Immunogenicity and safety of an inactivated #EV71 #vaccine administered simultaneously with recombinant #hepatitis B vaccine and group A #meningococcal polysaccharide vaccine… (J Infect Dis., abstract)

[Source: Journal of Infectious Diseases, full page: (LINK). Abstract, edited.]

Immunogenicity and safety of an inactivated enterovirus 71 vaccine administered simultaneously with recombinant hepatitis B vaccine and group A meningococcal polysaccharide vaccine:  a phase IV, open-label, single-center, randomized, non-inferiority trial

Zewu Zhang, MS, Zhenglun Liang, PhD, Ji Zeng, MS, Jikai Zhang, MS, Peng He, MS, Jiali Su, MS, Yaoming Zeng, BS, Renfeng Fan, MS, Dan Zhao, BS, Wenjun Ma, MS, Gang Zeng, PhD, Qiaoli Zhang, MS, Huizhen Zheng, BS

The Journal of Infectious Diseases, jiz129, https://doi.org/10.1093/infdis/jiz129

Published: 19 March 2019

 

Abstract

Background

This study tested the hypothesis that the immunogenicity and safety of the simultaneous administration of the combined EV71 vaccine with recombinant hepatitis B vaccine (HepB) and group A meningococcal polysaccharide vaccine (MenA) is not inferior to separate administration of each vaccine.

Methods

The study was designed as a randomized, open-label, and non-inferiority trial, and was registered at ClinicalTrials.gov (NCT03274102). A total of 775 healthy infants aged 6 months were randomized 1:1:1 to simultaneous administration (SI) or separate administration (SE1:EV71 and SE2: HepB followed by MenA).

Results

According to per protocol set, antibody response against EV71, hepatitis B virus and group A meningococcal polysaccharide was similar regardless of administration schedule. With the non-inferiority margin set at 10%, the seroconversion of the three pathogens in the SI group (100% [98.25, 100], 44.84% [38.20, 51.63] and 27.83% [21.91, 34.38]) was not inferior to that of SE1 or SE2 group (100% [98.31, 100], 44.35% [37.82, 51.02] and 29.17% [23.20, 35.72]). The occurrences of adverse reactions of each vaccination regimen were comparable (60.62% vs 52.33% and 56.98%, P = 0.16).

Conclusions

Simultaneous administration of combined EV71 vaccine with HepB and MenA shows non inferiority in immunogenicity and safety compared with separate administration.

Clinical Trial Registration NCT03274102

simultaneous administration, EV71 vaccine, phase-IV trial

Issue Section: Major Article

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© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Keywords: Enterovirus; EV-71; Vaccines.

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Hsp27 responds to and facilitates #enterovirus A71 #replication through enhancing viral IRES-mediated translation (J Virol., abstract)

[Source: Journal of Virology, full page: (LINK). Abstract, edited.]

Hsp27 responds to and facilitates enterovirus A71 replication through enhancing viral IRES-mediated translation

Xuelian Dan, Qianya Wan, Lina Yi, Jing Lu, Yang Jiao, Huangcan Li, Dan Song, Ying Chen, Hongxi Xu, Ming-Liang He

DOI: 10.1128/JVI.02322-18

 

ABSTRACT

Enterovirus 71 (EV-A71) is a human pathogen that causes hand, foot and mouth disease (HFMD) and fatal neurological diseases without effective treatment. Characterization of key host factors is important for understanding pathogenesis and developing antiviral drugs. Revealed by two-dimensional gel electrophoresis-based proteomics studies, here we report that Hsp27 is one of the most upregulated proteins responding to EV-A71 infection. Depletion of Hsp27 by siRNA or CRISPR-Cas9 mediated knockout significantly inhibits viral replication, protein expression and reproduction; while restoration of Hsp27 rescores such virus activities. Furthermore, we show that Hsp27 plays crucial role in regulating the viral internal ribosome entry site (IRES) activities by two different mechanisms. Hsp27 markedly promotes 2Apro-mediated eIF4G cleavage, an important process for selecting and initiating IRES-mediated translation. hnRNP A1 is a key IRES trans-acting factor (ITAF) for enhancing IRES-mediated translation. Surprisingly, knockout of Hsp27 differentially blocks hnRNP A1 but not FBP1 translocation from nucleus to cytoplasm, and therefore abolishes hnRNP A1 interaction with IRES. Most importantly, Hsp27 inhibitor TDP, a compound was isolated from a traditional Chinese herb, significantly protects cytopathic effects and inhibits EV-A71 infection. Collectively, our results demonstrate new functions of Hsp27 in facilitating virus infection and provides novel options for combating EV-A71 infection by targeting Hsp27.

