高（3 845/10万）,之后随年龄增长住院率逐渐降低。与EV71和Cox A16相比,Cox A6相关的手足口病住院率表现出低年龄特点（P<0.001）。结论 湖南省安化县轻症手足口病住院负担严重,尤其在低年龄组儿童中,且主要由EV71、Cox A16、Cox A6和Cox A10导致。     

肠道病毒71型与柯萨奇病毒16型病原体检测在手足口病流行中的意义

目的探究肠道病毒71型(EV71)和柯萨奇病毒16型(Cox A16)病原体RT-PCR检测在预防手足口病传播中的意义。方法对70例疑似手足口病患儿和30例健康儿童的粪便进行EV71和Cox A16及肠道病毒(EV)RT-PCR检测。结果 70例有发热、口腔黏膜疹、手足皮疹的患儿粪便中EV病毒全阳性,EV71病毒阳性25例占35.71%,Cox A16病毒阳性22例占31.43%,二者均阳性的10例占14.29%,30例体检儿童粪便中EV病毒阳性5例,EV71和Cox A16全阴性。结论手足口病以EV71和Cox A16病原体感染为主,检测EV71和Cox A16病原体可以早期诊断手足口病,对预防和治疗手足口病具有重要临床意义。     

北京地区不同人群柯萨奇病毒A16型和肠道病毒71型感染状况调查

目的 了解北京地区不同人群柯萨奇病毒A16型（coxsachievirus A16,CoxA16）和肠道病毒71型（enterovirus 71,EV71）感染状况。方法 2012年对北京9区进行整群随机抽样,采集血样,开展血清流行病学调查。用酶联免疫吸附实验检测血清中抗CoxA16和抗EV71 免疫球蛋白G（immunoglobulin G,IgG）和免疫球蛋白M（immunoglobulin M,IgM）抗体。结果 2 140名被研究人群中,抗EV71 IgG和IgM阳性率分别为27.0%和1.6%,抗CoxA16 IgG和IgM的阳性率分别为48.5%和4.2%,抗EV71 IgM与抗CoxA16 IgM同时阳性阳性率为0.7%,抗EV71 IgG与抗CoxA16 IgG同时阳性阳性率为17.2%。各年龄组抗EV71 IgM、IgG阳性率、抗CoxA16 IgM、IgG阳性率、抗EV71 IgM 和抗CoxA16 IgM同时阳性的阳性率、抗EV71 IgG和抗CoxA16 IgG同时阳性阳性率差异均有统计学意义（均有P<0.05）。1～岁组抗EV71 IgM阳性率最高,5～岁组抗CoxA16 IgM阳性率最高,10～岁组抗EV71IgG 和20～岁组抗CoxA16 IgG阳性率最高。女性抗CoxA16 IgG阳性率高于男性。结论 低龄组儿童是手足口病防控的重点人群,手足口病防控措施制定应考虑地域分布因素。     

浙江省宁波市2008-2011年手足口病流行病学及病原学特征分析

目的 <\b>分析2008-2011年宁波市手足口病流行特征.方法 <\b>从疾病监测信息报告管理系统获取宁波市2008-2011年手足口病资料,运用描述流行病学方法进行分析.对粪便标本采用RT-PCR扩增基因序列测定,并利用生物学软件分析.结果 <\b>2008-2011年宁波市共报告手足口病病例37 524例,其中重症196例,死亡12例,年均发病率为145.26/10万,病死率为0.03％.＜5岁儿童占报告病例的95.89％,散居儿童占64.10％;各地区发病均处于较高水平,其中宁海、象山县为发病率最高的地区,发病高峰在4-7月,男性多于女性.实验室确诊2394例,肠道病毒(EV)71型是主要的病毒株,进化树分析表明宁波市手足口病EV71分离株属于C4a进化分支,其流行和传播存在多个传播链.Cox A16株同时包含Bla和Bib两条进化分支共同流行.健康儿童EV71中和抗体阳性率为53.48％,GMT为11.23(8.33 ～ 14.98);Cox A16中和抗体阳性率为63.18％,GMT为12.61(6.70 ～ 16.52).结论 <\b>宁波市手足口病疫情处于高流行态势,＜5岁散居儿童是主要发病人群,EV71为优势株;EV71毒株为C4a亚群,CoxA16毒株为B1基因亚型,与中国大陆优势株流行趋势一致.     

