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EV71 vaccine

Kan Xing Wu, Patchara Phuektes, Pankaj Kumar, Germaine Yen Lin Goh, Dimitri Moreau, Vincent Tak Kwong Chow, Frederic Bard, Justin Jang Hann Chu
Enterovirus 71 (EV71) is a neurotropic enterovirus without antivirals or vaccine, and its host-pathogen interactions remain poorly understood. Here we use a human genome-wide RNAi screen to identify 256 host factors involved in EV71 replication in human rhabdomyosarcoma cells. Enrichment analyses reveal overrepresentation in processes like mitotic cell cycle and transcriptional regulation. We have carried out orthogonal experiments to characterize the roles of selected factors involved in cell cycle regulation and endoplasmatic reticulum-associated degradation...
October 17, 2016: Nature Communications
Yong Wah Tan, Melgious Jin Yan Ang, Qiu Ying Lau, Anders Poulsen, Fui Mee Ng, Siew Wen Then, Jianhe Peng, Jeffrey Hill, Wan Jin Hong, Cheng San Brian Chia, Justin Jang Hann Chu
Hand, Foot and Mouth Disease is a highly contagious disease caused by a range of human enteroviruses. Outbreaks occur regularly, especially in the Asia-Pacific region, putting a burden on public healthcare systems. Currently, there is no antiviral for treating this infectious disease and the only vaccines are limited to circulation in China, presenting an unmet medical need that needs to be filled urgently. The human enterovirus 3 C protease has been deemed a plausible drug target due to its essential roles in viral replication...
2016: Scientific Reports
Jialei Sun, Jane Ennis, Jeffrey D Turner, Justin Jang Hann Chu
Enterovirus 71 (EV71) causes hand-foot-and-mouth diseases as well as neurological complications in young children. Interferon (IFN) can inhibit the replication of many viruses with low cytotoxic effects. Previously, an adenovirus vectored mouse interferon-α (DEF201), subtype 5, was generated by Wu et al, 2007. In this study, the antiviral effects of DEF201 against EV71 were evaluated in a murine model. 6-day-old BALB/c mice were administered a single dose of DEF201 before or after infection with lethal dose of EV71...
October 2016: Antiviral Research
Ping-Chin Chang, Shou-Chien Chen, Kow-Tong Chen
Enterovirus 71 (EV71) infections have a major public health impact in the Asia-Pacific region. We reviewed the epidemiology, pathogenesis, and molecular epidemiology of EV71 infection as well as EV71 vaccine development. Previous studies were found using the search terms "enterovirus 71" and "epidemiology" or "pathogenesis" or "molecular epidemiology" or "vaccine" in Medline and PubMed. Articles that were not published in the English language, manuscripts without an abstract, and opinion articles were excluded from the review...
2016: International Journal of Environmental Research and Public Health
Juan Xu, Chunhua Zhang
Enterovirus (EV71) can cause severe neurological diseases, but the underlying pathogenesis remains unclear. The capsid protein, viral protein 1 (VP1), plays a critical role in the pathogenicity of EV71. High level expression and secretion of VP1 protein are necessary for structure, function and immunogenicity in its natural conformation. In our previous studies, 5 codon-optimized VP1 DNA vaccines, including wt-VP1, tPA-VP1, VP1-d, VP1-hFc and VP1-mFc, were constructed and analyzed. They expressed VP1 protein, but the levels of secretion and immunogenicity of these VP1 constructs were significantly different (P<0...
May 2016: Journal of Biomedical Research
Elizabeth A Caine, Louise H Moncla, Monica D Ronderos, Thomas C Friedrich, Jorge E Osorio
UNLABELLED: Hand, foot, and mouth disease (HFMD) has spread throughout the Asia-Pacific region, affecting millions of young children, who develop symptoms ranging from painful blisters around their mouths and hands to neurological complications. Many members of the genus Enterovirus (family Picornaviridae) cause HFMD. Enterovirus 71 (EV71) is one of the primary causative agents and has been linked to severe disease. Vaccine efficacy and pathogenesis studies for EV71 have been limited because there is a lack of suitable animal models...
October 1, 2016: Journal of Virology
Qin Yan, Linjuan Wu, Longyun Chen, Yali Qin, Zishu Pan, Mingzhou Chen
Enterovirus 71 (EV71) belonging to the Picornaviridae family is considered the most frequently detected causative agent in hand-foot-and-mouth disease (HFMD) and is a serious threat to public health in the Asia-Pacific region. There are currently no approved vaccines or effective drugs for EV71. In this study, using recombinant vesicular stomatitis virus (rVSV) expressing viral VP1 protein (mVP1) of EV71 as a control, we generated two types of rVSVs that can form EV71 virus-like particles (VLPs). First, we co-infected two rVSVs singly expressing P1 (mP1) and 3CD (m3CD) of EV71...