 

IMPORTANCE

EV-A71 outbreak, repeatedly reported worldwide in the last decades, is a great public health problem for causing hand, foot and mouth disease and severe neurological disorders even deaths without approved treatments available. We show Hsp27, a heat shock protein, supports EV-A71 infection through two distinct ways to promote viral IRES dependent translation. A small molecule Hsp27 inhibitor isolated from traditional Chinese medical herb effectively reduced the virus yields. Together, we demonstrate that Hsp27 plays important role in EV-A71 infection and may serve as antiviral target.

Copyright © 2019 American Society for Microbiology. All Rights Reserved.

Keywords: EV-A71; Enterovirus; Antivirals.

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High permissiveness for #genetic exchanges between #enteroviruses of species A, including enterovirus 71, favours #evolution through intertypic #recombination in #Madagascar (J Virol., abstract)

[Source: Journal of Virology, full page: (LINK). Abstract, edited.]

High permissiveness for genetic exchanges between enteroviruses of species A, including enterovirus 71, favours evolution through intertypic recombination in Madagascar

Romain Volle, Richter Razafindratsimandresy, Marie-Line Joffret, Maël Bessaud, Sendraharimanana Rabemanantsoa, Seta Andriamamonjy, Jonhson Raharinantoanina, Bruno Blondel,Jean-Michel Heraud, Jean-Luc Bailly, Francis Delpeyroux

DOI: 10.1128/JVI.01667-18

 

ABSTRACT

Human enteroviruses of species A (EV-A) are the leading cause of hand-foot-and-mouth disease (HFMD). EV-A71 is frequently implicated in HFMD outbreaks and can also cause severe neurological manifestations. We investigated the molecular epidemiological processes at work and the contribution of genetic recombination to the evolutionary history of EV-A in Madagascar, focusing on the recently described EV-A71 genogroup F in particular. Twenty-three EV-A isolates, mostly collected in 2011 from healthy children living in various districts of Madagascar, were characterised by whole-genome sequencing. Eight different types were identified, highlighting the local circulation and diversity of EV-A. Comparative genome analysis revealed evidence of frequent recent intra- and intertypic genetic exchanges between the non-capsid sequences of Madagascan EV-A isolates. The three EV-A71 isolates had different evolutionary histories in terms of recombination, with one isolate displaying a mosaic genome resulting from recent genetic exchanges with Madagascan coxsackieviruses A7 and possibly -A5 and -A10 or common ancestors. The engineering and characterisation of recombinants generated from progenitors belonging to different EV-A types or EV-A71 genogroups with distantly related non-structural sequences indicated a high level of permissiveness for intertypic genetic exchange in EV-A. This permissiveness suggests that the primary viral functions associated with the non-structural sequences have been highly conserved, through the diversification and evolution of the EV-A species. No outbreak of disease due to EV-A has yet been reported in Madagascar, but the diversity, circulation and evolution of these viruses justify surveillance of EV-A circulation and HFMD cases, to prevent possible outbreaks due to emerging strains.