我国2015－2016年哨点监测手足口病病原学和并发症分析

目的 分析2015－2016年我国手足口病哨点监测系统的手足口病特征,探讨建立手足口病哨点监测的可行性、优势及不足。方法 数据来源于11个国家级哨点监测点2015年11月至2016年10月手足口病监测数据,描述手足口病的病原特征、代表性和重症病例并发症情况,采用多因素logistic回归分析手足口病哨点监测样本阳性率的相关影响因素。采用SPSS 20.0软件进行统计学分析。结果 共有4 783例手足口病病例样本,其中轻症病例3 390例,重症病例1 390例,死亡3例。肠道病毒（EV）阳性率为81.43%（3 895/4 783）,轻症病例优势血清型为其他EV（52.68%,1 482/2 813）,重症病例优势血清型为EV71（65.31%,706/1 081）。哨点监测显示的优势血清型与同时期现有监测血清型基本一致。其他EV所致病例中低年龄组儿童所占比例高于EV71和柯萨奇病毒A组16型（Cox A16）（χ²=130.17,P<0.001）。多因素logistic回归结果显示,样本阳性率高与男性、高发月份病例、儿童医院病例、样本为粪便、及时采样有关。不同类型样本阳性率均呈现随发病-采样间隔时间的延长而下降的趋势（粪便趋势χ²=14.47,P<0.001;咽拭子趋势χ²=31.99,P<0.001;肛拭子趋势χ²=24.26,P<0.001）。无菌性脑膜炎、非脑干脑炎、脑干脑炎为重症病例最常见的3种并发症,EV71和其他EV所致重症病例并发症差异无统计学意义。结论 哨点监测发现性别、发病月份、接诊医院类别、标本类型、采样及时性是影响手足口病样本阳性率的5个独立影响因素。哨点监测可以收集这些影响因素以提升监测质量。设立手足口病国家级哨点监测在我国是可行的。     

2008年-2010年湖州市手足口病病原监测分析

目的:了解湖州市手足口病的感染情况,为制定预防和控制措施提供科学依据。方法:采用荧光定量RT-PCR方法,对2008年-2010年湖州市765份疑似手足口病感染者的疱疹液、咽拭子及粪便标本进行肠道病毒、肠道病毒71型和柯萨奇病毒A16型的核酸检测。结果:肠道病毒通用核酸阳性510例,阳性率为66.67%(510/765)。其中EV71阳性228例,阳性率为29.80%(228/765);Cox A16阳性134例,阳性率为17.52%(134/765);其他EV病毒阳性148例,阳性率为19.35%(148/765)。男女阳性率分别为67.46%(313/464)和65.44%(197/301)。5岁以下年龄组儿童阳性率为67.64%,是感染的主要人群。结论:EV71是引起湖州市儿童手足口病的主要病原,不同性别间EV、EV71及Cox A16的发病率无显著性差异。定期开展手足口病病原学监测,将有助于提出更好的预防和控制措施。     