July 29, 2016: Vaccine
Lei Yin Emily Ang, Horng Khit Issac Too, Eng Lee Tan, Tak-Kwong Vincent Chow, Pei-Chi Lynette Shek, Elizabeth Tham, Sylvie Alonso
BACKGROUND: Recurrence of hand, foot and mouth disease (HFMD) pandemics continues to threaten public health. Despite increasing awareness and efforts, effective vaccine and drug treatment have yet to be available. Probiotics have gained recognition in the field of healthcare worldwide, and have been extensively prescribed to babies and young children to relieve gastrointestinal (GI) disturbances and diseases, associated or not with microbial infections. Since the faecal-oral axis represents the major route of HFMD transmission, transient persistence of probiotic bacteria in the GI tract may confer some protection against HFMD and limit transmission among children...
2016: Virology Journal
Wee Ming Koh, Tiffany Bogich, Karen Siegel, Jing Jin, Elizabeth Y Chong, Chong Yew Tan, Mark Ic Chen, Peter Horby, Alex R Cook
CONTEXT: Hand, foot and mouth disease (HFMD) is a widespread pediatric disease caused primarily by human enterovirus 71 (EV-A71) and Coxsackievirus A16 (CV-A16). OBJECTIVE: This study reports a systematic review of the epidemiology of HFMD in Asia. DATA SOURCES: PubMed, Web of Science and Google Scholar were searched up to December 2014. STUDY SELECTION: Two reviewers independently assessed studies for epidemiologic and serologic information about prevalence and incidence of HFMD against predetermined inclusion/exclusion criteria...
October 2016: Pediatric Infectious Disease Journal
Yang Zhou, Jing-Xin Li, Peng-Fei Jin, Yu-Xiao Wang, Feng-Cai Zhu
INTRODUCTION: Enterovirus A71 (EV71) is the predominant causative agent of hand, foot, and mouth disease (HFMD), which is often associated with severe cases and even deaths. EV71-associated epidemics have emerged as a serious threat to public health, particularly in the Asia-Pacific region. AREAS COVERED: We searched PubMed using the terms 'enterovirus 71', 'hand, foot, and mouth disease', and 'vaccine', with no date or language restrictions for all publications before April 27, 2016...
July 2016: Expert Review of Vaccines
X Peng, X Fang, J Li, L Kong, B Li, X Ding
Enterovirus 71 (EV71) is a major causative viral agent for large outbreaks of hand, foot, and mouth disease in children and infants, yet there is no vaccine or effective antiviral treatment for severe EV71 infection. The immunogenicity of EV71 VP1 DNA vaccine and the immunoregulatory activity of interleukin-12 (IL-12) or granulocyte-monocyte colony stimulating factor (GM-CSF) were investigated. DNA vaccine plasmids, pcDNA-VP1, pcDNA-IL-12 and pcDNA-GM-CSF were constructed and inoculated into BALB/c mice with or without pcDNA-IL-12 or pcDNA-GM-CSF by intramuscular injection...
2016: Cellular and Molecular Biology
Shubing Tang, Baoqin Xuan, Xiaohua Ye, Zhong Huang, Zhikang Qian
Virus-like particles (VLPs) can be used as powerful nanoscale weapons to fight against virus infection. In addition to direct use as vaccines, VLPs have been extensively exploited as platforms on which to display foreign antigens for prophylactic vaccination and immunotherapeutic treatment. Unfortunately, fabrication of new chimeric VLP vaccines in a versatile, site-specific and highly efficient manner is beyond the capability of traditional VLP vaccine design approaches, genetic insertion and chemical conjugation...
2016: Scientific Reports
Celeste Donato, Le Thi Hoi, Nguyen Thi Hoa, Tran Mai Hoa, Le Van Duyet, Ta Thi Dieu Ngan, Nguyen Van Kinh, Nguyen Vu Trung, Dhanasekaran Vijaykrishna
BACKGROUND: Enterovirus 71 subgenogroup C4 caused the largest outbreak of Hand, Foot and Mouth Disease (HFMD) in Vietnam during 2011-2012, resulting in over 200,000 hospitalisations and 207 fatalities. METHODS: A total of 1917 samples with adequate volume for RT-PCR analysis were collected from patients hospitalised with HFMD throughout Vietnam and 637 were positive for EV71. VP1 gene (n=87) and complete genome (n=9) sequencing was performed. Maximum-likelihood phylogenetic analysis was performed to characterise the B5, C4 and C5 strains detected...
August 2016: Virology
Y Xia, J Shan, H Ji, J Zhang, Hb Yang, Q Shen, Xr Ya, Rf Tian, Cf Wang, C Liu, Cm Ni, H Liu
Hand, foot, and mouth disease (HFMD) is a common childhood illness that is caused by enteroviruses, and the prevalence of HFMD in China and around the world has resulted in a huge disease burden. Since 2010, the HFMD incidence has been the highest among infectious diseases in Suzhou, China. To investigate the epidemical, features, etiological characteristics, and clinical characteristics of HFMD in Suzhou City, East China, from 2011 to 2014. We retrospectively analyzed HFMD epidemiological data in Suzhou from 2011 to 2014...
