MST1/2 exerts a pivotal role in inducing neuroinflammation and Coxsackievirus-A10 replication by interacting with innate immunity.

Coxsackievirus-A10 (CV-A10), responsible for the hand, foot and mouth disease (HFMD) pandemic, could cause serious central nervous system (CNS) complications. The underlying molecular basis of CV-A10 and host interactions inducing neuropathogenesis is still unclear. The Hippo signaling pathway, historically known for a dominator of organ development and homeostasis, has recently been implicated as an immune regulator. However, its role in host defense against CV-A10 has not been investigated. Herein, it was found that CV-A10 proliferated in HMC3 cells and promoted the release of inflammatory cytokines. Moreover, pattern recognition receptors (PRRs)-mediated pathways, including TLR3-TRIF-TRAF3-TBK1-NF-κB axis, RIG-I/MDA5-MAVS-TRAF3-TBK1-NF-κB axis and TLR7-MyD88-IRAK1/IRAK4-TRAF6-TAK1-NF-κB axis, were examined to be elevated under CV-A10 infection. Meanwhile, it was further uncovered that Hippo signaling pathway was inhibited in HMC3 cells with CV-A10 infection. Previous studies have been reported that there exist complex relations between innate immune and Hippo signaling pathway. Then, plasmids of knockdown and overexpression of MST1/2 were transfected into HMC3 cells. Our results showed that MST1/2 suppressed the levels of inflammatory cytokines via interacting with TBK1 and IRAK1, and also enhanced virus production via restricting IRF3 and IFN-ß expressions. Overall, these data obviously pointed out that CV-A10 accelerated the formation of neuroinflammation by the effect of the Hippo pathway on the PRRs-mediated pathway, which delineates a negative immunoregulatory role for MST1/2 in CV-A10 infection and the potential for this pathway to be pharmacologically targeted to treat CV-A10.

A meta-analysis on the potency of foot-and-mouth disease vaccines in different animal models.

Whether mice can be used as a foot-and-mouth disease (FMD) model has been debated for a long time. However, the major histocompatibility complex between pigs and mice is very different. In this study, the protective effects of FMD vaccines in different animal models were analyzed by a meta-analysis. The databases PubMed, China Knowledge Infrastructure, EMBASE, and Baidu Academic were searched. For this purpose, we evaluated evidence from 14 studies that included 869 animals with FMD vaccines. A random effects model was used to combine effects using Review Manager 5.4 software. A forest plot showed that the protective effects in pigs were statistically non-significant from those in mice [MH = 0.56, 90% CI (0.20, 1.53), P = 0.26]. The protective effects in pigs were also statistically non-significant from those in guinea pigs [MH = 0.67, 95% CI (0.37, 1.21), P = 0.18] and suckling mice [MH = 1.70, 95% CI (0.10, 28.08), P = 0.71]. Non-inferiority test could provide a hypothesis that the models (mice, suckling mice and guinea pigs) could replace pigs as FMDV vaccine models to test the protective effect of the vaccine. Strict standard procedures should be established to promote the assumption that mice and guinea pigs should replace pigs in vaccine evaluation.

Unilateral acute idiopathic maculopathy related to hand-foot-mouth disease: Case report and literature review.

Unilateral acute idiopathic maculopathy (UAIM) is a rare disease that may cause unilateral vision loss in young adults after a flu-like illness. Occasionally, it is associated with hand-foot-mouth disease (HFMD) and is often underdiagnosed. Herein, we report a case with characteristics of UAIM associated with HFMD with acute enteroviral infection. On the basis of the clinical findings using multimodality diagnostic imaging, including fundus image, optical coherence tomography, fluorescence angiography, and serological test for pan-enterovirus RNA polymerase chain reaction, we detailed the clinical course and postulated the pathogenesis of UAIM with choroiditis associated with HFMD. This study could remind every doctor of the potential visual loss caused by UAIM in HFMD, and referring patients to the ophthalmologic survey is important to eliminate potential visual impairment.

Correlation between 146S Antigen Content in Foot-and-Mouth Disease Inactivated Vaccines and Immunogenicity Level and Vaccine Potency Alternative Test Methods.

