2017-2021年中国肠道病毒71型灭活疫苗接种现状分析

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。     

WHO working group meeting to develop WHO Recommendations to assure the quality,safety and efficacy of enterovirus 71 vaccines

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.     

A combination vaccine comprising of inactivated enterovirus 71 and coxsackievirus A16 elicits balanced protective immunity against both viruses

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.     

Willingness and influential factors of parents to vaccinate their children with novel inactivated enterovirus 71 vaccines in Guangzhou,China

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.     

某区5岁及以下儿童家长手足口病认知和EV71疫苗接种意愿调查

目的 了解某区5岁及以下儿童家长对手足口病的认知情况和EV71疫苗接种意愿,为制定EV71疫苗免疫策略和健康促进提供科学依据。方法 采用整群随机抽样从北京市某区44家社区卫生服务中心抽取6家,对6家社区卫生服务中心接种门诊接种日当天带领儿童来进行预防接种的5岁及以下儿童家长进行面访并填写调查问卷。结果 该区5岁及以下儿童家长对手足口病防治知识知晓率为71%(95%CI=66%~76%),对预防措施的认知好于对传播途径的认知。儿童母亲(OR=2.77,95%CI=1.67~4.57)、本科/大专以上学历的儿童家长(OR=2.10,95% CI =1.24~3.56)、高年龄儿童的家长(OR=1.58,95%CI=1.10~2.26)知晓率更高。75%的被调查儿童家长表示会为孩子接种EV71疫苗,其中58%的家长更希望能够以“一类疫苗”和28%认为“一类疫苗或二类疫苗都行”的形式提供接种服务;知道我国正在研制EV71疫苗的家长接种意愿高于不知道者(OR=2.57,95%CI=1.17~5.65);25%的被调查儿童家长不会给孩子接种EV71疫苗,“担心疫苗不安全”(67%)和“担心疫苗效果不好”(34%)是最主要原因。结论 对低年龄儿童的家长、低学历家长更应加强手足口病知识宣传,以提高手足口病知识知晓程度。建议优先考虑将EV71疫苗作为一类疫苗进行接种,并通过多种途径向公众报告疫苗研究进展和EV71疫苗宣传,尤其提供预防接种服务的医务人员应积极向儿童家长宣传接种EV71疫苗,以提高儿童家长接种意愿。     

Prospect and challenges for the development of multivalent vaccines against hand,foot and mouth diseases

Enterovirus 71 (EV71), an emerging neurotropic virus and coxsackieviruses (CV) are the major causative agents of hand, foot and mouth diseases (HFMD). These viruses have become a serious public health threat in the Asia Pacific region. Formalin-inactivated EV71 (FI-EV71) vaccines have been developed, evaluated in human clinical trials and were found to elicit full protection against EV71. Their failure to prevent CVA16 infections could compromise the acceptability of monovalent EV71 vaccines. Bivalent FI-EV71/FI-CVA16 vaccines have been found to elicit strong neutralizing antibody responses against both viruses in animal models but did not protect against CVA6 and CVA10 viral infections in cell culture neutralization assay. In this review, we discuss the critical bottlenecks in the development of multivalent HFMD vaccines, including the selection of vaccine strains, animal models to assess vaccine potency, the definition of end-points for efficacy trials, and the need for improved manufacturing processes to produce affordable vaccines.     

A novel inactivated enterovirus 71 vaccine can elicit cross-protective immunity against coxsackievirus A16 in mice

Hand, foot, and mouth disease (HFMD) is a highly contagious disease that mainly affects infants and children. Enterovirus 71 (EV71) and coxsackievirus A16 (CA16) are the major pathogens of HFMD. Two EV71 vaccines were recently licensed in China and the administration of the EV71 vaccines is believed to significantly reduce the number of HFMD-related severe or fatal cases. However, a monovalent EV71 vaccine cannot cross-protect against CA16 infection, this may result in that it cannot effectively control the overall HFMD epidemic. In this study, a chimeric EV71, whose VP1/210–225 epitope was replaced by that of CA16, was constructed using a reverse genetics technique to produce a candidate EV71/CA16 bivalent vaccine strain. The chimeric EV71 was infectious and showed similar growth characteristics as its parental strain. The replacement of the VP1/210–225 epitope did not significantly affect the antigenicity and immunogenicity of EV71. More importantly, the chimeric EV71 could induce protective immunity against both EV71 and CA16, and protect neonatal mice against either EV71 or CA16 lethal infections, the chimeric EV71 constructed in this study was shown to be a feasible and promising candidate bivalent vaccine against both EV71 and CA16. The construction of a chimeric enterovirus also provides an alternative platform for broad-spectrum HFMD vaccines development.     

Establishing China's national standards of antigen content and neutralizing antibody responses for evaluation of enterovirus 71 (EV71) vaccines

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.     

