Development of Novel Vaccines against Enterovirus-71

Yee, Pinn Tsin Isabel; Poh, Chit Laa

doi:10.3390/v8010001

Cited by 14 publications

(9 citation statements)

References 59 publications

(61 reference statements)

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“…Most EV infections are mild, but tools are required for detecting EVs from clinical samples, including blood, cerebral spinal fluid, stool and in histologic sections in more serious infections. As multiple EV types are linked to diseases like viral myocarditis, encephalitis and type 1 diabetes 1 , 28 , reagents that are capable of detecting a broad range of different EV types with both high specificity and sensitivity are needed.…”

Section: Discussionmentioning

confidence: 99%

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A novel rat CVB1-VP1 monoclonal antibody 3A6 detects a broad range of enteroviruses

Saarinen

Laiho

Richardson

et al. 2018

Sci Rep

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Enteroviruses (EVs) are common RNA viruses that cause diseases ranging from rash to paralytic poliomyelitis. For example, EV-A and EV-C viruses cause hand-foot and mouth disease and EV-B viruses cause encephalitis and myocarditis, which can result in severe morbidity and mortality. While new vaccines and treatments for EVs are under development, methods for studying and diagnosing EV infections are still limited and therefore new diagnostic tools are required. Our aim was to produce and characterize new antibodies that work in multiple applications and detect EVs in tissues and in vitro. Rats were immunized with Coxsackievirus B1 capsid protein VP1 and hybridomas were produced. Hybridoma clones were selected based on their reactivity in different immunoassays. The most promising clone, 3A6, was characterized and it performed well in multiple techniques including ELISA, immunoelectron microscopy, immunocyto- and histochemistry and in Western blotting, detecting EVs in infected cells and tissues. It recognized several EV-Bs and also the EV-C representative Poliovirus 3, making it a broad-spectrum EV specific antibody. The 3A6 rat monoclonal antibody can help to overcome some of the challenges faced with commonly used EV antibodies: it enables simultaneous use of mouse-derived antibodies in double staining and it is useful in murine models.

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Section: Discussionmentioning

confidence: 99%

“…This indicates that recombinant proteins which do not represent the native EV capsid may not be efficient in the generation of antibodies capable of blocking viral infection. The above observations question the rationale of VP1-based subunit vaccines for preventing EV infections 28 .…”

Section: Discussionmentioning

confidence: 99%

A novel rat CVB1-VP1 monoclonal antibody 3A6 detects a broad range of enteroviruses

Saarinen

Laiho

Richardson

et al. 2018

Sci Rep

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“…This is to be expected as the 5′-NTR was responsible for cap-independent translation of viral proteins. The position of a certain specific amino acid in the genome may have a profound significance on virulence [27]. For example, it was reported that the presence of Asn at position 165 of VP2 in the Coxsackievirus B3 was responsible for a cardiovirulent phenotype [28] or virulence could be due to the cooperative effect of several critical amino acids.…”

Section: Discussionmentioning

confidence: 99%

Identification of molecular determinants of cell culture growth characteristics of Enterovirus 71

Yee

Tan

Othman

et al. 2016

Virol J

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BackgroundHand, foot and mouth disease is caused by Enterovirus 71 (EV-A71) and Coxsackieviruses. EV-A71 infection is associated with high fever, rashes and ulcers but more severe symptoms such as cardiopulmonary failure and death have been reported. The lack of vaccines highlighted the urgency of developing preventive agents against EV-A71. The molecular determinants of virulent phenotypes of EV-A71 is unclear. It remains to be investigated if specific molecular determinants would affect the cell culture growth characteristics of the EV-A71 fatal strain in Rhabdomyosarcoma (RD) cells.ResultsIn this study, several genetically modified sub-genotype B4 EV-A71 mutants were constructed by site-directed mutations at positions 158, 475, 486, 487 and 5262 or through partial deletion of the 5′-NTR region (∆ 11 bp from nt 475 to 486) to generate a deletion mutant (PD). EV-A71 mutants 475 and PD caused minimal cytopathic effects, produced lowest viral RNA copy number, viral particles as well as minimal amount of viral protein (VP1) in RD cells when compared to mutants 158, 486, 487 and 5262.ConclusionsThe molecular determinants of virulent phenotypes of EV-A71 sub-genotype B4 strain 41 (5865/Sin/000009) were found to differ from the C158 molecular determinant reported for the fatal EV-A71 sub-genotype B1 strain (clinical isolate 237). The site-directed mutations (SDM) introduced at various sites of the cDNA affected growth of the various mutants when compared to the wild type. Lowest viral RNA copy number, minimal number of plaques formed, higher infectious doses required for 50% lethality of RD cells and much reduced VP1 of the EV-A71 sub-genotype B4 strain 41 genome was attained in mutants carrying SDM at position 475 and through partial deletion of 11 bp at the 5′-NTR region.

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“…After two severe outbreaks in Linyi City in 2007 and Fuyang City in 2008, HFMD has been classified as a Class III notifiable communicable disease by the Chinese government [ 8 , 9 ]. But vaccines and antiviral drugs against EV-A71 or CV-A16 are still on the way to limit the spread of HFMD [ 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

Different responses of weather factors on hand, foot and mouth disease in three different climate areas of Gansu, China

Gou

Liu

et al. 2018

BMC Infect Dis

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BackgroundTo determine the linear and non-linear interacting relationships between weather factors and hand, foot and mouth disease (HFMD) in children in Gansu, China, and gain further traction as an early warning signal based on weather variability for HFMD transmission.MethodWeekly HFMD cases aged less than 15 and meteorological information from 2010 to 2014 in Jiuquan, Lanzhou and Tianshu, Gansu, China were collected. Generalized linear regression models (GLM) with Poisson link and classification and regression trees (CART) were employed to determine the combined and interactive relationship of weather factors and HFMD in both linear and non-linear ways.ResultsGLM suggested an increase in weekly HFMD of 5.9% [95% confidence interval (CI): 5.4%, 6.5%] in Tianshui, 2.8% [2.5%, 3.1%] in Lanzhou and 1.8% [1.4%, 2.2%] in Jiuquan in association with a 1 °C increase in average temperature, respectively. And 1% increase of relative humidity could increase weekly HFMD of 2.47% [2.23%, 2.71%] in Lanzhou and 1.11% [0.72%, 1.51%] in Tianshui. CART revealed that average temperature and relative humidity were the first two important determinants, and their threshold values for average temperature deceased from 20 °C of Jiuquan to 16 °C in Tianshui; and for relative humidity, threshold values increased from 38% of Jiuquan to 65% of Tianshui.ConclusionAverage temperature was the primary weather factor in three areas, more sensitive in southeast Tianshui, compared with northwest Jiuquan; Relative humidity’s effect on HFMD showed a non-linear interacting relationship with average temperature.

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Development of Novel Vaccines against Enterovirus-71

Cited by 14 publications

References 59 publications

A novel rat CVB1-VP1 monoclonal antibody 3A6 detects a broad range of enteroviruses

A novel rat CVB1-VP1 monoclonal antibody 3A6 detects a broad range of enteroviruses

Identification of molecular determinants of cell culture growth characteristics of Enterovirus 71

Different responses of weather factors on hand, foot and mouth disease in three different climate areas of Gansu, China

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