To investigate the association between 146S antigen contents in FMD inactivated vaccines and levels of antiviral immunity, this study vaccinated 30 kg pigs with three batches of FMD types O and A bivalent inactivated vaccines. Antibody titers and interferon-gamma (IFN-γ) secretion levels were measured on days 7, 14, 21, and 28 after primary immunization and on days 14 and 28 following booster immunization to assess associations between 146S contents and both antibody titers and IFN-γ secretion levels. Furthermore, 30 kg pigs were vaccinated with 46 batches of FMD type O inactivated vaccines and challenged on day 28, after which PD50 values were determined to evaluate the association between 146S content and PD50. The findings suggested that antibody titers and IFN-γ secretion levels at specific time points after immunization were positively associated with 146S contents. Additionally, 146S content showed a positive correlation with PD50, with greater PD50 values recorded for 146S contents ranging from 4.72 to 16.55 µg/dose. This investigation established a significant association between the 146S content in FMD inactivated vaccines and induced immune response against FMDV, thereby emphasizing its critical role in vaccine quality control. The determination of 146S content could serve as a new method for potency testing, offering an alternative to animal challenge tests.

Short-Term Effects of Extreme Meteorological Factors on Hand, Foot, and Mouth Disease Infection During 2010-2017 in Jiangsu, China: A Distributed Lag Non-Linear Analysis.

Hand, Foot, and Mouth Disease (HFMD) is an infectious disease that primarily affects young children. In densely populated Jiangsu Province in China, the impact of extreme meteorological factors on HFMD is a concern. We aimed to examine the association between extreme meteorological variables and HFMD infection risk using daily HFMD infections and meteorological data from 2010 to 2017 in Jiangsu Province. We used distributed lag non-linear model (DLNM) to analyze the data, which can effectively capture the nuanced non-linear dynamics and lag effects in the relationship between HFMD and extreme meteorological factors. Comparing the 10th and 90th percentiles of meteorological variables with their respective median values, our results showed that extremely low temperatures and high humidity were significantly associated with increased HFMD infection risk. The greatest effect of extremely low temperatures was observed at a lag of 1-2 days, elevating the risk by 18 âˆ¼ 33% (RR = 1.18 âˆ¼ 1.33). Extremely high humidity was found to increase the risk of infection, starting at a lag of 4 days. In contrast, extremely high temperatures, low humidity, and high wind speed were associated with reduced risk of infection at lag of 0-12 days, with the range of RR values being 0.60-0.98 for extremely high temperatures, 0.69-0.89 for extremely low humidity, and 0.84-0.98 for extremely high wind speed respectively. Our findings suggest that extreme meteorological factors can significantly impact the incidence of HFMD in Jiangsu Province, and highlight the need for effective public health protection measures during the periods of extreme meteorological condition, particularly for vulnerable populations.

Postvaccination serosurveillance of foot-and-mouth disease through virus-neutralizing and nonstructural protein antibody tests on pig farms in Taiwan: 2009-2020.

The use of virus-neutralizing (VN) and nonstructural protein (NSP) antibody tests in a serosurveillance program for foot-and-mouth disease (FMD) can identify pig herds that are adequately vaccinated, with a high percentage of pigs with VN positive antibody titers; these tests can also help identify pigs with NSP-positivity that have previously been or are currently infected even in vaccinated herds. To identify infected herds and manage infection, the combination of VN and NSP antibody tests was used in Taiwan's serosurveillance program implemented simultaneously with the compulsory FMD vaccination program. The result was the eradication of FMD: Taiwan was recognized by the World Organization for Animal Health as an FMD-free country without vaccination in 2020. Evaluation of the compulsory vaccination program incorporated in the FMD control program in Taiwan revealed that the vaccine quality was satisfactory and the vaccination program was effective during the period of compulsory vaccination (2010-2017). Sound immunological coverage was achieved, with 89.1% of pigs having VN antibody titers exceeding 1:16 in 2016. This level of immunological coverage would be expected to substantially reduce or prevent FMD transmission, which was borne out by the results of the NSP tests. We identified farms having positive NSP reactors (very low annual prevalence) before the cessation of FMD vaccination in July 2018; however, detailed serological and clinical investigations of pigs of all ages in suspect herds demonstrated that no farms were harboring infected animals after the second half of 2013. Thus, the results revealed no evidence of FMD circulation in the field, and Taiwan regained FMD-free status.