实时荧光定量PCR检测手足口病肠道病毒71型与柯萨奇病毒16型临床分析

目的 探讨肠道病毒71型(EV71)与柯萨奇病毒A 16型(Cox A16)实时荧光定量PCR检测在早期诊断手足口病(HFMD)中的意义,为临床治疗提供参考依据。方法 对2012年3月-2013年6月157例疑似HFMD患儿的粪便、疱疹液、鼻咽拭子样本进行EV71、Cox A16、肠道病毒(EV)的实时荧光定量PCR检测,根据试剂说明书的标准判定;采用SPSS16.0进行数据分析。结果 粪便中EV、EV71、Cox A16的检出率分别为94.09%、42.04%、38.85%,高于鼻咽拭子样本,差异有统计学意义(P<0.05);而粪便与疱疹液中EV、EV71、Cox A16的阳性率相比,差异无统计学意义。结论 对HFMD患儿早期诊断、早期治疗,应该首选粪便标本采用实时荧光定量PCR法检测EV、EV71、Cox A16。     

广东省2012-2016年柯萨奇病毒A组16型感染手足口病病例流行特征分析

目的 了解2012－2016年广东省柯萨奇病毒A组16型（Cox A16）感染手足口病病例流行特征。方法 在广东省8个城市共选取8家哨点医院开展手足口病普通病例Cox A16感染监测，结合手足口病个案及暴发数据，估算Cox A16感染手足口病发病情况并分析人群和时间分布特征。结果 ①广东省Cox A16感染手足口病估算发病率以2014年（113.0/10万）最高，其次为2016年（86.4/10万）、2012年（79.1/10万）；2015年（29.0/10万）和2013年（28.8/10万）较低。②暴发以Cox A16感染（54.6%，89/163）为主，高流行年份年均暴发数（28起）是低流行年份（2.5起）的11.2倍。③估算发病率随年龄升高呈下降趋势（趋势χ²=853 905.63，P<0.01），高发年龄组依次为1～（1 449.2/10万）、3～（1 097.0/10万）、2～（1 083.5/10万）、4～（687.8/10万）和0～岁（604.9/10万）；随月龄增加呈上升趋势（趋势χ²=5 541.77，P<0.01），高发月龄依次是11～（2 105.1/10万）、10～（1 448.6/10万）、9～（938.3/10万）、8～（703.3/10万）和6～月龄（664.6/10万）。④高发月份是5月（143.9/10万）和6月（131.5/10万）。结论 2012－2016年广东省Cox A16感染手足口病在各年份流行强度不同；Cox A16感染水平高时，暴发疫情增多，主要发生在托幼机构，5－6月常见，0～4岁儿童是Cox A16感染手足口病高危人群，6～11月龄为高发月龄。     

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。     

EV71抗原检测方法的建立及初步临床应用

目的建立EV71抗原双抗体夹心检测方法,并初步探讨其在临床血清样品检测中的应用。方法用抗EV71病毒单克隆抗体包被酶联反应板,加入待检标本反应后,用HRP标记的抗EV71病毒单克隆抗体进行检测,建立EV71抗原双抗体夹心检测方法;采用抗人IgM单克隆抗体包被96孔酶联板,辣根酶标记的EV71抗原,建立ELISA捕获方法检测抗EV71-IgM。2种方法同时检测230份体检人员血清,确定方法的cut-off(CO)值,并检测140份手足口病患者血清,采用Graraph Pad Prism 4软件作图并绘制ROC曲线。结果EV71抗原检测方法的CO值为0.168,抗EV71-IgM ELISA检测方法的CO值为0.173。在140例手足口病患者血清中,EV71抗原检测方法的阳性检出率为45.00%,抗EV71-IgM ELISA检测方法的阳性检出率为42.86%,其中共同阳性患者45例,单独EV71抗原阳性患者18例,单独抗EV71-IgM抗体阳性患者15例,如果2种方法联合检测,其阳性检出率可提高到55.71%。结论ELISA检测EV71抗原诊断HFMD具有很好的准确性,结合EV71-IgM抗体捕获检测技术,可进一步提高灵敏度,具有很好的临床应用前景。     