 

IMPORTANCE

Human enteroviruses of species A (EV-A), including EV-A71, are the leading cause of hand-foot-and-mouth disease (HFMD), and may also cause severe neurological manifestations. We investigated the circulation and molecular evolution of EV-A in Madagascar, focusing particularly on the recently described EV-A71 genogroup F. Eight different types, mostly collected in 2011, were identified, highlighting the local circulation and diversity of EV-A. Comparative genome analysis revealed evidence of frequent genetic exchanges between the different types of isolates. The three EV-A71 isolates had different evolutionary histories in terms of recombination. The engineering and characterisation of recombinants involving progenitors belonging to different EV-A types indicated a high degree of permissiveness for genetic exchange in EV-A. No outbreak of disease due to EV-A has yet been reported in Madagascar, but the diversity, circulation and evolution of these viruses justify the surveillance of EV-A circulation, to prevent possible HFMD outbreaks due to emerging strains.

Copyright © 2019 American Society for Microbiology. All Rights Reserved.

Keywords: Enterovirus; Recombination; EV-A71; Coxsackievirus A5-A7-A10; HFMD; Madagascar.

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#Enterovirus A71 #Infection and #Neurologic Disease, Madrid, #Spain, 2016 (Emerg Infect Dis., abstract)

[Source: US Centers for Disease Control and Prevention (CDC), Emerging Infectious Diseases Journal, full page: (LINK). Abstract, edited.]

Volume 25, Number 1—January 2019 / CME ACTIVITY – Synopsis

Enterovirus A71 Infection and Neurologic Disease, Madrid, Spain, 2016

Carmen Niño Taravilla1  , Isabel Pérez-Sebastián1, Alberto García Salido, Claudia Varela Serrano, Verónica Cantarín Extremera, Anna Duat Rodríguez, Laura López Marín, Mercedes Alonso Sanz, Olga María Suárez Traba, and Ana Serrano González

Author affiliations: Hospital Infantil Universitario Niño Jesús, Madrid, Spain

 

Abstract

We conducted an observational study from January 2016 through January 2017 of patients admitted to a reference pediatric hospital in Madrid, Spain, for neurologic symptoms and enterovirus infection. Among the 30 patients, the most common signs and symptoms were fever, lethargy, myoclonic jerks, and ataxia. Real-time PCR detected enterovirus in the cerebrospinal fluid of 8 patients, nasopharyngeal aspirate in 17, and anal swab samples of 5. The enterovirus was genotyped for 25 of 30 patients; enterovirus A71 was the most common serotype (21/25) and the only serotype detected in patients with brainstem encephalitis or encephalomyelitis. Treatment was intravenous immunoglobulins for 21 patients and corticosteroids for 17. Admission to the pediatric intensive care unit was required for 14 patients. All patients survived. At admission, among patients with the most severe disease, leukocytes were elevated. For children with brainstem encephalitis or encephalomyelitis, clinicians should look for enterovirus and not limit testing to cerebrospinal fluid.

Keywords: EV-A71; Encephalitis; Spain.

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#Surveillance of #enteroviruses from #paediatric patients attended at a tertiary #hospital in #Catalonia from 2014 to 2017 (J Clin Virol., abstract)

[Source: Science Direct, full page: (LINK). Abstract, edited.]

Journal of Clinical Virology / Available online 30 November 2018 / In Press, Accepted Manuscript

Surveillance of enteroviruses from paediatric patients attended at a tertiary hospital in Catalonia from 2014 to 2017

Cristina Andrés a, Jorgina Vila b, Laura Gimferrer a , Maria Piñana a, Juliana Esperalba a, Maria Gema Codina a, Meritxell Barnés b, Mariadel Carmen Martín a, Francisco Fuentes a, Susana Rubio a, Pilar Alcubilla a, Carlos Rodrigo b, Tomàs Pumarola a, Andrés Antón a

{a} Respiratory Viruses Unit, Virology Section, Microbiology Department, Hospital Universitari Vall d’Hebron, Vall d’Hebron Research Institute, Universitat Autònoma de Barcelona, Barcelona, Spain; {b} Paediatric Hospitalisation Unit, Department of Paediatrics, Hospital Universitari Maternoinfantil Vall d’Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain

Received 4 September 2018, Revised 26 October 2018, Accepted 16 November 2018, Available online 30 November 2018.