Phylodynamic analysis of foot-and-mouth disease virus evolution in Mar Chiquita, Argentina.

Foot-and-mouth disease is a highly contagious disease affecting cloven-hoofed animals, resulting in considerable economic losses. Its causal agent is foot-and-mouth disease virus (FMDV), a picornavirus. Due to its error-prone replication and rapid evolution, the transmission and evolutionary dynamics of FMDV can be studied using genomic epidemiological approaches. To analyze FMDV evolution and identify possible transmission routes in an Argentinean region, field samples that tested positive for FMDV by PCR were obtained from 21 farms located in the Mar Chiquita district. Whole FMDV genome sequences were obtained by PCR amplification in seven fragments and sequencing using the Sanger technique. The genome sequences obtained from these samples were then analyzed using phylogenetic, phylogeographic, and evolutionary approaches. Three local transmission clusters were detected among the sampled viruses. The dataset was analyzed using Bayesian phylodynamic methods with appropriate coalescent and relaxed molecular clock models. The estimated mean viral evolutionary rate was 1.17 × 10- 2 substitutions/site/year. No significant differences in the rate of viral evolution were observed between farms with vaccinated animals and those with unvaccinated animals. The most recent common ancestor of the sampled sequences was dated to approximately one month before the first reported case in the outbreak. Virus transmission started in the south of the district and later dispersed to the west, and finally arrived in the east. Different transmission routes among the studied herds, such as non-replicating vectors and close contact contagion (i.e., aerosols), may be responsible for viral spread.

Enterovirus A71 infection-induced dry eye-like symptoms by damaging the lacrimal glands.

Purpose: To determine the effects of EV-A71 (Enterovirus A71) infection on ocular surface and its mechanism. Methods: AG6 mice aged two to three weeks were randomly divided into control and EV-A71 infected groups. Slit-lamp observation, fluorescein staining, and phenol red thread test were used to assess symptoms of ocular surface at 4 dpi (days post infection). The pathological changes of cornea and lacrimal gland were observed by H&E staining, PAS staining, TUNEL assay, IHC staining and qRT-PCR. Corneas and lacrimal glands from mice were obtained and processed for RNA sequencing analysis. Newly diagnosed HFMD patients caused by EV-A71 were recruited and ensured they met the inclusion criteria. Ocular surface parameters (TMH and NIKBUT) were measured using the OCULUS Keratograph 5M. Tear samples were taken to examine Cxcl1 and IL-6 levels through the ELISA method. Results: Mice studies revealed that EV-A71 infection caused tear film instability, decreased tear secretions, decreased in lacrimal gland size, and distinct goblet cell loss. It also resulted in increased large vacuoles within acinar cells and structural damage in lacrimal gland. Apart from minor damage to the epidermis, there was no obvious inflammatory changes or apoptosis in the cornea. However, there were significant inflammatory injury and apoptosis in the lacrimal gland. RNA-seq analysis showed IL-17 and NF-κB signaling pathways were activated in the lacrimal glands of mice infected with EV-A71. In HFMD patients, the THM was in a low range and NITBUT was significantly shorter than the control group by Oculus Keratograph 5M. ELISA assay showed a higher tear Cxcl1 and IL-6 level in them. Conclusion: EV-A71 infection affected lacrimal gland structure and function and induced dry eye-like symptoms.

Prophylactic treatment with PEGylated bovine IFNλ3 effectively bridges the gap in vaccine-induced immunity against FMD in cattle.

