Inactivated enterovirus A71 vaccines and moving forward

Enteroviruses are associated with various diseases accompanied by rare but severe complications. In recent years, outbreaks of enterovirus D68 and enterovirus A71 associated with severe respiratory infections and neurological complications have been reported worldwide. Since information on molecular epidemiology in respiratory samples is still limited, the genetic diversity of enteroviruses was retrospectively analysed over a 4-year period (2013–2016) in respiratory samples from paediatric patients. Partial viral major capsid protein gene (VP1) sequences were determined for genotyping. Enteroviruses were detected in 255 (6.1%) of 4187 specimens. Phylogenetic analyses of 233 (91.4%) strains revealed 25 different genotypes distributed to Enterovirus A (39.1%), Enterovirus B (34.3%), and Enterovirus D (26.6%). The most frequently detected genotypes were enterovirus D68 (26.6%), coxsackievirus A6 (15.9%), and enterovirus A71 (7.3%). Enterovirus D68 detections were associated with lower respiratory tract infections and increased oxygen demand. Meningitis/encephalitis and other neurological symptoms were related to enterovirus A71, while coxsackievirus A6 was associated with upper respiratory diseases. Prematurity turned out as a potential risk factor for increased oxygen demand during enterovirus infections. The detailed analysis of epidemiological and clinical data contributes to the non-polio enterovirus surveillance in Europe and showed high and rapidly changing genetic diversity of circulating enteroviruses, including different enterovirus D68 variants.

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Bioinformatics-based prediction of conformational epitopes for Enterovirus A71 and Coxsackievirus A16

Scientific Reports ◽

10.1038/s41598-021-84891-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Liping Wang ◽

Miao Zhu ◽

Yulu Fang ◽

Hao Rong ◽

Liuying Gao ◽

...

Keyword(s):

Foot And Mouth Disease ◽

Distribution Patterns ◽

Vital Role ◽

Coxsackievirus A16 ◽

Essential Information ◽

Site Distribution ◽

The North ◽

Conformational Epitopes ◽

Enterovirus A71 ◽

Antigenic Evolution

AbstractEnterovirus A71 (EV-A71), Coxsackievirus A16 (CV-A16) and CV-A10 are the major causative agents of hand, foot and mouth disease (HFMD). The conformational epitopes play a vital role in monitoring the antigenic evolution, predicting dominant strains and preparing vaccines. In this study, we employed a Bioinformatics-based algorithm to predict the conformational epitopes of EV-A71 and CV-A16 and compared with that of CV-A10. Prediction results revealed that the distribution patterns of conformational epitopes of EV-A71 and CV-A16 were similar to that of CV-A10 and their epitopes likewise consisted of three sites: site 1 (on the “north rim” of the canyon around the fivefold vertex), site 2 (on the “puff”) and site 3 (one part was in the “knob” and the other was near the threefold vertex). The reported epitopes highly overlapped with our predicted epitopes indicating the predicted results were reliable. These data suggested that three-site distribution pattern may be the basic distribution role of epitopes on the enteroviruses capsids. Our prediction results of EV-A71 and CV-A16 can provide essential information for monitoring the antigenic evolution of enterovirus.

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Response of Severe EV71-Infected Patients to Hyperimmune Plasma Treatment: A Pilot Study

Pathogens ◽

10.3390/pathogens10050625 ◽

2021 ◽

Vol 10 (5) ◽

pp. 625

Author(s):

Chonnamet Techasaensiri ◽

Artit Wongsa ◽

Thanyawee Puthanakit ◽

Kulkanya Chokephaibulkit ◽

Tawee Chotpitayasunondh ◽

...

Keyword(s):

Therapeutic Potential ◽

Antibody Therapy ◽

Foot And Mouth Disease ◽

Neurological Complications ◽

Neurological Involvement ◽

Healthy Donors ◽

Enterovirus A71 ◽

Number Of Patients ◽

Causative Agents ◽

East And Southeast Asia

Hand, foot, and mouth disease (HFMD) is highly prevalent in East and Southeast Asia. It particularly affects children under five years of age. The most common causative agents are coxsackieviruses A6 and A16, and enterovirus A71 (EV71). The clinical presentation is usually mild and self-limited, but, in some cases, severe and fatal complications develop. To date, no specific therapy or worldwide vaccine is available. In general, viral infection invokes both antibody and cell-mediated immune responses. Passive immunity transfer can ameliorate the severe symptoms of diseases such as COVID-19, influenza, MERS, and SARS. Hyperimmune plasma (HIP) from healthy donors with high anti-EV71 neutralizing titer were used to transfuse confirmed EV71-infected children with neurological involvement (n = 6). It resulted in recovery within three days, with no neurological sequelae apparent upon examination 14 days later. Following HIP treatment, plasma chemokines were decreased, whereas anti-inflammatory and pro-inflammatory cytokines gradually increased. Interestingly, IL-6 and G-CSF levels in cerebrospinal fluid declined sharply within three days. These findings indicate that HIP has therapeutic potential for HFMD with neurological complications. However, given the small number of patients who have been treated, a larger cohort study should be undertaken. Successful outcomes would stimulate the development of anti-EV71 monoclonal antibody therapy.

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Fludarabine Inhibits Infection of Zika Virus, SFTS Phlebovirus, and Enterovirus A71

Viruses ◽

10.3390/v13050774 ◽

2021 ◽

Vol 13 (5) ◽

pp. 774

Author(s):

Chengfeng Gao ◽

Chunxia Wen ◽

Zhifeng Li ◽

Shuhan Lin ◽

Shu Gao ◽

...