DOI: https://doi.org/10.1016/j.jcv.2018.11.004

 

Highlights

  • The study reports virological and clinical enterovirus surveillance in Catalonia.
  • The four enterovirus species cocirculated, distinguishing up to 27 different types.
  • Most of neurological studied cases were from the 2016 spring outbreak.
  • EV-A71 was one of the most detected EV, mostly during the outbreak.
  • Rhombencephalitis cases were related to EV-A71 infection.
  • EV-D68 was associated with lower respiratory tract infections.
  • Necessity to perform EV surveillance in primary care settings.

 

Abstract

Background

Enterovirus (EV) infections are usually asymptomatic or mild, but symptomatic infections can evolve to severe complications. Outbreaks of EV-A71 and EV-D68 have been recently reported worldwide, sometimes related to severe clinical outcomes.

Objective

To describe EV genetic diversity and the clinical outcomes from paediatric patients attended at a tertiary university hospital in Barcelona (Catalonia, Spain) from 2014 to 2017.

Study design

Specimens were collected from paediatric (<17 years old) cases with suspicion of respiratory tract infection or EV infection. EV laboratory-confirmation was performed by specific real-time multiplex RT-PCR assay. Partial viral VP1 protein was sequenced for genetic characterisation by phylogenetic analyses.

Results

A total of 376 (7%) from 5,703 cases were EV laboratory-confirmed. Phylogenetic analyses of VP1 (210; 81%) sequences distinguished up to 27 different EV types distributed within EV-A (82; 40%), EV-B (90; 42%), EV-C (5; 2%), and EV-D (33; 15%), in addition to 50 (19%) rhinoviruses. The most predominant were EV-A71 (37; 45%) and EV-D68 (32; 99%). EV-A71 was highly related to neurological complications (25/39, 63%), of which 20/39 were rhombencephalitis, and most EV-D68 (28/32, 88%) were associated with lower respiratory tract infections (LRTI), and exceptionally one (3%) with flaccid paralysis.

Conclusions

EV-A71 and EV-D68 were the most detected EV in respiratory specimens. EV-A71 was highly related to neurological disease and EV-D68 was often associated with LRTI. However, both potential relatedness to neurological diseases makes the monitoring of EV circulation obligatory.

Keywords: enteroviruses – respiratory infections – surveillance – genetic diversity – molecular epidemiology – paediatric population

© 2018 Elsevier B.V. All rights reserved.

Keywords: Enterovirus; EV-A71; EV-D68; Rhomboencephalitis; AFP; Spain.

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IL-10-592 #Polymorphism is Associated with IL-10 Expression and #Severity of #Enterovirus 71 #Infection in #Chinese #Children (J Clin Virol., abstract)

[Source: Journal of Clinical Virology, full page: (LINK). Abstract, edited.]

IL-10-592 Polymorphism is Associated with IL-10 Expression and Severity of Enterovirus 71 Infection in Chinese Children

Na Zhao, Hui-lan Chen, Zhen-zhen Chen, Jing Li, Zong-bo Chen

DOI: http://dx.doi.org/10.1016/j.jcv.2017.08.005

Publication History: Published online: August 18, 2017 – Accepted: August 10, 2017 – Received in revised form: July 18, 2017 – Received: April 11, 2017

 

Highlights

  • IL-10-592 C allele is related to critical EV71 infection.
  • IL-10-592 A/A could decrease IL-10 level.
  • IL-10 in plasma was elevated in critical EV71 infection cases.

 

Abstract

Background

Enterovirus 71 (EV71) infection results in some severe complications with high mortality and disability in Hand, Foot and Mouth Disease (HFMD) in children. Recent studies have shown that cytokine genetic predispositions have associations with both the development of EV71 infection and severity of HFMD.

Objective

This study was designed to investigate whether the IL-10–592 polymorphism is associated with IL-10 levels and disease severity in Chinese children with EV71 infection.

Study design

In patients selected, there were 378 cases with EV71 infection (including 291 mild cases, 70 severe cases and 17 critical cases), as well as 406 health controls. EV71 in serum was tested by RT-PCR, and IL-10-592 genotype was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis techniques.

