Research

30 pages, 4617 KiB

Open AccessArticle

Host-Specific Interplay between Foot-and-Mouth Disease Virus 3D Polymerase and the Type-I Interferon Pathway

by Morgan Sarry, Grégory Caignard, Juliette Dupré, Stephan Zientara, Damien Vitour, Labib Bakkali Kassimi and Sandra Blaise-Boisseau

Viruses 2023, 15(3), 666; https://doi.org/10.3390/v15030666 - 01 Mar 2023

Cited by 3 | Viewed by 1541 | Correction

Abstract

Foot-and-mouth disease (FMD) is a highly contagious viral disease affecting cloven-hoofed animals. One of the issues related to this disease is the persistence of its causative agent, foot-and-mouth disease virus (FMDV). While the mechanisms of FMDV persistence remain unclear, there are clues that [...] Read more.

Foot-and-mouth disease (FMD) is a highly contagious viral disease affecting cloven-hoofed animals. One of the issues related to this disease is the persistence of its causative agent, foot-and-mouth disease virus (FMDV). While the mechanisms of FMDV persistence remain unclear, there are clues that it may be related to protein–protein interactions (PPI) between viral proteins and cellular proteins involved in the interferon (IFN) response. Since FMDV persistence has been described in cattle, sheep and goats but not in swine, we screened PPI involving FMDV proteins and sixteen major type-I IFN pathway proteins from these four species by nanoluciferase-2-hybrid complementation assay, in order to identify new PPI and determine their host specificity. As the results concerning the 3D^pol were the most interesting in view of the limited data concerning its role in immune escape, we decided to focus particularly on this protein. The identified PPI were confirmed by GST pull-down. We identified PPI between 3D^pol and seven IFN pathway proteins, namely, IKKα, IKKε, IRF3, IRF7, NEMO, MDA5 and MAVS. These PPI are conserved among the four studied species, with the exception of the one between 3D^pol and MAVS, which was only found with the swine protein. We also showed, using luciferase reporter assays, that 3D^pol could inhibit the induction phase of the IFN pathway. These results demonstrate, for the first time, a putative role for 3D^pol in FMDV innate immune escape. Full article

(This article belongs to the Special Issue Global Foot-and-Mouth Disease Control)

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12 pages, 2167 KiB

Open AccessArticle

Insights into the Molecular Epidemiology of Foot-and-Mouth Disease Virus in Russia, Kazakhstan, and Mongolia in Terms of O/ME-SA/Ind-2001e Sublineage Expansion

by Viktor Nikiforov, Alexey Shcherbakov, Ilya Chvala, Svetlana Kremenchugskaya, Fedor Korennoy, Tamara Mayorova, Anna Timina, Samat Tyulegenov, Sarsenbay Abdrakhmanov, Maksat Berdikulov, Tserenchimed Sainnokhoi, Delgerzul Gombo-Ochir, Tsagaan Tserenchimed, Larisa Prokhvatilova and Alexander Sprygin

Viruses 2023, 15(3), 598; https://doi.org/10.3390/v15030598 - 21 Feb 2023

Cited by 2 | Viewed by 1561

Abstract

Foot-and-mouth disease (FMD) has long been recognized as a highly contagious, transboundary disease of livestock incurring substantial losses and burdens to animal production and trade across Africa, the Middle East, and Asia. Due to the recent emergence of the O/ME-SA/Ind-2001 lineage globally contributing [...] Read more.

Foot-and-mouth disease (FMD) has long been recognized as a highly contagious, transboundary disease of livestock incurring substantial losses and burdens to animal production and trade across Africa, the Middle East, and Asia. Due to the recent emergence of the O/ME-SA/Ind-2001 lineage globally contributing to the expansion of FMD, molecular epidemiological investigations help in tracing the evolution of foot-and-mouth disease virus (FMDV) across endemic and newly affected regions. In this work, our phylogenetic analysis reveals that the recent FMDV incursions in Russia, Mongolia, and Kazakhstan in 2021–2022 were due to the virus belonging to the O/ME-SA/Ind-2001e sublineage, belonging to the cluster from Cambodian FMDV isolates. The studied isolates varied by 1.0–4.0% at the VP1 nucleotide level. Vaccine matching tests indicated that the vaccination policy in the subregion should be tailored according to the peculiarities of the ongoing epidemiologic situation. The current vaccination should change from such vaccine strains as O₁ Manisa (ME–SA), O no 2102/Zabaikalsky/2010 (O/ME-SA/Mya-98) (r₁ = 0.05–0.28) to strains that most closely antigenically match the dominant lineage O No. 2212/Primorsky/2014 (O O/ME-SA//Mya-98) and O No. 2311/Zabaikalsky/2016 (O ME-SA/Ind-2001) (r₁ = 0.66–1.0). Full article

(This article belongs to the Special Issue Global Foot-and-Mouth Disease Control)

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18 pages, 2339 KiB

Open AccessArticle

Establishing an In Vitro System to Assess How Specific Antibodies Drive the Evolution of Foot-and-Mouth Disease Virus

by David J. King, Graham Freimanis, Chris Neil, Andrew Shaw, Tobias J. Tuthill, Emma Laing, Donald P. King and Lidia Lasecka-Dykes

Viruses 2022, 14(8), 1820; https://doi.org/10.3390/v14081820 - 19 Aug 2022

Cited by 3 | Viewed by 2189 | Correction

Abstract

Viruses can evolve to respond to immune pressures conferred by specific antibodies generated after vaccination and/or infection. In this study, an in vitro system was developed to investigate the impact of serum-neutralising antibodies upon the evolution of a foot-and-mouth disease virus (FMDV) isolate. [...] Read more.