深圳市某区EV71疫苗接种情况与手足口病发病率分析

目的 分析深圳市某区EV71疫苗接种和手足口病(Hand, foot and mouth disease,HFMD)发病的情况,为该区EV71疫苗接种及更好地防控手足口病提供参考依据。 方法 对该区2014—2017年手足口病发病特征及2016年9月—2018年8月EV71疫苗接种情况进行描述性分析。 结果 该区2014—2017年手足口病累计报告发病数61 619例,报告发病数呈逐年下降趋势;布吉和龙岗街道手足口病累计发病28 857例,占全区病例数的46.83%;2016年9月—2018年8月该区累积报告接种EV71疫苗211 865人次,接种第1剂次121 795人次,接种第2剂次90 056人次。 结论 深圳市某区手足口病发病有明显的季节、区域和人群特点,应加强在易感季节对易感人群的宣教和防护工作;加强对EV71疫苗的宣传,提高其接种率。     

Intradermal injection of a fractional dose of an inactivated HFMD vaccine elicits similar protective immunity to intramuscular inoculation of a full dose of an Al(OH)3-adjuvanted vaccine

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.     

High-yield production of recombinant virus-like particles of enterovirus 71 in Pichia pastoris and their protective efficacy against oral viral challenge in mice

Enterovirus 71 (EV71) is one of the major causative pathogens of hand, foot and mouth disease (HFMD), which is highly prevalent in the Asia-Pacific regions. Severe HFMD cases with neurological complications and even death are often associated with EV71 infections. However, no licensed EV71 vaccine is currently available. Recombinant virus-like particles (VLPs) of EV71 have been produced and shown to be a promising vaccine candidate in preclinical studies. However, the performance of current recombinant expression systems for EV71 VLP production remains unsatisfactory with regard to VLP yield and manufacturing procedure, and thus hinders further product development. In this study, we evaluated the expression of EV71 VLPs in Pichia pastoris and determined their protective efficacy in mouse models of EV71 infections. We showed that EV71 VLPs could be produced at high levels up to 4.9% of total soluble protein in transgenic P. pastoris yeast co-expressing P1 and 3CD proteins of EV71. The resulting yeast-produced VLPs potently induced neutralizing antibodies against homologous and heterologous EV71 strains in mice. More importantly, maternal immunization with VLPs protected neonatal mice in both intraperitoneal and oral challenge experiments. Collectively, these results demonstrated the success of simple, high-yield production of EV71 VLPs in transgenic P. pastoris, thus lifting the major roadblock in commercial development of VLP-based EV71 vaccines.     

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.     

EV71: An emerging infectious disease vaccine target in the Far East?

Hand, foot, and mouth disease (HFMD) is a common viral illness in infants and children caused by viruses that belong to the enterovirus genus of the picornavirus family. Although most HFMD do not result in serious complications, outbreaks of HFMD caused by enterovirus 71 (EV71) can present with a high rate of neurological complications, including meningoencephalitis, pulmonary complications, and possibly death. HFMD caused by EV71 has become a major emerging infectious disease in Asia and the highly pathogenic potential of EV71 clearly requires the attention of world medical community. Although vaccine development for EV71 is active and ongoing in Asian countries, a greater joint effort is needed for vaccine researchers and developers in both developed and developing countries to produce a safe and effective EV71 vaccine.     

EV71型病毒疫苗接种后住院患儿手足口病流行病学特征及病原学变化

 目的 了解 EV71型病毒疫苗接种对手足口病流行病学及病原学的影响,为手足口病的防治工作提供科学依据。方法 收集2014—2018年某院手足口病住院患儿病例资料,应用SPSS 18.0软件对数据进行统计,比较EV71型病毒疫苗接种前后(2014年—2016年10月 VS 2016年11月—2018年)住院患儿手足口病的流行病学特征及病原学变化。结果 共收治手足口病住院患儿7 099例,其中普通型6 339例,重症1 570例。与 EV71型病毒疫苗接种前比较,接种后手足口病住院患儿数减少,重症病例所占比率下降,差异有统计学意义(χ²=56.27,P<0.001)。男童患病率高于女童,发病年龄仍然以5岁以下婴幼儿为主,但每个年龄段重症病例均有下降;全年发病呈现两个高峰,分别在5—7月、9—11月;普通型病例以非EV71/CoxA16肠道病毒感染为主,重症病例仍以EV71型病毒感染为主。结论 EV71型病毒疫苗接种后手足口病优势病原体较前发生了明显变化,且重症病例所占比率明显下降,EV71型病毒疫苗值得推广应用。需进一步开展非EV71/CoxA16肠道病毒的分型检测,为手足口病的防治提供更加有力的依据。     