July 2016: Archives of Virology
Hangyu Zhou, Guangchuan Wang, Xiao-Feng Li, Yaling Li, Shun-Ya Zhu, Cheng-Feng Qin, Ruikang Tang
Developing vaccine formulations with excellent thermostability and immunogenicity remains a great challenge. By in situ encapsulating a live-attenuated strain of human enterovirus 71 (EV71) in alumina, we obtained a robust vaccine formulation named EV71@NanoAlum, which features significantly enhanced thermostability and immunogenicity. This attempt follows a material-based tactic for vaccine improvement.
May 11, 2016: Chemical Communications: Chem Comm
Jie Shao, Fan Gao, Hui-Juan Lin, Qun-Ying Mao, Pan Chen, Xing Wu, Xin Yao, Wei Kong, Zheng-Lun Liang
To reduce potential oncogenic long genomic DNA in vaccines, nuclease treatment has been applied in the purification processes. However, this action increased the residue of short-fragment DNA and its effect on vaccine potency was still elusive. In this study, we found residual sf-DNA in an inactivated EV71 vaccine could enhance humoral immune response in mice. Ag stimulation in vitro and vaccine injection in vivo revealed that TLR9 transcription level was elevated, indicating that sf-DNA could activate TLR9...
2016: PloS One
Kun-Teng Wang, Shih-Jie Lin, Hsiu-Chi Wang, Pin-Chun Chen, Jiao-Jung Lin, Jen-Ron Chiang, Chao-Liang Chang, Daniel Yang-Chih Shih, Chi-Fang Lo, Der-Yuan Wang
Enterovirus 71 (EV71) belongs to the Enterovirus genus of the Picornaviridae family, and its occurrence in Asia is associated with hand-foot-and-mouth disease (HFMD), leading to death in some cases, in young children. An effective EV71 vaccine is therefore urgently needed. In this study, we established a two-step EV71 vaccine potency model. Intraperitoneal injections in 2-day-old suckling mice were used to establish the LD50 of EV71 B4, B5, C2, C4, and C5 subgenotypes. Only C4 caused hind limb paralysis in mice (LD50: 2...
July 2016: Biologicals: Journal of the International Association of Biological Standardization
Ans Timmermans, Melanie C Melendrez, Youry Se, Ilin Chuang, Nou Samon, Nichapat Uthaimongkol, Chonticha Klungthong, Wudtichai Manasatienkij, Butsaya Thaisomboonsuk, Stuart D Tyner, Sareth Rith, Viseth Srey Horm, Richard G Jarman, Delia Bethell, Nitima Chanarat, Julie Pavlin, Tippa Wongstitwilairoong, Piyaporn Saingam, But Sam El, Mark M Fukuda, Sok Touch, Ly Sovann, Stefan Fernandez, Philippe Buchy, Lon Chanthap, David Saunders
Little is known about circulation of influenza and other respiratory viruses in remote populations along the Thai-Cambodia border in western Cambodia. We screened 586 outpatients (median age 5, range 1-77) presenting with influenza-like-illness (ILI) at 4 sentinel sites in western Cambodia between May 2010 and December 2012. Real-time reverse transcriptase (rRT) PCR for influenza was performed on combined nasal and throat specimens followed by viral culture, antigenic analysis, antiviral susceptibility testing and full genome sequencing for phylogenetic analysis...
2016: PloS One
Joseph T Wu, Mark Jit, Yaming Zheng, Kathy Leung, Weijia Xing, Juan Yang, Qiaohong Liao, Benjamin J Cowling, Bingyi Yang, Eric H Y Lau, Saki Takahashi, Jeremy J Farrar, Bryan T Grenfell, Gabriel M Leung, Hongjie Yu
BACKGROUND: China accounted for 87% (9.8 million/11.3 million) of all hand, foot, and mouth disease (HFMD) cases reported to WHO during 2010-2014. Enterovirus 71 (EV71) is responsible for most of the severe HFMD cases. Three EV71 vaccines recently demonstrated good efficacy in children aged 6-71 mo. Here we assessed the cost-effectiveness of routine pediatric EV71 vaccination in China. METHODS AND FINDINGS: We characterized the economic and health burden of EV71-associated HFMD (EV71-HFMD) in China using (i) the national surveillance database, (ii) virological surveillance records from all provinces, and (iii) a caregiver survey on the household costs and health utility loss for 1,787 laboratory-confirmed pediatric cases...
March 2016: PLoS Medicine
Zarifah Reed, Mary Jane Cardosa
Although outbreaks of Hand, Foot, and Mouth Disease (HFMD) in young children have long been recognized worldwide, the occurrence of rare and life-threatening neurological, respiratory, and cardiac complications has propelled this common condition into the spotlight as a major public health problem in the affected countries. Various enteroviruses cause HFMD, but the severe complications have been mostly associated with enterovirus 71 (EV71). Medical treatment is supportive and measures to interrupt transmission have been challenging to implement...
June 3, 2016: Vaccine
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