• Biomolecules & Therapeutics
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• v.31 no.3
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• pp.350-358
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• 2023

Hand-foot-and-mouth disease (HFMD) is a viral infectious disease that occurs in children under 5 years of age. Its main causes are coxsackievirus (CV) and enterovirus (EV). Since there are no efficient therapeutics for HFMD, vaccines are effective in preventing the disease. To develop broad coverage against CV and EV, the development of a bivalent vaccine form is needed. The Mongolian gerbil is an efficient and suitable animal model of EV71 C4a and CVA16 infection used to investigate vaccine efficacy following direct immunization. In this study, Mongolian gerbils were immunized with a bivalent inactivated EV71 C4a and inactivated CVA16 vaccine to test their effectiveness against viral infection. Bivalent vaccine immunization resulted in increased Ag-specific IgG antibody production; specifically, EV71 C4a-specific IgG was increased with medium and high doses and CVA16-specific IgG was increased with all doses of immunization. When gene expression of T cell-biased cytokines was analysed, Th1, Th2, and Th17 responses were found to be highly activated in the high-dose immunization group. Moreover, bivalent vaccine immunization mitigated paralytic signs and increased the survival rate following lethal viral challenges. When the viral RNA content was determined from various organs, all three doses of bivalent vaccine immunization were found to significantly decrease viral amplification. Upon histologic examination, EV71 C4a and CVA16 induced tissue damage to the heart and muscle. However, bivalent vaccine immunization alleviated this in a dose-dependent manner. These results suggest that the bivalent inactivated EV71 C4a/CVA16 vaccine could be a safe and effective candidate HFMD vaccine.

• Korean Journal of Veterinary Service
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• v.41 no.1
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• pp.9-13
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• 2018

The best way to prevent foot-and-mouth disease (FMD) constantly occurring in Korea will be vaccination. In this study, FMD vaccines were given to Korean native cattle (Hanwoo), dairy cattle, and pigs to investigate the antibody positive rate of FMD vaccine by age in year and month. Hanwoo, dairy cattle, and pigs showed antibody positive rates of 99.5%, 97.7%, and 95.9%, respectively. High antibody positive rates more than 95% were found in Hanwoo and dairy cattle. In particular, high antibody positive rates were found in Hanwoo and dairy cattle regardless of age. Pigs showed a relatively low antibody positive rate of 57.6% at 3 months of age and then constantly maintained a high antibody positive rate of above 95.0% after 4 months of age. As a result of this study, high antibody positive rates were found when regular FMD vaccination was given to newborn calves and piglets after FMD vaccination twice to them. Therefore, it is considered the most important to receive vaccination thoroughly according to vaccination plan in order to prevent FMD.

• Clinical and Experimental Pediatrics
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• v.58 no.3
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• pp.112-115
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• 2015

Hand, foot, and mouth disease (HFMD) is an acute, mostly self-limiting infection. Patients usually recover without any sequelae. However, a few cases are life threatening, especially those caused by enterovirus 71 (EV71). A 12-month-old boy was admitted to a primary hospital with high fever and vesicular lesions of the mouth, hands, and feet. After 3 days, he experienced 3 seizure episodes and was referred to our hospital. On admission, he was conscious and his chest radiograph was normal. However, 6 hours later, he suddenly lost consciousness and had developed a massive pulmonary hemorrhage that continued until his death. He experienced several more intermittent seizures, and diffuse infiltration of both lung fields was observed on chest radiography. Intravenous immunoglobulin, dexamethasone, cefotaxime, leukocyte-depleted red blood cells, fresh frozen plasma, inotropics, vitamin K, and endotracheal epinephrine were administered. The patient died 9 hours after intubation, within 3 days from fever onset. EV71 subgenotype C4a was isolated retrospectively from serum and nasopharyngeal swab by real-time reverse transcription-polymerase chain reaction. Here, we report a fatal case of EV71-associated HFMD with sudden-onset massive pulmonary hemorrhage and suspected encephalitis.