Viruses can evolve to respond to immune pressures conferred by specific antibodies generated after vaccination and/or infection. In this study, an in vitro system was developed to investigate the impact of serum-neutralising antibodies upon the evolution of a foot-and-mouth disease virus (FMDV) isolate. The presence of sub-neutralising dilutions of specific antisera delayed the onset of virus-induced cytopathic effect (CPE) by up to 44 h compared to the untreated control cultures. Continued virus passage with sub-neutralising dilutions of these sera resulted in a decrease in time to complete CPE, suggesting that FMDV in these cultures adapted to escape immune pressure. These phenotypic changes were associated with three separate consensus-level non-synonymous mutations that accrued in the viral RNA-encoding amino acids at positions VP2⁶⁶, VP2⁸⁰ and VP1¹⁵⁵, corresponding to known epitope sites. High-throughput sequencing also identified further nucleotide substitutions within the regions encoding the leader (L^pro), VP4, VP2 and VP3 proteins. While association of the later mutations with the adaptation to immune pressure must be further verified, these results highlight the multiple routes by which FMDV populations can escape neutralising antibodies and support the application of a simple in vitro approach to assess the impact of the humoral immune system on the evolution of FMDV and potentially other viruses. Full article

(This article belongs to the Special Issue Global Foot-and-Mouth Disease Control)

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18 pages, 3030 KiB

Open AccessArticle

Assessment on Different Vaccine Formulation Parameters in the Protection against Heterologous Challenge with FMDV in Cattle

by Sebastián Di Giacomo, Danilo Bucafusco, Juan Manuel Schammas, Juan Pega, María Cruz Miraglia, Florencia Barrionuevo, Alejandra Victoria Capozzo and Daniel Mariano Perez-Filgueira

Viruses 2022, 14(8), 1781; https://doi.org/10.3390/v14081781 - 15 Aug 2022

Cited by 6 | Viewed by 1736

Abstract

Foot-and-mouth disease (FMD) remains one of the major threats to animal health worldwide. Its causative agent, the FMD virus (FMDV), affects cloven-hoofed animals, including farm animals and wildlife species, inflicting severe damage to the international trade and livestock industry. FMDV antigenic variability remains [...] Read more.

Foot-and-mouth disease (FMD) remains one of the major threats to animal health worldwide. Its causative agent, the FMD virus (FMDV), affects cloven-hoofed animals, including farm animals and wildlife species, inflicting severe damage to the international trade and livestock industry. FMDV antigenic variability remains one of the biggest challenges for vaccine-based control strategies. The current study analyzed the host’s adaptive immune responses in cattle immunized with different vaccine protocols and investigated its associations with the clinical outcome after infection with a heterologous strain of FMDV. The results showed that antigenic payload, multivalency, and revaccination may impact on the clinical outcome after heterologous challenge with FMDV. Protection from the experimental infection was related to qualitative traits of the elicited antibodies, such as avidity, IgG isotype composition, and specificity diversity, modulating and reflecting the vaccine-induced maturation of the humoral response. The correlation analyses of the serum avidity obtained per vaccinated individual might suggest that conventional vaccination can induce high-affinity immunoglobulins against conserved epitopes even within different FMDV serotypes. Cross-reaction among strains by these high-affinity antibodies may support further protection against a heterologous infection with FMDV. Full article

(This article belongs to the Special Issue Global Foot-and-Mouth Disease Control)

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6 pages, 1090 KiB

Open AccessCommunication

A Vaccine Based on Asia1 Shamir of the Foot-and-Mouth Disease Virus Offers Low Levels of Protection to Pigs against Asia1/MOG/05, Circulating in East Asia

by Heeyeon Kim, Hwi Won Seo, Ho-Seong Cho and Yeonsu Oh

Viruses 2022, 14(8), 1726; https://doi.org/10.3390/v14081726 - 04 Aug 2022

Cited by 4 | Viewed by 1737

Abstract

Foot-and-mouth disease (FMD) is one of the most contagious diseases in cloven hoof animals. Vaccination can prevent or control FMD, and vaccine antigens should be matched against circulating viruses. According to phylogenetic analyses, field isolates in this region belonged to genotype V and [...] Read more.

Foot-and-mouth disease (FMD) is one of the most contagious diseases in cloven hoof animals. Vaccination can prevent or control FMD, and vaccine antigens should be matched against circulating viruses. According to phylogenetic analyses, field isolates in this region belonged to genotype V and showed low genetic similarity with the Asia1 Shamir vaccine, the OIE-recommended vaccine strain. In this study, we investigated whether pigs vaccinated with the Asia1 Shamir vaccine could be protected from challenges with the Asia1/MOG/05 virus, one of the genotype V field isolates. Eight pigs were divided into either vaccinated or nonvaccinated control groups. After two vaccinations with Asia1 Shamir, both groups of pigs were challenged with the Asia1/MOG/05 field isolate at 2 weeks after the second vaccination. In the control group, symptoms appeared at 2 days post-infection (dpi). The clinical sign score peaked at 4 dpi, and this coincided with virus shedding through nasal discharge. Neutralizing antibody titers peaked at 17 dpi. In the vaccinated group, clinical signs were delayed compared with the control group, and the highest score was shown at 10 dpi accompanied with virus nasal shedding, which peaked at 11 dpi. Neutralizing antibodies were induced 2 weeks after the second vaccination and peaked at 17 dpi. In conclusion, Asia1 Shamir vaccination in pigs provided partial protection from Asia1/MOG/05 virus infection. Full article

(This article belongs to the Special Issue Global Foot-and-Mouth Disease Control)

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17 pages, 2911 KiB

Open AccessArticle

Evolutionary Dynamics of Foot and Mouth Disease Virus Serotype A and Its Endemic Sub-Lineage A/ASIA/Iran-05/SIS-13 in Pakistan

by Syeda Sumera Naqvi, Nazish Bostan, Katsuhiko Fukai, Qurban Ali, Kazuki Morioka, Tatsuya Nishi, Muhammad Abubakar, Zaheer Ahmed, Sadia Sattar, Sundus Javed, Aamira Tariq and Asma Sadiq

Viruses 2022, 14(8), 1634; https://doi.org/10.3390/v14081634 - 26 Jul 2022

Cited by 3 | Viewed by 1891

Abstract

Foot and mouth disease (FMD) causes severe economic losses to the livestock industry of endemic countries, including Pakistan. Pakistan is part of the endemic pool 3 for foot and mouth disease viruses (FMDV), characterized by co-circulating O, A, and Asia 1 serotypes, as [...] Read more.