广东省健康人群手足口病病原隐性感染状况调查

目的 了解广东省健康人群手足口病病原隐性感染情况.方法 在广东省7个市随机抽取7个年龄组健康儿童及成年人,采集粪便标本进行手足口病病原检测.结果 7个市共采集1285份样本,肠道病毒71型(EV71)阳性率为0.39％(5/1285),柯萨奇病毒A组16(CA16)阳性率为0.23％(3/1285),其他肠道病毒阳性率为7.00％ (90/1285).4～6岁年龄组EV71阳性率最高,为1.79％ (4/223),其次为0～3岁年龄组,为0.67％(1/223),其余年龄组均未检出EV71;只有4～6岁年龄组检出CA16,阳性率为1.35％ (3/223).所有EV71阳性标本均在本地户籍人群中检出,阳性率为0.47％(5/1063);CA16在本地户籍人群(0.19％)和外地户籍(0.85％)中均有检出,差异无统计学意义(P＞0.05).农村和城市EV71的阳性率分别为0.36％和0.54％,差异无统计学意义(P＞0.05);所有CA16阳性标本均在城市儿童中检出.结论 广东省健康人群中仅6岁以下年龄组检出EV71和CA16阳性,健康成年人中未检出EV71和CA16阳性,应重点对儿童尤其是学龄前儿童采取有效防控措施.     

CA6阳性与EV71、CA16阳性手足口病患儿临床特征分析

目的 分析柯萨奇病毒A6型(CA6)阳性与肠道病毒71型(EV71)、柯萨奇病毒A16型(CA16)阳性手足口病患儿的临床特征.方法 选取商洛市中心医院2014年1月至2016年12月收治的1528例手足口病患儿,通过实时荧光定量聚合酶链反应法检测患儿肠道病毒核酸,以分析CA6、EV71、CA16三种病毒引起的手足口病患儿的临床特征.结果 在1528例手足口病患儿中,经病原学确诊出374例CA6阳性患儿、673例CA16阳性患儿、481例EV71阳性患儿.CA6阳性患儿发病平均年龄(t值分别为6.34、5.85)、齿龈部疱疹分布(χ2值分别为5.65、5.23)均低于CA16、EV71阳性患儿(均P<0.05),且发热分布均高于CA16、EV71阳性患儿(χ2值分别为8.56、8.23,均P<0.05).CA6阳性患儿C反应蛋白和WBC升高分布均高于CA16、EV71阳性患儿(χ2值分别为5.34、5.89;6.34、6.83,均P<0.05).结论 CA6已发展成一种手足口病患儿新型的流行病原,且其临床特征与因EV71及CA16引起的手足口病有所不同,可作为临床诊断的依据.     

Low sensitivity of rapid tests detecting anti-CoV-2 IgG and IgM in health care workers’ serum for COVID-19 screening

Background: the sensitivity and specificity of a rapid antibody test were investigated for the screening of healthcare workers. Methods: the serum of 389 health care workers exposed to COVID-19 patients or with symptoms, were analysed. All workers underwent monthly the screening for SARS-CoV-2 with detection of viral RNA in nasopharyngeal swabs by RT-PCR. IgG antibody detection in serum was performed by Chemiluminescence Immunoassay (CLIA) and by the Rapid test (KHB diagnostic kit for SARS CoV-2 IgM/IgG antibody after a median of 7.6 weeks (25°-75° percentiles 6.6-11.5). Results: the rapid test resulted positive in 31/132 (23.5%), 16/135 (11.8%) and 0/122 cases in COVID-19 positive individuals, in those with only SARS-CoV-2 IgG antibodies and in those negative for both tests, respectively. Sensitivity was 17.6% (CI95% 13.2-22.7) and 23.5% (CI95% 16.5-31.6), and specificity was 100% (CI95% 97-100) and 100% (CI95% 97-100) considering Rapid test vs CLIA IgG or Rapid test vs SARS-CoV-2 positive RNA detection, respectively. Conclusion: the KHB Rapid test is not suitable for the screening of workers with previous COVID-19 infection.     