Keyword(s):

Broad Spectrum ◽

Zika Virus ◽

Therapeutic Agent ◽

Viral Infections ◽

Rna Virus ◽

Emerging Viruses ◽

Enterovirus A71 ◽

Ic50 Values ◽

High Doses ◽

Severe Fever

Viral infections are one of the leading causes in human mortality and disease. Broad-spectrum antiviral drugs are a powerful weapon against new and re-emerging viruses. However, viral resistance to existing broad-spectrum antivirals remains a challenge, which demands development of new broad-spectrum therapeutics. In this report, we showed that fludarabine, a fluorinated purine analogue, effectively inhibited infection of RNA viruses, including Zika virus, Severe fever with thrombocytopenia syndrome virus, and Enterovirus A71, with all IC50 values below 1 μM in Vero, BHK21, U251 MG, and HMC3 cells. We observed that fludarabine has shown cytotoxicity to these cells only at high doses indicating it could be safe for future clinical use if approved. In conclusion, this study suggests that fludarabine could be developed as a potential broad-spectrum anti-RNA virus therapeutic agent.

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Molecular epidemiology and recombination of Enterovirus A71 in mainland China from 1987 to 2017

International Microbiology ◽

10.1007/s10123-021-00164-2 ◽

2021 ◽

Author(s):

Jingyi Zhou ◽

Yingying Shi ◽

Li Miao ◽

Chunyan Zhang ◽

Yongjuan Liu

Keyword(s):

Molecular Epidemiology ◽

Mainland China ◽

Enterovirus A71

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Antiviral activity of Mulberroside C against enterovirus A71 in vitro and in vivo

European Journal of Pharmacology ◽

10.1016/j.ejphar.2021.174204 ◽

2021 ◽

pp. 174204

Author(s):

Yiming Cao ◽

En Lei ◽

Lei Li ◽

Jin Ren ◽

Xiaoyang He ◽

...

Keyword(s):

Antiviral Activity ◽

Enterovirus A71

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Licochalcone A inhibits enterovirus A71 replication in vitro and in vivo

Antiviral Research ◽

10.1016/j.antiviral.2021.105091 ◽

2021 ◽

pp. 105091

Author(s):

Yiming Cao ◽

En Lei ◽

Xiaolong Wang ◽

Xiangyun Qi ◽

Lei Li ◽

...

Keyword(s):

Licochalcone A ◽

Enterovirus A71

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Vaccine candidates generated by codon and codon pair deoptimization of enterovirus A71 protect against lethal challenge in mice

Vaccine ◽

10.1016/j.vaccine.2021.02.024 ◽

2021 ◽

Vol 39 (12) ◽

pp. 1708-1720

Author(s):

Michelle Hui Pheng Lee ◽

Chee Wah Tan ◽

Han Kang Tee ◽

Kien Chai Ong ◽

I-Ching Sam ◽

...

Keyword(s):

Lethal Challenge ◽

Vaccine Candidates ◽

Enterovirus A71 ◽

Codon Pair

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Environmental Surveillance through Next-Generation Sequencing to Unveil the Diversity of Human Enteroviruses beyond the Reported Clinical Cases

Viruses ◽

10.3390/v13010120 ◽

2021 ◽

Vol 13 (1) ◽

pp. 120

Author(s):

Andrés Lizasoain ◽

Daiana Mir ◽

Gisella Masachessi ◽

Adrián Farías ◽

Nélida Rodríguez-Osorio ◽

...

Keyword(s):

Next Generation Sequencing ◽

Next Generation ◽

Echovirus 30 ◽

Coxsackievirus B4 ◽

Important Region ◽

Enterovirus A71 ◽

Wastewater Samples ◽

Valuable Role ◽

Generation Sequencing

The knowledge about circulation of Human Enteroviruses (EVs) obtained through medical diagnosis in Argentina is scarce. Wastewater samples monthly collected in Córdoba, Argentina during 2011–2012, and then in 2017–2018 were retrospectively studied to assess the diversity of EVs in the community. Partial VP1 gene was amplified by PCR from wastewater concentrates, and amplicons were subject of next-generation sequencing and genetic analyses. There were 41 EVs detected, from which ~50% had not been previously reported in Argentina. Most of the characterized EVs (60%) were detected at both sampling periods, with similar values of intratype nucleotide diversity. Exceptions were enterovirus A71, coxsackievirus B4, echovirus 14, and echovirus 30, which diversified in 2017–2018. There was a predominance of types from EV-C in 2017–2018, evidencing a common circulation of these types throughout the year in the community. Interestingly, high genetic similarity was evidenced among environmental strains of echovirus 30 circulating in 2011–2012 and co-temporal isolates obtained from patients suffering aseptic meningitis in different locations of Argentina. This study provides an updated insight about EVs circulating in an important region of South America, and suggests a valuable role of wastewater-based epidemiology in predicting outbreaks before the onset of cases in the community.

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Enterovirus A71 causing meningoencephalitis and acute flaccid myelitis in a patient receiving rituximab

Journal of Neuroimmunology ◽

10.1016/j.jneuroim.2021.577639 ◽

2021 ◽

pp. 577639

Author(s):

Ronak K. Kapadia ◽

Christine M. Gill ◽

Christine Baca ◽

Constance McMenamin ◽

Arun Kannappan ◽

...

Keyword(s):

Acute Flaccid Myelitis ◽

Enterovirus A71

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