Foot and mouth disease (FMD) causes severe economic losses to the livestock industry of endemic countries, including Pakistan. Pakistan is part of the endemic pool 3 for foot and mouth disease viruses (FMDV), characterized by co-circulating O, A, and Asia 1 serotypes, as designated by the world reference laboratory for FMD (WRL-FMD). FMDV serotype A lineage ASIA/Iran-05 is widespread in buffalos and cattle populations and was first reported in Pakistan in 2006. This lineage has a high turnover, with as many as 10 sub-lineages reported from Pakistan over the years. In this study, we reconstructed the evolutionary, demographic, and spatial history of serotype A and one of its sub-lineages, A/ASIA/Iran-05/SIS-13, prevalent in Pakistan. We sequenced nearly complete genomes of three isolates belonging to sub-lineage A/ASIA/Iran-05/SIS-13. We estimated recombination patterns and natural selection acting on the serotype A genomes. Source and transmission routes in Pakistan were inferred, and the clustering pattern of isolates of the SIS-13 sub-lineage were mapped on a tree. We hereby report nearly complete genome sequences of isolates belonging to sub-lineage A/ASIA/Iran-05/SIS-13, along with purported recombinant genomes, and highlight that complete coding sequences can better elucidate the endemic history and evolutionary pressures acting on long-term co-circulating FMDV strains. Full article

(This article belongs to the Special Issue Global Foot-and-Mouth Disease Control)

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15 pages, 21754 KiB

Open AccessArticle

Temporal and Spatial Patterns and a Space–Time Cluster Analysis of Foot-and-Mouth Disease Outbreaks in Ethiopia from 2010 to 2019

by Fanos Tadesse Woldemariyam, Samson Leta, Zerihun Assefa, Etsegent Tekeba, Dereje Shegu Gebrewold and Jan Paeshuyse

Viruses 2022, 14(7), 1558; https://doi.org/10.3390/v14071558 - 16 Jul 2022

Cited by 4 | Viewed by 2137

Abstract

Foot-and-mouth disease (FMD) is an endemic disease in Ethiopia, although space–time cluster and monthly variation studies have never been assessed at national level. The current study aimed to identify the spatial and temporal distribution of FMD outbreaks in Ethiopia from national outbreak reports [...] Read more.

Foot-and-mouth disease (FMD) is an endemic disease in Ethiopia, although space–time cluster and monthly variation studies have never been assessed at national level. The current study aimed to identify the spatial and temporal distribution of FMD outbreaks in Ethiopia from national outbreak reports over a period of ten years from 1 January 2010 to 31 December 2019. To this end, a total of 376,762 cases and 1302 outbreaks from 704 districts were obtained from the Minister of Agriculture for analyses. In general, the dry periods, i.e., October to March, of the year were recorded as the peak outbreak periods, with the highest prevalence in March 2012. The monthly average and the outbreak trends over ten years show a decrease of outbreaks from 2010 to 2019. Decomposing the FMD outbreak data time series showed that once an outbreak erupted, it continued for up to five years. Only 12% of the reported outbreaks were assigned to a specific serotype. Within these outbreaks, the serotypes O, A, SAT-2, and SAT-1 were identified in decreasing order of prevalence, respectively. When a window of 50% for the maximum temporal/space cluster size was set, a total of seven FMD clusters were identified in space and time. The primary cluster with a radius of 380.95 km was identified in the southern part of Ethiopia, with a likelihood ratio of 7.67 (observed/expected cases). The third cluster, with a radius of 144.14 km, was identified in the northeastern part of the country, and had a likelihood ratio of 5.66. Clusters 1 and 3 occurred from January 2017 to December 2019. The second cluster that occurred had a radius of 294.82 km, a likelihood ratio of 6.20, and was located in the central and western parts of Ethiopia. The sixth cluster, with a radius of 36.04 km and a likelihood ratio of 20.60, was set in southern Tigray, bordering Afar. Clusters 2 and 6 occurred in the same period, from January 2014 to December 2016. The fourth cluster in northern Tigray had a calculated radius of 95.50 km and a likelihood ratio of 1.17. The seventh cluster occurred in the north-central Amhara region, with a radius of 97 km and a likelihood ratio of 1.16. Clusters 4 and 7 occurred between January 2010 and December 2013. The spatiotemporal and cluster analysis of the FMD outbreaks identified in the context of the current study are crucial in implementing control, prevention, and a prophylactic vaccination schedule. This study pointed out October to March as well as the main time of the year during which FMD outbreaks occur. The area that extends from the south to north, following the central highlands, is the main FMD outbreak area in Ethiopia. Full article

(This article belongs to the Special Issue Global Foot-and-Mouth Disease Control)

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18 pages, 3046 KiB

Open AccessArticle

Cross-Serotype Reactivity of ELISAs Used to Detect Antibodies to the Structural Proteins of Foot-and-Mouth Disease Virus

by Anna B. Ludi, Alison Morris, Simon Gubbins, Amin Asfor, Madeeha Afzal, Clare F. Browning, Santina Grazioli, Efrem Alessandro Foglia, Ginette Wilsden, Alison Burman, Emiliana Brocchi, David J. Paton and Donald P. King

Viruses 2022, 14(7), 1495; https://doi.org/10.3390/v14071495 - 08 Jul 2022

Cited by 8 | Viewed by 2146

Abstract

Antibodies to the foot-and-mouth disease virus (FMDV) capsid induced by infection or vaccination can provide serotype-specific protection and be measured using virus neutralization tests and viral structural-protein (SP-)ELISAs. Separate tests are needed for each serotype, but cross-serotype reactions complicate serotyping. In this study, [...] Read more.

Antibodies to the foot-and-mouth disease virus (FMDV) capsid induced by infection or vaccination can provide serotype-specific protection and be measured using virus neutralization tests and viral structural-protein (SP-)ELISAs. Separate tests are needed for each serotype, but cross-serotype reactions complicate serotyping. In this study, inter-serotypic responses were quantified for five SP-ELISA formats by testing 294 monovalent mainly bovine sera collected following infection, vaccination, or vaccination and infection with one of five serotypes of FMDV. Over half of the samples, representing all three immunization categories, scored positive for at least one heterologous serotype and some scored positive for all serotypes tested. A comparative approach to identifying the strongest reaction amongst serotypes O, A and Asia 1 improved the accuracy of serotyping to 73–100% depending on the serotype and test system, but this method will be undermined where animals have been infected and/or vaccinated with multiple FMDV serotypes. Preliminary studies with stabilized recombinant capsid antigens of serotypes O and A that do not expose internal epitopes showed reduced cross-reactivity, supporting the hypothesis that capsid integrity can affect the serotype-specificity of the SP-ELISAs. The residual cross-reactivity associated with capsid surface epitopes was consistent with the evidence of cross-serotype virus neutralization. Full article

(This article belongs to the Special Issue Global Foot-and-Mouth Disease Control)

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14 pages, 1045 KiB

Open AccessArticle

Time-Series Analysis for the Number of Foot and Mouth Disease Outbreak Episodes in Cattle Farms in Thailand Using Data from 2010–2020

by Veerasak Punyapornwithaya, Pradeep Mishra, Chalutwan Sansamur, Dirk Pfeiffer, Orapun Arjkumpa, Rotchana Prakotcheo, Thanis Damrongwatanapokin and Katechan Jampachaisri

Viruses 2022, 14(7), 1367; https://doi.org/10.3390/v14071367 - 23 Jun 2022

Cited by 10 | Viewed by 2940

Abstract

Thailand is one of the countries where foot and mouth disease outbreaks have resulted in considerable economic losses. Forecasting is an important warning technique that can allow authorities to establish an FMD surveillance and control program. This study aimed to model and forecast [...] Read more.