• IMMUNE NETWORK
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• v.9 no.6
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• pp.265-273
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• 2009

Foot-and-mouth disease virus (FMDV) is a small single-stranded RNA virus which belongs to the family Picornaviridae, genus Apthovirus. It is a principal cause of FMD which is highly contagious in livestock. In a wild type virus infection, infected animals usually elicit antibodies against structural and non-structural protein of FMDV. A structural protein, VP1, is involved in neutralization of virus particle, and has both B and T cell epitopes. A RNA-dependent RNA polymerase, 3D, is highly conserved among other serotypes and strongly immunogenic, therefore, we selected VP1 and 3D as vaccine targets. VP1 and 3D genes were codon-optimized to enhance protein expression level and cloned into mammalian expression vector. To produce recombinant protein, VP1 and 3D genes were also cloned into pET vector. The VP1 and 3D DNA or proteins were co-immunized into 5 weeks old BALB/C mice. Antigen-specific serum antibody (Ab) responses were detected by Ab ELISA. Cellular immune response against VP1 and 3D was confirmed by ELISpot assay. The results showed that all DNA- and protein-immunized groups induced cellular immune responses, suggesting that both DNA and recombinant protein vaccine administration efficiently induced Ag-specific humoral and cellular immune responses.

• Biomolecules & Therapeutics
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• v.22 no.1
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• pp.41-46
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• 2014

Enterovirus 71 (EV71) is the predominant cause of hand, foot and mouth disease (HFMD). The antiviral activity of hederasaponin B from Hedera helix against EV71 subgenotypes C3 and C4a was evaluated in vero cells. In the current study, the antiviral activity of hederasaponin B against EV71 C3 and C4a was determined by cytopathic effect (CPE) reduction method and western blot assay. Our results demonstrated that hederasaponin B and 30% ethanol extract of Hedera helix containing hederasaponin B showed significant antiviral activity against EV71 subgenotypes C3 and C4a by reducing the formation of a visible CPE. Hederasaponin B also inhibited the viral VP2 protein expression, suggesting the inhibition of viral capsid protein synthesis.These results suggest that hederasaponin B and Hedera helix extract containing hederasaponin B can be novel drug candidates with broad-spectrum antiviral activity against various subgenotypes of EV71.

• Clinical and Experimental Vaccine Research
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• v.13 no.2
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• pp.132-145
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• 2024

Purpose: Enterovirus 71, a pathogen that causes hand-foot and mouth disease (HFMD) is currently regarded as an increasing neurotropic virus in Asia and can cause severe complications in pediatric patients with blister-like sores or rashes on the hand, feet, and mouth. Notwithstanding the significant burden of the disease, no authorized vaccine is available. Previously identified attenuated and inactivated vaccines are worthless over time owing to changes in the viral genome. Materials and Methods: A novel vaccine construct using B-cell derived T-cell epitopes from the virulent polyprotein found the induction of possible immune response. In order to boost the immune system, a beta-defensin 1 preproprotein adjuvant with EAAAK linker was added at the N-terminal end of the vaccine sequence. Results: The immunogenicity of the designed, refined, and verified prospective three-dimensional-structure of the multi-epitope vaccine was found to be quite high, exhibiting non-allergenic and antigenic properties. The vaccine candidates bound to toll-like receptor 3 in a molecular docking analysis, and the efficacy of the potential vaccine to generate a strong immune response was assessed through in silico immunological simulation. Conclusion: Computational analysis has shown that the proposed multi-epitope vaccine is possibly safe for use in humans and can elicit an immune response.

• Clinical and Experimental Vaccine Research
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• v.12 no.4
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• pp.291-297
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• 2023

Enterovirus infections induce infectious diseases in young children, such as hand, foot, and mouth disease which is characterized by highly contagious rashes or blisters around the hands, feet, buttocks, and mouth. This predominantly arises from enterovirus A71 or coxsackievirus A16 infections and in severe cases, they can lead to encephalitis, paralysis, pulmonary edema, or even fatality, representing a global health threat. Due to the absence of effective therapeutic strategies for these infections, various experimental animal models are being investigated for the development of vaccines. During the early stages of research on enterovirus infections, non-human primate infections exhibited symptoms like those in humans, leading to their utilization as model animals. However, due to economic and ethical considerations, their current usage is limited. While enterovirus infections do not readily occur in mice, an infection model with mouse-adapted strain in neonatal mice has been employed. Cellular receptors have been identified in human cells, and genetically modified mice expressing these receptors have been used. Most recently, the utilization of Mongolian gerbil model is actively being considered and should be pursued for further animal model development. So, herein, we provide a summarized overview of the current portfolio of available enterovirus infection models, emphasizing their respective advantages and limitations.