Foot-and-mouth disease (FMD) is a vesicular disease of cloven-hoofed animals with devastating economic implications. The current FMD vaccine, routinely used in enzootic countries, requires at least 7 days to induce protection. However, FMD vaccination is typically not recommended for use in non-enzootic areas, underscoring the need to develop new fast-acting therapies for FMD control during outbreaks. Interferons (IFNs) are among the immune system's first line of defense against viral infections. Bovine type III IFN delivered by a replication defective adenovirus (Ad) vector has effectively blocked FMD in cattle. However, the limited duration of protection-usually only 1-3 days post-treatment (dpt)-diminishes its utility as a field therapeutic. Here, we test whether polyethylene glycosylation (PEGylation) of recombinant bovine IFNλ3 (PEGboIFNλ3) can extend the duration of IFN-induced prevention of FMDV infection in both vaccinated and unvaccinated cattle. We treated groups of heifers with PEGboIFNλ3 alone or in combination with an adenovirus-based FMD O1Manisa vaccine (Adt-O1M) at either 3 or 5 days prior to challenge with homologous wild type FMDV. We found that pre-treatment with PEGboIFNλ3 was highly effective at preventing clinical FMD when administered at either time point, with or without co-administration of Adt-O1M vaccine. PEGboIFNλ3 protein was detectable systemically for >10 days and antiviral activity for 4 days following administration. Furthermore, in combination with Adt-O1M vaccine, we observed a strong induction of FMDV-specific IFNγ+ T cell response, demonstrating its adjuvanticity when co-administered with a vaccine. Our results demonstrate the promise of this modified IFN as a pre-exposure prophylactic therapy for use in emergency outbreak scenarios.

Impact of the COVID-19 outbreak and interventions on hand, foot and mouth disease in Zhengzhou, China, 2014-2022: a retrospective study.

BACKGROUND: Since December 2019, COVID-19 has spread rapidly around the world, and studies have shown that measures to prevent COVID-19 can largely reduce the spread of other infectious diseases. This study explored the impact of the COVID-19 outbreak and interventions on the incidence of HFMD. METHODS: We gathered data on the prevalence of HFMD from the Children's Hospital Affiliated to Zhengzhou University. An autoregressive integrated moving average model was constructed using HFMD incidence data from 2014 to 2019, the number of cases predicted from 2020 to 2022 was predicted, and the predicted values were compared with the actual measurements. RESULTS: From January 2014 to October 2022, the Children's Hospital of Zhengzhou University admitted 103,995 children with HFMD. The average number of cases of HFMD from 2020 to 2022 was 4,946, a significant decrease from 14,859 cases from 2014 to 2019. We confirmed the best ARIMA (2,0,0) (1,1,0)12 model. From 2020 to 2022, the yearly number of cases decreased by 46.58%, 75.54%, and 66.16%, respectively, compared with the forecasted incidence. Trends in incidence across sexes and ages displayed patterns similar to those overall. CONCLUSIONS: The COVID-19 outbreak and interventions reduced the incidence of HFMD compared to that before the outbreak. Strengthening public health interventions remains a priority in the prevention of HFMD.

Ensemble learning methods of inference for spatially stratified infectious disease systems.

Individual level models are a class of mechanistic models that are widely used to infer infectious disease transmission dynamics. These models incorporate individual level covariate information accounting for population heterogeneity and are generally fitted in a Bayesian Markov chain Monte Carlo (MCMC) framework. However, Bayesian MCMC methods of inference are computationally expensive for large data sets. This issue becomes more severe when applied to infectious disease data collected from spatially heterogeneous populations, as the number of covariates increases. In addition, summary statistics over the global population may not capture the true spatio-temporal dynamics of disease transmission. In this study we propose to use ensemble learning methods to predict epidemic generating models instead of time consuming Bayesian MCMC method. We apply these methods to infer disease transmission dynamics over spatially clustered populations, considering the clusters as natural strata instead of a global population. We compare the performance of two tree-based ensemble learning techniques: random forest and gradient boosting. These methods are applied to the 2001 foot-and-mouth disease epidemic in the U.K. and evaluated using simulated data from a clustered population. It is shown that the spatially clustered data can help to predict epidemic generating models more accurately than the global data.

Circulation of foot-and-mouth disease serotypes, risk factors, and their effect on hematological and biochemical profiles among cattle and buffalo in Quetta, Balochistan, Pakistan.