Thailand is one of the countries where foot and mouth disease outbreaks have resulted in considerable economic losses. Forecasting is an important warning technique that can allow authorities to establish an FMD surveillance and control program. This study aimed to model and forecast the monthly number of FMD outbreak episodes (n-FMD episodes) in Thailand using the time-series methods, including seasonal autoregressive integrated moving average (SARIMA), error trend seasonality (ETS), neural network autoregression (NNAR), and Trigonometric Exponential smoothing state–space model with Box–Cox transformation, ARMA errors, Trend and Seasonal components (TBATS), and hybrid methods. These methods were applied to monthly n-FMD episodes (n = 1209) from January 2010 to December 2020. Results showed that the n-FMD episodes had a stable trend from 2010 to 2020, but they appeared to increase from 2014 to 2020. The outbreak episodes followed a seasonal pattern, with a predominant peak occurring from September to November annually. The single-technique methods yielded the best-fitting time-series models, including

S A R I M A (1, 0, 1) {(0, 1, 1)}_{12}

,

N N A R {(3, 1, 2)}_{12}

,

E T S (A, N, A)

, and

T B A T S (1, {0, 0}, 0.8, {< 12, 5 >}

. Moreover, SARIMA-NNAR and NNAR-TBATS were the hybrid models that performed the best on the validation datasets. The models that incorporate seasonality and a non-linear trend performed better than others. The forecasts highlighted the rising trend of n-FMD episodes in Thailand, which shares borders with several FMD endemic countries in which cross-border trading of cattle is found common. Thus, control strategies and effective measures to prevent FMD outbreaks should be strengthened not only in Thailand but also in neighboring countries. Full article

(This article belongs to the Special Issue Global Foot-and-Mouth Disease Control)

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10 pages, 2860 KiB

Open AccessCommunication

Trans-Encapsidation of Foot-and-Mouth Disease Virus Genomes Facilitates Escape from Neutralizing Antibodies

by Kay Childs, Ben Jackson, Yongjie Harvey and Julian Seago

Viruses 2022, 14(6), 1161; https://doi.org/10.3390/v14061161 - 27 May 2022

Cited by 4 | Viewed by 1857

Abstract

Foot-and-mouth disease is an economically devastating disease of livestock caused by foot-and-mouth disease virus (FMDV). Vaccination is the most effective control measure in place to limit the spread of the disease; however, the success of vaccination campaigns is hampered by the antigenic diversity [...] Read more.

Foot-and-mouth disease is an economically devastating disease of livestock caused by foot-and-mouth disease virus (FMDV). Vaccination is the most effective control measure in place to limit the spread of the disease; however, the success of vaccination campaigns is hampered by the antigenic diversity of FMDV and the rapid rate at which new strains emerge that escape pre-existing immunity. FMDV has seven distinct serotypes, and within each serotype are multiple strains that often induce little cross-protective immunity. The diversity of FMDV is a consequence of the high error rate of the RNA-dependent RNA polymerase, accompanied by extensive recombination between genomes during co-infection. Since multiple serotypes and strains co-circulate in regions where FMDV is endemic, co-infection is common, providing the conditions for recombination, and also for other events such as trans-encapsidation in which the genome of one virus is packaged into the capsid of the co-infecting virus. Here, we demonstrate that the co-infection of cells with two FMDVs of different serotypes results in trans-encapsidation of both viral genomes. Crucially, this facilitates the infection of new cells in the presence of neutralizing antibodies that recognize the capsid that is encoded by the packaged genome. Full article

(This article belongs to the Special Issue Global Foot-and-Mouth Disease Control)

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15 pages, 7965 KiB

Open AccessArticle

Outbreaks of Foot-and-Mouth Disease in Burundi, East Africa, in 2016, Caused by Different Serotypes

by Andrea Isabel Estevez Garcia, David J. Lefebvre, Lionel Nyabongo, Andy Haegeman, Canesius Nkundwanayo, Annebel De Vleeschauwer, Désiré Ntakirutimana, Ilse De Leeuw, Deogratias Nsanganiyumwami, Pascal Niyokwizera, Thierry van den Berg, Alfred Niyokwishimira and Kris De Clercq

Viruses 2022, 14(5), 1077; https://doi.org/10.3390/v14051077 - 17 May 2022

Cited by 2 | Viewed by 2158

Abstract

Burundi is a small, densely populated country in the African Great Lakes region. In March 2016, several hundreds of cattle were reported with vesicular lesions, suggesting foot-and-mouth disease (FMD). Epithelial samples, saliva, and blood were collected in six of the affected provinces spread [...] Read more.

Burundi is a small, densely populated country in the African Great Lakes region. In March 2016, several hundreds of cattle were reported with vesicular lesions, suggesting foot-and-mouth disease (FMD). Epithelial samples, saliva, and blood were collected in six of the affected provinces spread over the country. The overall seroprevalence of FMD virus (FMDV) in the affected herds, as determined by antibodies against FMDV non-structural proteins, was estimated at 87%. Antibodies against FMDV serotypes O (52%), A (44%), C (19%), SAT1 (36%), SAT2 (58%), and SAT3 (23%) were detected across the provinces. FMDV genome was detected in samples from five of the six provinces using rRT-PCR. FMDV was isolated from samples from three provinces: in Cibitoke province, serotypes A and SAT2 were isolated, while in Mwaro and Rutana provinces, only serotype SAT2 was isolated. In Bururi and Cankuzo provinces, the serological profile suggested a recent incursion with serotype SAT2, while in Bubanza province, the serological profile suggested past incursions with serotype O and possibly serotype SAT1. The phylogenetic assessments showed the presence of topotypes A/Africa/G-I and SAT2/IV, similarly to previously characterized virus strains from other countries in the region, suggesting a transboundary origin and necessitating a regional approach for vaccination and control of FMD. Full article

(This article belongs to the Special Issue Global Foot-and-Mouth Disease Control)

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11 pages, 1421 KiB

Open AccessArticle

Transiently Transfected Mammalian Cell Cultures: An Adaptable and Effective Platform for Virus-like Particle-Based Vaccines against Foot-and-Mouth Disease Virus

by Michael Puckette, Victoria Primavera, Erica Martel, Jose Barrera, William Hurtle, Benjamin Clark, Barbara Kamicker, Mariceny Zurita, David Brake and John Neilan

Viruses 2022, 14(5), 989; https://doi.org/10.3390/v14050989 - 07 May 2022

Cited by 6 | Viewed by 2319

Abstract

RNA viruses, such as foot-and-mouth disease virus (FMDV), have error-prone replication resulting in the continuous emergence of new viral strains capable of evading current vaccine coverage. Vaccine formulations must be regularly updated, which is both costly and technically challenging for many vaccine platforms. [...] Read more.