Result

The IL-10-592C allele was observed with higher frequency in patients with critical EV71 infection (70.59%) compared with severe EV71 infection (41.43%, P < 0.01), mild EV71 infection (43.81%, P < 0.01) and healthy children (44.46%, P < 0.01). The blood IL-10 levels of critical cases were significantly higher than severe cases, mild cases, and healthy children. Among all of the four groups, IL-10 levels in patients with genotype AA were significantly lower than those with genotypes AC + CC (t = 4.86, P < 0.05; t = 2.30, P < 0.05; t = 3.44, P < 0.05; t = 5.58, P < 0.05).

Conclusion

IL-10-592C allele is associated with IL-10 expressions and the severity of EV71 infection in Chinese patients.

Keywords: Enterovirus 71 infection, IL-10, Gene polymorphism

Keywords: EV-71; Enterovirus; HFMD; China; Genetics.

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An inactivated #HFMD #vaccine using the #EV71 (C4a) strain isolated from a #Korean patient induces a strong immunogenic response in mice (PLoS One, abstract)

[Source: PLoS One, full page: (LINK). Abstract, edited.]

OPEN ACCESS / PEER-REVIEWED / RESEARCH ARTICLE

An inactivated hand-foot-and-mouth disease vaccine using the enterovirus 71 (C4a) strain isolated from a Korean patient induces a strong immunogenic response in mice

Hyun Ju In , Heeji Lim , Jung-Ah Lee, Hye Jin Kim, Jin-Won Kim, Ji-Yeon Hyeon, Sang-Gu Yeo, June-Woo Lee, Jung Sik Yoo, Young Ki Choi, Sang-Won Lee

Published: May 24, 2017 / https://doi.org/10.1371/journal.pone.0178259

 

Abstract

Enterovirus 71 (EV71) is a major causative agent of hand-foot-and-mouth disease (HFMD) frequently occurring in children. HFMD induced by EV71 can cause serious health problems and has been reported worldwide, particularly in the Asia-Pacific region. In this study, we assessed the immunogenicity of a formalin-inactivated HFMD vaccine using an EV71 strain (FI-EV71 C4a) isolated from a Korean patient. The vaccine candidate was evaluated in mice to determine the vaccination doses and vaccine schedules. BALB/c mice were intramuscularly administered 5, 10, or 20 μg FI-EV71 vaccine, followed by a booster 2 weeks later. EV71-specific antibodies and neutralizing antibodies were induced and maintained until the end of the experimental period in all vaccinated groups. To determine the effectiveness of adjuvant for the EV71 vaccine, three adjuvants, i.e., aluminium hydroxide gel, monophosphoryl lipid A, and polyinosinic-polycytidylic acid, were administered separately with the FI-EV71 vaccine to mice via the intramuscular route. Mice administered the FI-EV71 vaccine formulated with all three adjuvants induced a significantly increased antibody response compared with that of the single adjuvant groups. The vaccinated group with triple adjuvants exhibited more rapid induction of EV71-specific and neutralizing antibodies than the other groups. These results suggested that the role of adjuvant in inactivated vaccine was important for eliciting effective immune responses against EV71. In conclusion, our results showed that FI-EV71 was a potential candidate vaccine for prevention of EV71 infection.

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Citation: In HJ, Lim H, Lee J-A, Kim HJ, Kim J-W, Hyeon J-Y, et al. (2017) An inactivated hand-foot-and-mouth disease vaccine using the enterovirus 71 (C4a) strain isolated from a Korean patient induces a strong immunogenic response in mice. PLoS ONE 12(5): e0178259. https://doi.org/10.1371/journal.pone.0178259

Editor: Ralph Tripp, University of Georgia, UNITED STATES

Received: February 7, 2017; Accepted: April 26, 2017; Published: May 24, 2017

Copyright: © 2017 In et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are included within the paper and its Supporting Information files.

Funding: This work was supported by grants from the Korea National Institute of Health (grant no. NIH 4800-4845-300). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

Keywords: Enterovirus 71; HFMD; Vaccines.

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