Background and Aim: Foot-and-mouth disease (FMD) is an infectious disease of cloven-hoofed animals, including buffalo, cattle, sheep, goats, and pigs, causing major economic losses to the local farmers and, overall, to the national economy of the country. This study aimed to detect FMDV serotypes in year-round FMD outbreaks, hematological and biochemical changes, and oxidative stress in FMDV-infected cattle and buffaloes in the district of Quetta, Balochistan, Pakistan, and the socioeconomic impact of FMD outbreaks on farmers. Materials and Methods: We conducted a cross-sectional study in the district of Quetta, Balochistan, Pakistan, where FMD virus (FMDV) serotypes were detected by enzyme-linked immunosorbent assay (ELISA). Hematological, biochemical, and oxidative analyses were performed by analyzing the blood of FMDV-infected and non-infected animals. Information on the associated risk factors was obtained through a structured questionnaire by interviewing farmers in each FMD-affected farm. Results: Thirty-four out of 38 farms (89%, 95% confidence interval [CI]: 75%-97%) were positive for FMD by ELISA. Higher FMD infection was detected in farms with a herd size of <50 animals (50%, 17/34), followed by >100 animals (32%, 11/34) and 51-100 animals (18%, 6/34). Fifty-seven percent (114/200, 95% CI: 50%-64%) of animals were positive for FMD. Of these, 61% (69/114) were cattle and 39% (45/114) were buffalo. FMD positivity was higher in females (86%, 98/114) than in males (14%, 16/114) and higher in animals older than 2 years of age (52%, 59/114). On average, farmers lose U.S. dollars 3000 annually due to FMD outbreaks. Animals infected with FMDV had significantly (p ≤ 0.05) white blood cell counts and significantly (p ≤ 0.05) lower hemoglobin and total protein concentrations in buffalo and cattle, whereas infected cattle showed significantly (p ≤ 0.05) lower albumin levels. Globulin levels were lower in buffaloes infected. Alanine aminotransferase levels were lower in infected cattle (p ≤ 0.05). Creatinine levels were higher in infected buffalo (p ≤ 0.05). Urea and phosphorus concentrations were higher in FMDV-infected cattle and buffalo (p ≤ 0.05). Calcium levels were lower in infected cattle and buffalo (p ≤ 0.05). Catalase enzyme activity in infected cattle and buffaloes was significantly lower (p < 0.05). Lipid peroxidation was significantly higher in FMDV-infected cattle and buffalo (p ≤ 0.05). Conclusion: This study confirmed serotype O circulation among cattle and buffalo in year-long FMD outbreaks in the Quetta District of Balochistan. Blood analysis identified a parameter deviated from the normal level due to FMDV infection. In addition, the outbreak of FMD has a significant negative economic impact on livestock farmers.

A comparison of risk factor investigation and experts' opinion elicitation analysis for identifying foot-and-mouth disease (FMD) high-risk areas within the FMD protection zone of South Africa (2007-2016).

Foot-and-mouth disease is a controlled disease in accordance with the South African Animal Diseases Act (Act 35 of 1984). The country was classified by the World Organisation for Animal Health (WOAH) as having a FMD free zone without vaccination in 1996. However, this status was suspended in 2019 due to a FMD outbreak outside the controlled zones. FMD control in South Africa includes animal movement restrictions placed on cloven-hoofed species and products, prophylactic vaccination of cattle, clinical surveillance of susceptible species, and disease control fencing to separate livestock from wildlife reservoirs. The objectives of this study were to evaluate differences in identifying high-risk areas for FMD using risk factor and expert opinion elicitation analysis. Differences in risk between FMD introduction and FMD spread within the FMD protection zone with vaccination (PZV) of South Africa (2007-2016) were also investigated. The study was conducted in the communal farming area of the FMD PZV, which is adjacent to wildlife reserves and characterised by individual faming units. Eleven risk factors that were considered important for FMD occurrence and spread were used to build a weighted linear combination (WLC) score based on risk factor data and expert opinion elicitation. A multivariable conditional logistic regression model was also used to calculate predicted probabilities of a FMD outbreak for all dip-tanks within the study area. Smoothed Bayesian kriged maps were generated for 11 individual risk factors, overall WLC scores for FMD occurrence and spread and for predicted probabilities of a FMD outbreak based on the conditional logistic regression model. Descriptively, vaccine matching was believed to have a great influence on both FMD occurrence and spread. Expert opinion suggested that FMD occurrence was influenced predominantly by proximity to game reserves and cattle density. Cattle populations and vaccination practices were considered most important for FMD spread. Highly effective cattle inspections were observed within areas that previously reported FMD outbreaks, indicating the importance of cattle inspection (surveillance) as a necessary element of FMD outbreak detection. The multivariable conditional logistic regression analysis, which was consistent with expert opinion elicitation; identified three factors including cattle population density (OR 3.87, 95% CI 1.47-10.21) and proximities to game reserve fences (OR 0.82, 95% CI 0.73-0.92) and rivers (OR 1.04, 95% CI 1.01-1.07) as significant factors for reported FMD outbreaks. Regaining and maintaining an FMD-free status without vaccination requires frequent monitoring of high-risk areas and designing targeted surveillance.