RNA viruses, such as foot-and-mouth disease virus (FMDV), have error-prone replication resulting in the continuous emergence of new viral strains capable of evading current vaccine coverage. Vaccine formulations must be regularly updated, which is both costly and technically challenging for many vaccine platforms. In this report, we describe a plasmid-based virus-like particle (VLP) production platform utilizing transiently transfected mammalian cell cultures that combines both the rapid response adaptability of nucleic-acid-based vaccines with the ability to produce intact capsid epitopes required for immunity. Formulated vaccines which employed this platform conferred complete protection from clinical foot-and-mouth disease in both swine and cattle. This novel platform can be quickly adapted to new viral strains and serotypes through targeted exchanges of only the FMDV capsid polypeptide nucleic acid sequences, from which processed structural capsid proteins are derived. This platform obviates the need for high biocontainment manufacturing facilities to produce inactivated whole-virus vaccines from infected mammalian cell cultures, which requires upstream expansion and downstream concentration of large quantities of live virulent viruses. Full article

(This article belongs to the Special Issue Global Foot-and-Mouth Disease Control)

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16 pages, 1728 KiB

Open AccessArticle

Viral Population Diversity during Co-Infection of Foot-And-Mouth Disease Virus Serotypes SAT1 and SAT2 in African Buffalo in Kenya

by Rachel M. Palinski, Barbara Brito, Frederick R. Jaya, Abraham Sangula, Francis Gakuya, Miranda R. Bertram, Steven J. Pauszek, Ethan J. Hartwig, George R. Smoliga, Vincent Obanda, George P. Omondi, Kimberly VanderWaal and Jonathan Arzt

Viruses 2022, 14(5), 897; https://doi.org/10.3390/v14050897 - 25 Apr 2022

Cited by 4 | Viewed by 2692

Abstract

African buffalo are the natural reservoirs of the SAT serotypes of foot-and-mouth disease virus (FMDV) in sub-Saharan Africa. Most buffalo are exposed to multiple FMDV serotypes early in life, and a proportion of them become persistently infected carriers. Understanding the genetic diversity and [...] Read more.

African buffalo are the natural reservoirs of the SAT serotypes of foot-and-mouth disease virus (FMDV) in sub-Saharan Africa. Most buffalo are exposed to multiple FMDV serotypes early in life, and a proportion of them become persistently infected carriers. Understanding the genetic diversity and evolution of FMDV in carrier animals is critical to elucidate how FMDV persists in buffalo populations. In this study, we obtained oropharyngeal (OPF) fluid from naturally infected African buffalo, and characterized the genetic diversity of FMDV. Out of 54 FMDV-positive OPF, 5 were co-infected with SAT1 and SAT2 serotypes. From the five co-infected buffalo, we obtained eighty-nine plaque-purified isolates. Isolates obtained directly from OPF and plaque purification were sequenced using next-generation sequencing (NGS). Phylogenetic analyses of the sequences obtained from recombination-free protein-coding regions revealed a discrepancy in the topology of capsid proteins and non-structural proteins. Despite the high divergence in the capsid phylogeny between SAT1 and SAT2 serotypes, viruses from different serotypes that were collected from the same host had a high genetic similarity in non-structural protein-coding regions P2 and P3, suggesting interserotypic recombination. In two of the SAT1 and SAT2 co-infected buffalo identified at the first passage of viral isolation, the plaque-derived SAT2 genomes were distinctly grouped in two different genotypes. These genotypes were not initially detected with the NGS from the first passage (non-purified) virus isolation sample. In one animal with two SAT2 haplotypes, one plaque-derived chimeric sequence was found. These findings demonstrate within-host evolution through recombination and point mutation contributing to broad viral diversity in the wildlife reservoir. These mechanisms may be critical to FMDV persistence at the individual animal and population levels, and may contribute to the emergence of new viruses that have the ability to spill-over to livestock and other wildlife species. Full article

(This article belongs to the Special Issue Global Foot-and-Mouth Disease Control)

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17 pages, 683 KiB

Open AccessArticle

Development and Evaluation of Molecular Pen-Side Assays without Prior RNA Extraction for Peste des Petits Ruminants (PPR) and Foot and Mouth Disease (FMD)

by David Edge, Mana Mahapatra, Shona Strachan, James Turton, Ryan Waters, Camilla Benfield, Nathan Nazareth, Felix Njeumi, Nelson Nazareth and Satya Parida

Viruses 2022, 14(4), 835; https://doi.org/10.3390/v14040835 - 17 Apr 2022

Viewed by 2326

Abstract

Animal diseases such as peste des petits ruminants (PPR) and foot and mouth disease (FMD) cause significant economic losses in endemic countries and fast, accurate in-field diagnostics would assist with surveillance and outbreak control. The detection of these pathogens is usually performed at [...] Read more.

Animal diseases such as peste des petits ruminants (PPR) and foot and mouth disease (FMD) cause significant economic losses in endemic countries and fast, accurate in-field diagnostics would assist with surveillance and outbreak control. The detection of these pathogens is usually performed at reference laboratories, tested using assays that are recommended by The World Organisation for Animal Health (OIE), leading to delays in pathogen detection. This study seeks to demonstrate a proof-of-concept approach for a molecular diagnostic assay that is compatible with material direct from nasal swab sampling, without the need for a prior nucleic acid extraction step, that could potentially be applied at pen-side for both PPR and FMD. The use of such a rapid, low-cost assay without the need for a cold chain could permit testing capacity to be established in remote, resource limited areas and support the surveillance activities necessary to meet the goal of eradication of PPR by 2030. Two individual assays were developed that detect > 99% of PPR and FMD sequences available in GenBank, demonstrating pan-serotype FMD and pan-lineage PPR assays. The ability for the BioGene XF reagent that was used in this study to lyse FMD and PPR viruses and amplify their nucleic acids in the presence of unprocessed nasal swab eluate was evaluated. The reagent was shown to be capable of detecting the viral RNA present in nasal swabs collected from naïve and infected target animals. A study was performed comparing the relative specificity and sensitivity of the new assays to the reference assays. The study used nasal swabs collected from animals before and after infection (12 cattle infected with FMDV and 5 goats infected with PPRV) and both PPR and FMD viral RNA were successfully detected two to four days post-infection in all animals using either the XF or reference assay reagents. These data suggest that the assays are at least as sensitive as the reference assays and support the need for further studies in a field setting. Full article