• Korean Journal of Veterinary Research
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• v.49 no.3
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• pp.221-229
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• 2009

Foot-and-mouth disease (FMD) is the most contagious disease of mammals. The use of inactivated vaccine can be chosen to prevent or control FMD. However, vaccination against one serotype of FMDV doses not cross-protect against other serotypes and may not protect fully against some strains of the same serotype. Appropriate selection of vaccine strain is an important element in the control of FMD. The immunity of vaccine antigens should be matched against newly circulating viruses. The phylogenetic analysis of serotype Asia1 reported from China, Mongolia, North Korea and Russia since 2005 shows that they are all classified into genetic group V, but the strain, Asia1/Shamir (ISR/89) which have been used as a vaccine strain in Korea, is clustered into different genetic group. So, in this study the serological relationship between the isolate (Asia1/MOG/05; MOG) and the Shamir strain was determined by ELISA and virus neutralization test. Even though the matching value of the virus (MOG) against the vaccinated sera in target animals was not so high, the vaccinated animals elicited antibodies enough for protection after vaccinated once or twice. Conclusively, we suggest that the vaccine containing Asia1/Shamir antigen could protect the genetic group V strains circulating in East Asia currently if vaccinated twice or the more.

• Food Science of Animal Resources
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• v.38 no.3
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• pp.498-505
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• 2018

This study was aimed to investigate the effects of the type O foot-and-mouse disease vaccine (FMDV) on the incidence of abnormal meat such as granuloma or abscess formation at the injection site in pork and its associated economic losses. At 56 d of age, piglets were inoculated with FMDV by one of three administration routes: N-Neck (a conventional needle-syringe injection into the neck), N-Ham (a conventional needle-syringe injection into the ham), and Non-Neck (injection with a needle-free device into the neck). The injection sites were visually examined for the presence of a granuloma or abscess, and the incidence rate of abnormal meat was calculated. The gross weight of the portion of the pork carcasses condemned because of granuloma or abscess formation was measured and multiplied by the weekly sales price to calculate the total economic losses. After implementation of FMDV, the economic losses were approximately six times higher than before implementation. Granuloma or abscess formation was significantly higher in the N-Neck and Non-Neck groups, in which the vaccine was inoculated into the neck area, than in the N-Ham group (N-Neck and N-Ham vs Non-Neck, p<0.05). These results suggest that the incidence of lesions could be reduced if the ham route was used for vaccination.

• Korean Journal of Veterinary Service
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• v.36 no.1
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• pp.15-21
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• 2013

Three serotypes (O+A+Asia1 type) of the foot-and-mouth disease (FMD) vaccine were injected into cloven-hoofed animals in Korea after the nationwide spread of FMD at the end of 2010. This study was conducted to investigate FMD antibody development after FMD vaccination, and to determine whether there was a significant correlation between the antibody titer of the sow and the antibody titer of the growing pigs. The antibody titer (percentage inhibition [PI] titer) of the sow (gilt) after FMD vaccination was maintained at a level higher than 50 (P<0.05) for 5 months. A higher PI titer for the 1-month-old growing pigs corresponded with greater inhibition of the PI titer of the vaccinated growing pigs (P<0.05). A negative correlation (P<0.05) between the PI titer of the 1-month-old growing pigs and the PI titer of 3-month-old growing pigs, 4-month-old growing pigs after FMD vaccination at 2 months, 3months was identified, with a coefficient of determination ($R^2$) of 0.274. Thus the PI titer of the growing pigs was inhibited to a greater degree when vaccination was performed at 2 months of age than at 3 months. However, many other factors likely influence growing pigs' PI titer in addition to the PI titer of the sow and age at vaccination, given that the coefficient of determination was somewhat lower.