Measles and rubella immunity in the population of Bhutan, 2017

BackgroundIn 2017, measles elimination was verified in Bhutan, and the country appears to have sufficiently high vaccination coverage to achieve rubella elimination. However, a measles and rubella serosurvey was conducted to find if any hidden immunity gaps existed that could threaten Bhutan’s elimination status.MethodsA nationwide, three-stage, cluster seroprevalence survey was conducted among individuals aged 1–4, 5–17, and >20 years in 2017. Demographic information and children’s vaccination history were collected, and a blood specimen was drawn. Serum was tested for measles and rubella immunoglobulin G (IgG). Frequencies, weighted proportions, and prevalence ratios for measles and rubella seropositivity were calculated by demographic and vaccination history, taking into account the study design.ResultsOf the 1325 individuals tested, 1045 (81%, 95% CI 78%–85%) were measles IgG seropositive, and 1290 (97%, 95% CI 95%–99%) were rubella IgG seropositive. Rubella IgG seropositivity was high in all three age strata, but only 47% of those aged 5–17 years were measles IgG seropositive. Additionally, only 41% of those aged 5–17 years who had documented receipt of two doses of measles– or measles-rubella–containing vaccine were seropositive for measles IgG, but almost all these children were rubella IgG seropositive.ConclusionsAn unexpected measles immunity gap was identified among children 5–17 years of age. It is unclear why this immunity gap exists; however, it could have led to a large outbreak and threatened sustaining of measles elimination in Bhutan. Based on this finding, a mass vaccination campaign was conducted to close the immunity gap.     

Interchangeability of two Enterovirus 71 inactivated vaccines in Chinese children: A phase IV,open-label,and randomized controlled trial

BackgroundIn China, three inactivated Enterovirus 71 (EV71) vaccines have been approved. Although the vaccines in an immunization series should be from a single manufacture, children sometimes have to receive EV71 vaccines from more than one manufacturers. The aim of this study was to evaluate the interchangeability and safety of vaccination with EV71 vaccines from two manufacturers among Chinese children.MethodsWe conducted an open label and randomized controlled study among children aged 6–35 months from November 2018 to January 2019. The participants were randomly assigned (1:1:1:1) to receive EV71 vaccines in one of the four different schedules (two using a single vaccine for all doses from one manufacture, and two mixed schedules using vaccines from two manufactures). Blood samples were collected pre-vaccination (Day 0) and one month after the second dose (Day 60) for neutralizing antibody assay. Immunogenicity was assessed in the per-protocol cohort and safety was assessed in the total vaccinated cohort.ResultsA total of 300 children were enrolled and randomized, of whom 89.0% (267/300) were included in the per-protocol cohort for immunogenicity analysis. The seroconversion rates of the EV71 neutralizing antibody in four groups ranged from 98.4% to 100.0%, and were not significantly different among the groups. Compared with other groups, geometric mean titer was higher in group D, in which the participants received Institute of Medical Biology Chinese Academy of Medical Sciences (CAMS) vaccine in the first dose and the Sinovac vaccine in the second dose. Safety profiles were similar among the four groups and no serious adverse events related to the vaccination were reported.ConclusionsInterchangeability of EV71 vaccines from two manufactures to complete an immunization series showed good immunogenicity and safety. The antibody response levels may vary by vaccination sequences of EV71 vaccines from the two manufacturers.Trial registration: ClinicalTrials.govNCT03873740.     