(This article belongs to the Special Issue Global Foot-and-Mouth Disease Control)

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8 pages, 681 KiB

Open AccessArticle

Combining a Universal Capture Ligand and Pan-Serotype Monoclonal Antibody to Develop a Pan-Serotype Lateral Flow Strip Test for Foot-and-Mouth Disease Virus Detection

by Ming Yang, Dmytro Zhmendak, Valerie Mioulet, Donald P. King, Alison Burman and Charles K. Nfon

Viruses 2022, 14(4), 785; https://doi.org/10.3390/v14040785 - 10 Apr 2022

Cited by 5 | Viewed by 2430

Abstract

Foot-and-mouth disease virus (FMDV) causes FMD, a highly contagious disease of cloven-hoofed animals including cattle, goats, pigs and sheep. Rapid detection of FMDV is critical to limit the devastating economic losses due to FMD. Current laboratory methods for FMDV detection such as virus [...] Read more.

Foot-and-mouth disease virus (FMDV) causes FMD, a highly contagious disease of cloven-hoofed animals including cattle, goats, pigs and sheep. Rapid detection of FMDV is critical to limit the devastating economic losses due to FMD. Current laboratory methods for FMDV detection such as virus isolation, real-time reverse transcription PCR and antigen detection enzyme-linked immunosorbent assay (AgELISA) are labor-intensive, requiring trained personnel and specialized equipment. We present the development and validation of a pan-serotype lateral flow strip test (LFST) that uses recombinant bovine integrin αvβ6 as a universal capture ligand and a pan-serotype monoclonal antibody (mAb) to detect FMDV. The LFST detected all seven FMDV serotypes, where the diagnostic sensitivity was comparable to the AgELISA, and the diagnostic specificity was 100% without cross-reactivity to other viruses causing vesicular disease in livestock. This rapid test will be useful for on-site FMDV detection, as well as in laboratories in endemic countries where laboratory resources are limited. Full article

(This article belongs to the Special Issue Global Foot-and-Mouth Disease Control)

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13 pages, 2309 KiB

Open AccessArticle

Avidity of Polyclonal Antibodies to Foot-and-Mouth Disease Virus in Bovine Serum Measured Using Bio-Layer Interferometry

by Andrew E. Shaw, Alison Burman, Amin Asfor, Emiliana Brocchi, Santina Grazioli, Clare Browning, Anna Ludi, Tobias J. Tuthill and Donald P. King

Viruses 2022, 14(4), 714; https://doi.org/10.3390/v14040714 - 29 Mar 2022

Cited by 2 | Viewed by 2633

Abstract

Foot-and-mouth disease (FMD) is a disease of cloven-hoofed livestock caused by FMD virus (FMDV). FMD can be controlled through the use of inactivated vaccines, and it is well established that the protection afforded by FMD vaccines correlates strongly with neutralising antibody titres. However, [...] Read more.

Foot-and-mouth disease (FMD) is a disease of cloven-hoofed livestock caused by FMD virus (FMDV). FMD can be controlled through the use of inactivated vaccines, and it is well established that the protection afforded by FMD vaccines correlates strongly with neutralising antibody titres. However, the overall strength of binding, referred to as avidity, is also an important parameter with respect to the ability of antibodies to neutralise virus infection, and there is evidence that avidity can affect the level of protection afforded by FMDV vaccines. Here, as an alternative to modified enzyme-linked immunosorbent assays (avidity ELISAs) incorporating a chaotropic wash step, we used bio-layer interferometry (BLI) to measure the avidity of bovine polyclonal antibodies against FMDV capsids. We conducted preliminary experiments using recombinant FMDV capsids, as well as peptides representing antigenic loops, to demonstrate that the binding of monoclonal antibodies targeting specific antigenic sites could be detected using BLI. Subsequent experiments using polyclonal sera derived from FMD vaccinated cattle provided evidence of a positive correlation between the neutralising titre of the serum and the avidity as measured by BLI. Furthermore, we observed an increase in BLI avidity, as well as in the titre, in vaccinated animals upon challenge with the live virus. Full article

(This article belongs to the Special Issue Global Foot-and-Mouth Disease Control)

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24 pages, 2868 KiB

Open AccessArticle

Assessment of the Risk of Foot and Mouth Disease among Beef Cattle at Slaughter from East African Production Systems

by Julie Adamchick, Karl M. Rich and Andres M. Perez

Viruses 2021, 13(12), 2407; https://doi.org/10.3390/v13122407 - 01 Dec 2021

Cited by 2 | Viewed by 2190

Abstract

Endemic foot and mouth disease (FMD) in East African cattle systems is one factor that limits access to export markets. The probability of FMD transmission associated with export from such systems have never been quantified and there is a need for data and [...] Read more.

Endemic foot and mouth disease (FMD) in East African cattle systems is one factor that limits access to export markets. The probability of FMD transmission associated with export from such systems have never been quantified and there is a need for data and analyses to guide strategies for livestock exports from regions where FMD remains endemic. The probability of infection among animals at slaughter is an important contributor to the risk of FMD transmission associated with the final beef product. In this study, we built a stochastic model to estimate the probability that beef cattle reach slaughter while infected with FMD virus for four production systems in two East African countries (Kenya and Uganda). Input values were derived from the primary literature and expert opinion. We found that the risk that FMD-infected animals reach slaughter under current conditions is high in both countries (median annual probability ranging from 0.05 among cattle from Kenyan feedlots to 0.62 from Ugandan semi-intensive systems). Cattle originating from feedlot and ranching systems in Kenya had the lowest overall probabilities of the eight systems evaluated. The final probabilities among cattle from all systems were sensitive to the likelihood of acquiring new infections en route to slaughter and especially the probability and extent of commingling with other cattle. These results give insight into factors that could be leveraged by potential interventions to lower the probability of FMD among beef cattle at slaughter. Such interventions should be evaluated considering the cost, logistics, and tradeoffs of each, ultimately guiding resource investment that is grounded in the values and capacity of each country. Full article

(This article belongs to the Special Issue Global Foot-and-Mouth Disease Control)

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19 pages, 3833 KiB

Open AccessArticle

Interleukin-10-Mediated Lymphopenia Caused by Acute Infection with Foot-and-Mouth Disease Virus in Mice

by Zijing Guo, Yin Zhao, Zhidong Zhang and Yanmin Li

Viruses 2021, 13(12), 2358; https://doi.org/10.3390/v13122358 - 24 Nov 2021

Cited by 5 | Viewed by 2424

Abstract

Foot-and-mouth disease (FMD) is characterized by a pronounced lymphopenia that is associated with immune suppression. However, the mechanisms leading to lymphopenia remain unclear. In this study, the number of total CD4⁺, CD8⁺ T cells, B cells, and NK cells in [...] Read more.