基于真实世界数据研究肠道病毒A71型疫苗对手足口病发病影响的研究进展

手足口病(HFMD)是一种由多种肠道病毒感染所致, 在≤5岁儿童中广泛传播的传染病。目前我国HFMD的流行形势严峻, 发病率较高并持续上升, 造成巨大的疾病负担。肠道病毒A71型(EV-A71)是导致HFMD重症和死亡的原因, EV-A71单价疫苗于2016年上市, 尽管多项临床试验已证明EV-A71疫苗在受试对象中的有效性, 但这并不能反映在真实世界中对一般接种人群的影响。本研究进行系统地文献检索, 对评估EV-A71疫苗在真实应用中对HFMD发病影响的相关研究进行全面回顾与总结, 梳理EV-A71疫苗对HFMD发病影响的真实世界研究的相关证据。目前基于真实世界数据评估EV-A71疫苗对HFMD影响的研究较少, 并且尚无研究对影响HFMD发病的除免疫接种外的其他重要因素(如温度、相对湿度、人口年龄结构、国内生产总值等)进行综合全面考虑。本研究回顾EV-A71疫苗对HFMD影响的真实世界研究有助于清晰和全面了解研究现状, 为今后评估EV-A71疫苗及其他疫苗的短期效果、长期影响等相关研究提供指导和参考。     

Preclinical evaluation of recombinant HFMD vaccine based on enterovirus 71 (EV71) virus-like particles (VLP): Immunogenicity,efficacy and toxicology

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.     

成都市肠道病毒71型灭活疫苗上市后安全性监测分析

目的 分析自2016年肠道病毒71型灭活疫苗( EV71疫苗)上市后,成都市疫苗相关疑似预防接种异常反应(Adverse Events Following Immunization,AEFI) 的发生情况,评价EV71疫苗接种的安全性。方法 通过儿童预防接种信息管理系统（Children Immunization Information Management System,CIIMS）收集2016 - 2017年成都市EV71疫苗接种数据,通过中国AEFI信息管理系统收集同期EV71疫苗相关的AEFI个案数据,采用描述流行病学方法进行分析。结果 截至2017年底,成都市共接种EV71疫苗275 067剂次,共报告EV71疫苗相关AEFI 133例,AEFI总报告发生率为48.35/10万剂,一般反应、异常反应、严重AEFI报告发生率分别为38.54/10万剂、5.09/10万剂、0.73/10万剂。无群体性AEFI,无死亡和残疾的病例,无疫苗质量事故报告。一般反应主要表现为发热（90.57%）,异常反应主要为过敏性皮疹（92.86%）;2例严重AEFI临床诊断为热性惊厥,分类为1例异常反应及1例偶合症。所有AEFI个案转归均为痊愈。结论 成都市接种的EV71疫苗相关AEFI报告发生率及不良反应报告发生率低于全市总体水平,EV71疫苗具有良好的安全性。     

浙江省嘉善县儿童监护人肠道病毒71型疫苗接种意愿及影响因素的调查分析

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.     

北京市2010年手足口病死亡危险因素分析

目的探讨北京市手足口病死亡的危险因素,为防制手足口病、减少手足口病死亡提供科学依据。方法收集2010年北京市手足口病重症和死亡病例资料,采用多因素Logistic回归分析对手足口病死亡的危险因素进行分析。结果 2010年北京市报告重症手足口病610例,其中死亡病例18例,重症病例病死率为2.95%。结果显示:患者年龄、户口类型为流动人口、诊断重症病例的医院类型为县医院、到村级(个体)医疗机构就诊和病原检测结果为肠道病毒71型(enterovirus 71,EV71)是重症手足口病死亡的影响因素。结论为减少手足口病死亡病例的发生,应重视1岁以下婴幼儿,流动人口和EV71感染儿童的防控工作,手足口病患者应到正规医院就诊,发现重症早期症状者应立即转诊到具有诊治重症病例能力的医疗机构进行科学规范救治。     

Hexon-modified recombinant E1-deleted adenoviral vectors as bivalent vaccine carriers for Coxsackievirus A16 and Enterovirus 71

Hand, foot and mouth disease (HFMD) is a major public health concern in Asia; more efficient vaccines against HFMD are urgently required. Adenoviral (Ad) capsids have been used widely for the presentation of foreign antigens to induce specific immune responses in the host. Here, we describe a novel bivalent vaccine for HFMD based on the hexon-modified, E1-deleted chimpanzee adenovirus serotype 68 (AdC68). The novel vaccine candidate was generated by incorporating the neutralising epitope of Coxsackievirus A16 (CA16), PEP71, into hypervariable region 1 (HVR1), and a shortened neutralising epitope of Enterovirus 71 (EV71), sSP70, into HVR2 of the AdC68 hexon. In order to enhance the immunogenicity of EV71, VP1 of EV71 was cloned into the E1-region of the AdC68 vectors. The results demonstrated that these two epitopes were well presented on the virion surface and had high affinity towards specific antibodies, and VP1 of EV71 was also significantly expressed. In pre-clinical mouse models, the hexon-modified AdC68 elicited neutralising antibodies against both CA16 and EV71, which conferred protection to suckling mice against a lethal challenge of CA16 and EV71. In summary, this study demonstrates that the hexon-modified AdC68 may represent a promising bivalent vaccine carrier against EV71 and CA16 and an epitope-display platform for other pathogens.