Modeling target-density-based cull strategies to contain foot-and-mouth disease outbreaks.

Total ring depopulation is sometimes used as a management strategy for emerging infectious diseases in livestock, which raises ethical concerns regarding the potential slaughter of large numbers of healthy animals. We evaluated a farm-density-based ring culling strategy to control foot-and-mouth disease (FMD) in the United Kingdom (UK), which may allow for some farms within rings around infected premises (IPs) to escape depopulation. We simulated this reduced farm density, or "target density", strategy using a spatially-explicit, stochastic, state-transition algorithm. We modeled FMD spread in four counties in the UK that have different farm demographics, using 740,000 simulations in a full-factorial analysis of epidemic impact measures (i.e., culled animals, culled farms, and epidemic length) and cull strategy parameters (i.e., target farm density, daily farm cull capacity, and cull radius). All of the cull strategy parameters listed above were drivers of epidemic impact. Our simulated target density strategy was usually more effective at combatting FMD compared with traditional total ring depopulation when considering mean culled animals and culled farms and was especially effective when daily farm cull capacity was low. The differences in epidemic impact measures among the counties are likely driven by farm demography, especially differences in cattle and farm density. To prevent over-culling and the associated economic, organizational, ethical, and psychological impacts, the target density strategy may be worth considering in decision-making processes for future control of FMD and other diseases.

Foot-and-Mouth Disease.

Foot-and-mouth disease (FMD) is a viral infection of livestock that is an important determinant of global trade in animal products. The disease causes a highly contagious vesicular syndrome of cloven-hoofed animals. Successful control of FMD is dependent upon early detection and recognition of the clinical signs, followed by appropriate notification and response of responsible government entities. Awareness of the clinical signs of FMD amongst producers and veterinary practitioners is therefore the key in protecting US agriculture from the catastrophic impacts of an FMD outbreak. This review summarizes key clinical and epidemiologic features of FMD from a US perspective.

The Global Framework for the Progressive Control of Transboundary Animal Diseases - Strengthening Infectious Disease Management and Veterinary Systems Across the Continents: Origins and Testimony.

Transboundary animal diseases are defined by the Food and Agriculture Organization (FAO) of the United Nation's Emergency Prevention System as those diseases that are of significant economic, trade and/or food security importance, which can easily spread to other countries and reach epidemic proportions, and where control/management including exclusion requires cooperation among several countries. The Global Framework for the Progressive Control of Transboundary Animal Diseases represents a platform of the FAO and World Organisation for Animal Health to engage regional sub-regional organizations and national veterinary authorities in developing and monitoring progress in animal disease management efforts.

Determination of Optimal Antigen Yield and Virus Inactivation Conditions for the Production of the Candidate Foot-and-Mouth Disease Recombinant Vaccine Strain Asia1 Shamir-R in a Bioreactor.

Since the foot-and-mouth disease (FMD) outbreak in South Korea in 2010-2011, vaccination policies utilizing inactivated FMD vaccines composed of types O and A have been implemented nationwide. However, because type Asia1 occurred in North Korea in 2007 and intermittently in neighboring countries, the risk of type Asia1 introduction cannot be ruled out. This study evaluated the antigen yield and viral inactivation kinetics of the recombinant Asia1 Shamir vaccine strain (Asia1 Shamir-R). When Asia1 Shamir-R was proliferated in shaking flasks (1 L), a 2 L bioreactor (1 L), and a wave bioreactor (25 L), the antigen yields were 7.5 µg/mL, 5.2 µg/mL, and 3.8 µg/mL, respectively. The optimal FMDV inactivation conditions were 2 mM BEI at 26 °C and 1.0 mM BEI at 37 °C. There was no antigen loss due to BEI treatment, and only a decrease in antigen levels was observed during storage. The sera from pigs immunized with antigen derived from a bioreactor exhibited a neutralizing antibody titer of approximately 1/1000 against Asia1 Shamir and Asia1/MOG/05 viruses; therefore, Asia1 Shamir-R is expected to provide sufficient protection against both viruses. If an FMD vaccine production facility is established, this Asia1 Shamir-R can be employed for domestic antigen banks in South Korea.