Foot-and-mouth disease (FMD) is characterized by a pronounced lymphopenia that is associated with immune suppression. However, the mechanisms leading to lymphopenia remain unclear. In this study, the number of total CD4⁺, CD8⁺ T cells, B cells, and NK cells in the peripheral blood were dramatically reduced in C57BL/6 mice infected with foot-and-mouth disease virus (FMDV) serotype O, and it was noted that mice with severe clinical symptoms had expressively lower lymphocyte counts than mice with mild or without clinical symptoms, indicating that lymphopenia was associated with disease severity. A further analysis revealed that lymphocyte apoptosis and trafficking occurred after FMDV infection. In addition, coinhibitory molecules were upregulated in the expression of CD4⁺ and CD8⁺ T cells from FMDV-infected mice, including CTLA-4, LAG-3, 2B4, and TIGIT. Interestingly, the elevated IL-10 in the serum was correlated with the appearance of lymphopenia during FMDV infection but not IL-6, IL-2, IL-17, IL-18, IL-1β, TNF-α, IFN-α/β, TGF-β, and CXCL1. Knocking out IL-10 (IL-10^-/-) mice or blocking IL-10/IL-10R signaling in vivo was able to prevent lymphopenia via downregulating apoptosis, trafficking, and the coinhibitory expression of lymphocytes in the peripheral blood, which contribute to enhance the survival of mice infected with FMDV. Our findings support that blocking IL-10/IL-10R signaling may represent a novel therapeutic approach for FMD. Full article

(This article belongs to the Special Issue Global Foot-and-Mouth Disease Control)

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16 pages, 1480 KiB

Open AccessArticle

Use of Slaughterhouses as Sentinel Points for Genomic Surveillance of Foot-and-Mouth Disease Virus in Southern Vietnam

by Umanga Gunasekara, Miranda R. Bertram, Do H. Dung, Bui H. Hoang, Nguyen T. Phuong, Vo V. Hung, Nguyen V. Long, Phan Q. Minh, Le T. Vu, Pham V. Dong, Andres Perez, Kimberly VanderWaal and Jonathan Arzt

Viruses 2021, 13(11), 2203; https://doi.org/10.3390/v13112203 - 02 Nov 2021

Cited by 4 | Viewed by 2123

Abstract

The genetic diversity of foot-and-mouth disease virus (FMDV) poses a challenge to the successful control of the disease, and it is important to identify the emergence of different strains in endemic settings. The objective of this study was to evaluate the sampling of [...] Read more.

The genetic diversity of foot-and-mouth disease virus (FMDV) poses a challenge to the successful control of the disease, and it is important to identify the emergence of different strains in endemic settings. The objective of this study was to evaluate the sampling of clinically healthy livestock at slaughterhouses as a strategy for genomic FMDV surveillance. Serum samples (n = 11,875) and oropharyngeal fluid (OPF) samples (n = 5045) were collected from clinically healthy cattle and buffalo on farms in eight provinces in southern and northern Vietnam (2015–2019) to characterize viral diversity. Outbreak sequences were collected between 2009 and 2019. In two slaughterhouses in southern Vietnam, 1200 serum and OPF samples were collected from clinically healthy cattle and buffalo (2017 to 2019) as a pilot study on the use of slaughterhouses as sentinel points in surveillance. FMDV VP1 sequences were analyzed using discriminant principal component analysis and time-scaled phylodynamic trees. Six of seven serotype-O and -A clusters circulating in southern Vietnam between 2017–2019 were detected at least once in slaughterhouses, sometimes pre-dating outbreak sequences associated with the same cluster by 4–6 months. Routine sampling at slaughterhouses may provide a timely and efficient strategy for genomic surveillance to identify circulating and emerging FMDV strains. Full article

(This article belongs to the Special Issue Global Foot-and-Mouth Disease Control)

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14 pages, 2310 KiB

Open AccessArticle

Characterization of Foot-and-Mouth Disease Viruses in Zambia-Implications for the Epidemiology of the Disease in Southern Africa

by Frank Banda, Yona Sinkala, Liywalli Mataa, Phiyani Lebea, Tingiya Sikombe, Henry L. Kangwa, Elliot M. Fana, Mokganedi Mokopasetso, Jemma Wadsworth, Nick J. Knowles, Donald P. King and Melvyn Quan

Viruses 2021, 13(11), 2195; https://doi.org/10.3390/v13112195 - 31 Oct 2021

Cited by 2 | Viewed by 3247

Abstract

The livestock industry supports livelihood and nutritional security of at least 42% of people in the Southern African Development Community region. However, presence of animal diseases such as foot-and-mouth disease poses a major threat to the development of this industry. Samples collected from [...] Read more.

The livestock industry supports livelihood and nutritional security of at least 42% of people in the Southern African Development Community region. However, presence of animal diseases such as foot-and-mouth disease poses a major threat to the development of this industry. Samples collected from FMD outbreaks in Zambia during 2015–2020, comprising epithelial tissues samples (n = 47) and sera (n = 120), were analysed. FMD virus was serotyped in 26 samples, while 92 sera samples tested positive on NSP-ELISA. Phylogenetic analysis revealed notable changes in the epidemiology of FMD in Zambia, which included: (i) introduction of a novel FMDV SAT-3 (topotype II) causing FMD cases in cattle in Western Province; (ii) emergence of FMDV serotype O (topotype O/EA-2) in Central, Southern, Copperbelt, Western, Lusaka Provinces; and (iii) new outbreaks due to SAT -2 (topotypes I) in Eastern Zambia. Together, these data describe eight different epizootics that occurred in Zambia, four of which were outside the known FMD high-risk areas. This study highlights the complex epidemiology of FMD in Zambia, where the country represents an interface between East Africa (Pool 4) and Southern Africa (Pool 6). These changing viral dynamics have direct impacts on FMD vaccine selection in the SADC region. Full article

(This article belongs to the Special Issue Global Foot-and-Mouth Disease Control)

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21 pages, 4589 KiB

Open AccessArticle

Self-Reporting of Risk Pathways and Parameter Values for Foot-and-Mouth Disease in Slaughter Cattle from Alternative Production Systems by Kenyan and Ugandan Veterinarians

by Julie Adamchick, Karl M. Rich and Andres M. Perez

Viruses 2021, 13(11), 2112; https://doi.org/10.3390/v13112112 - 20 Oct 2021

Cited by 5 | Viewed by 1884

Abstract

Countries in which foot-and-mouth disease (FMD) is endemic may face bans on the export of FMD-susceptible livestock and products because of the associated risk for transmission of FMD virus. Risk assessment is an essential tool for demonstrating the fitness of one’s goods for [...] Read more.