Impact of publicly available vaccination rates on parental school and child care choice

ObjectiveSeveral states require schools and child cares to report vaccination rates, yet little is known about the impact of these policies. Our objectives were to assess: (1) predicted impact of vaccination rates on school/child care choice, (2) differences between vaccine hesitant and non-hesitant parents, and (3) differences by child’s age.MethodsIn 2016, a cross-sectional email survey of Colorado mothers with children ≤12 years old assessed value of vaccination rates in the context of school/child care choice. A willingness-to-pay framework measured preference for schools/child cares with different vaccination rates using tradeoff with commute time.ResultsResponse rate was 42% (679/1630). Twelve percent of respondents were vaccine hesitant. On a scale where 1 is “not important at all” and 4 is “very important” parents rated the importance of vaccination rates at 3.08. Respondents (including vaccine-hesitant respondents) would accept longer commutes to avoid schools/child cares with lower vaccination rates. Parents of child-care-age children were more likely to consider vaccination rates important.ConclusionsThis study shows parents highly value vaccination rates in the context of school and child care choice. Both hesitant and non-hesitant parents are willing to accept longer commute times to protect their children from vaccine-preventable diseases.     

微量细胞病变法检测健康人群EV71和CVA16中和抗体水平

目的了解深圳市福田区健康人群中肠道病毒71型(EV71)和柯萨奇A16型(CVA16)隐性感染情况。方法应用微量细胞病变法,对2011年和2012年一般人群流感抗体水平调查采集的471份血清标本进行EV71和CVA16中和抗体检测,并对检测结果进行统计学分析。结果 471份健康人群血清中EV71和CVA16中和抗体阳性率分别为25.50%和33.10%;EV71抗体由0～岁组的7.14%上升至15～岁组的42.65%(χ2=42.12,P<0.01),上升5.97倍,抗体几何平均滴度(GMT)呈缓慢上升趋势;CVA16抗体由0～岁组的9.18%上升至5～岁组的58.73%(χ2=61.87,P<0.01),上升6.39倍,抗体GMT呈波峰状;各年龄组两种抗体混合感染阳性率为11.25%(χ2=64.95,P<0.01)。结论本地区健康人群中存在肠道病毒隐性感染,各年龄组CVA16抗体阳性率均高于EV71;5～25年龄人群EV71和CVA16中和抗体阳性率、GMT和混合感染情况均高于其他年龄组,应加强5～25年龄人群的流行病学监测。     

Chimeric enterovirus 71 virus-like particle displaying conserved coxsackievirus A16 epitopes elicits potent immune responses and protects mice against lethal EV71 and CA16 infection

Hand-foot-and-mouth disease (HFMD) is an infectious disease of infants and young children frequently caused by the enterovirus A species, mainly enterovirus 71 (EV71) and coxsackievirus A16 (CA16). In this study, we prepared the EV71 virus-like particle (EV71-VLP) and its chimeras using recombinant baculovirus (Bac-P1-3CD) co-expressing EV71 P1 (under polyhedrin promoter) and 3CD (under CMV-IE promoter) proteins in Sf9 cells. EV71-VLP chimera ChiEV71(1E)-VLP or ChiEV71(4E)-VLP displayed single CA16 PEP71 epitope in VP1 or four conserved CA16 neutralizing epitopes (PEP71 in VP1, aa136-150 in VP2, aa176-190 in VP3 and aa48-62 in VP4) by substitution of the corresponding regions of EV71 structure proteins, respectively. In mice, EV71-VLP and its chimeras elicited similar EV71-specific IgG and neutralizing antibody (NAb) titers compared to inactivated EV71. Expectedly, vaccination of ChiEV71(1E)-VLP or ChiEV71(4E)-VLP resulted in significantly increased CA16-specific IgG and NAb production and improved cross-protection against CA16 infection compared to EV71-VLP. Interestingly, the VLPs induced potent cellular immune responses and significantly decreased Th2 type (IL-4 and IL-10) cytokines secretion in the splenocytes of immunized mice compared to inactivated EV71 or inactivated CA16. Neonatal mice born to dams immunized with the chimeric VLPs or neonatal mice passively transferred with sera of immunized mice were completely protected from lethal EV71 challenge and partially protected from lethal CA16 infection. Our study provides a novel bivalent or multivalent vaccine strategy to prevent EV71 and related-enterovirus infections.