In-process quality control in foot-and-mouth disease vaccine production by detection of viral non-structural proteins using chemiluminescence dot blot assay.

Foot-and-mouth disease (FMD) is a contagious viral disease of cloven-footed animals. Immunization with inactivated virus vaccine is effective to control the disease. Six-monthly vaccination regimen in endemic regions has proven to be effective. To enable the differentiation of infected animals from those vaccinated, non-structural proteins (NSPs) are excluded during vaccine production. While the antibodies to structural proteins (SPs) could be observed both in vaccinated and infected animals, NSP antibodies are detectable only in natural infection. Quality control assays that detect NSPs in vaccine antigen preparations, are thus vital in the FMD vaccine manufacturing process. In this study, we designed a chemiluminescence dot blot assay to detect the 3A and 3B NSPs of FMDV. It is sensitive enough to detect up to 20 ng of the NSP, and exhibited specificity as it does not react with the viral SPs. This cost-effective assay holds promise in quality control assessment in FMD vaccine manufacturing.

Effectiveness of enterovirus A71 vaccine against pediatric HFMD and disease profile of post-vaccination infection.

BACKGROUND: Vaccination has been proven effective against infection with enterovirus A71 (EV-A71) in clinical trials, but vaccine effectiveness in real-world situations remains incompletely understood. Furthermore, it is not clear whether previous vaccination will result in symptom attenuation among post-vaccinated cases. METHODS: Based on long-term data extracted from the only designed referral hospital for infectious diseases, we used a test-negative case-control design and multivariate logistic regression models to analyze the effectiveness of EV-A71 vaccine against hand, foot and mouth disease (HFMD). And then, generalized linear regression models were used to evaluate the associations between prior vaccination and disease profiles. RESULTS: We selected 4883 inpatients for vaccine efficacy estimations and 2188 inpatients for disease profile comparisons. Vaccine effectiveness against EV-A71-induced HFMD for complete vaccination was 63.4 % and 51.7 % for partial vaccination. The vaccine effectiveness was higher among cases received the first dose within 12 months. No protection was observed against coxsackievirus (CV) A6-, CV-A10- or CV-A16-associated HFMD among children regardless of vaccination status. Completely vaccinated cases had shorter hospital stay and disease course compared to unvaccinated cases (P < 0.05). CONCLUSIONS: These findings reiterate the need to continue the development of a multivalent vaccine or combined vaccines, and have implications for introducing optimized vaccination strategies.

D-galacto-D-mannan-mediated Dectin-2 activation orchestrates potent cellular and humoral immunity as a viral vaccine adjuvant.

Introduction: Conventional foot-and-mouth disease (FMD) vaccines have been developed to enhance their effectiveness; however, several drawbacks remain, such as slow induction of antibody titers, short-lived immune response, and local side effects at the vaccination site. Therefore, we created a novel FMD vaccine that simultaneously induces cellular and humoral immune responses using the Dectin-2 agonist, D-galacto-D-mannan, as an adjuvant. Methods: We evaluated the innate and adaptive (cellular and humoral) immune responses elicited by the novel FMD vaccine and elucidated the signaling pathway involved both in vitro and in vivo using mice and pigs, as well as immune cells derived from these animals. Results: D-galacto-D-mannan elicited early, mid-, and long-term immunity via simultaneous induction of cellular and humoral immune responses by promoting the expression of immunoregulatory molecules. D-galacto-D-mannan also enhanced the immune response and coordinated vaccine-mediated immune response by suppressing genes associated with excessive inflammatory responses, such as nuclear factor kappa B, via Sirtuin 1 expression. Conclusion: Our findings elucidated the immunological mechanisms induced by D-galacto-D-mannan, suggesting a background for the robust cellular and humoral immune responses induced by FMD vaccines containing D-galacto-D-mannan. Our study will help to facilitate the improvement of conventional FMD vaccines and the design of next-generation FMD vaccines.