Countries in which foot-and-mouth disease (FMD) is endemic may face bans on the export of FMD-susceptible livestock and products because of the associated risk for transmission of FMD virus. Risk assessment is an essential tool for demonstrating the fitness of one’s goods for the international marketplace and for improving animal health. However, it is difficult to obtain the necessary data for such risk assessments in many countries where FMD is present. This study bridged the gaps of traditional participatory and expert elicitation approaches by partnering with veterinarians from the National Veterinary Services of Kenya (n = 13) and Uganda (n = 10) enrolled in an extended capacity-building program to systematically collect rich, local knowledge in a format appropriate for formal quantitative analysis. Participants mapped risk pathways and quantified variables that determine the risk of infection among cattle at slaughter originating from each of four beef production systems in each country. Findings highlighted that risk processes differ between management systems, that disease and sale are not always independent events, and that events on the risk pathway are influenced by the actions and motivations of value chain actors. The results provide necessary information for evaluating the risk of FMD among cattle pre-harvest in Kenya and Uganda and provide a framework for similar evaluation in other endemic settings. Full article

(This article belongs to the Special Issue Global Foot-and-Mouth Disease Control)

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13 pages, 1275 KiB

Open AccessArticle

Molecular Basis of Antigenic Drift in Serotype O Foot-and-Mouth Disease Viruses (2013–2018) from Southeast Asia

by Sasmita Upadhyaya, Mana Mahapatra, Valerie Mioulet and Satya Parida

Viruses 2021, 13(9), 1886; https://doi.org/10.3390/v13091886 - 21 Sep 2021

Cited by 7 | Viewed by 2667

Abstract

Foot and mouth disease (FMD) is a highly contagious disease of cloven-hoofed animals with serious economic consequences. FMD is endemic in Southeast Asia (SEA) and East Asia (EA) with the circulation of multiple serotypes, posing a threat to Australia and other FMD-free countries. [...] Read more.

Foot and mouth disease (FMD) is a highly contagious disease of cloven-hoofed animals with serious economic consequences. FMD is endemic in Southeast Asia (SEA) and East Asia (EA) with the circulation of multiple serotypes, posing a threat to Australia and other FMD-free countries. Although vaccination is one of the most important control measures to prevent FMD outbreaks, the available vaccines may not be able to provide enough cross-protection against the FMD viruses (FMDVs) circulating in these countries due to the incursion of new lineages and sub-lineages as experienced in South Korea during 2010, a FMD-free country, when a new lineage of serotype O FMDV (Mya-98) spread to the country, resulting in devastating economic consequences. In this study, a total of 62 serotype O (2013–2018) viruses selected from SEA and EA countries were antigenically characterized by virus neutralization tests using three existing (O/HKN/6/83, O/IND/R2/75 and O/PanAsia-2) and one putative (O/MYA/2009) vaccine strains and full capsid sequencing. The Capsid sequence analysis revealed three topotypes, Cathay, SEA and Middle East-South Asia (ME-SA) of FMDVs circulating in the region. The vaccines used in this study showed a good match with the SEA and ME-SA viruses. However, none of the recently circulating Cathay topotype viruses were protected by any of the vaccine strains, including the existing Cathay topotype vaccine (O/HKN/6/83), indicating an antigenic drift and, also the urgency to monitor this topotype in the region and develop a new vaccine strain if necessary, although currently the presence of this topotype is mainly restricted to China, Hong Kong, Taiwan and Vietnam. Further, the capsid sequences of these viruses were analyzed that identified several capsid amino acid substitutions involving neutralizing antigenic sites 1, 2 and 5, which either individually or together could underpin the observed antigenic drift. Full article

(This article belongs to the Special Issue Global Foot-and-Mouth Disease Control)

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10 pages, 608 KiB

Open AccessCommunication

Combining Multiple Assays Improves Detection and Serotyping of Foot-and-Mouth Disease Virus. A Practical Example with Field Samples from East Africa

by Efrem Alessandro Foglia, Tiziana Lembo, Rudovick Kazwala, Divine Ekwem, Gabriel Shirima, Santina Grazioli, Emiliana Brocchi and Giulia Pezzoni

Viruses 2021, 13(8), 1583; https://doi.org/10.3390/v13081583 - 10 Aug 2021

Cited by 6 | Viewed by 2817

Abstract

Multiple serotypes and topotypes of foot-and-mouth disease virus (FMDV) circulate in endemic areas, posing considerable impacts locally. In addition, introductions into new areas are of great concern. Indeed, in recent years, multiple FMDV outbreaks, caused by topotypes that have escaped from their original [...] Read more.

Multiple serotypes and topotypes of foot-and-mouth disease virus (FMDV) circulate in endemic areas, posing considerable impacts locally. In addition, introductions into new areas are of great concern. Indeed, in recent years, multiple FMDV outbreaks, caused by topotypes that have escaped from their original areas, have been recorded in various parts of the world. In both cases, rapid and accurate diagnosis, including the identification of the serotype and topotype causing the given outbreaks, plays an important role in the implementation of the most effective and appropriate measures to control the spread of the disease. In the present study, we describe the performance of a range of diagnostic and typing tools for FMDV on a panel of vesicular samples collected in northern Tanzania (East Africa, EA) during 2012–2018. Specifically, we tested these samples with a real-time RT-PCR targeting 3D sequence for pan-FMDV detection; an FMDV monoclonal antibody-based antigen (Ag) detection and serotyping ELISA kit; virus isolation (VI) on LFBKαVβ6 cell line; and a panel of four topotype-specific real-time RT-PCRs, specifically tailored for circulating strains in EA. The 3D real-time RT-PCR showed the highest diagnostic sensitivity, but it lacked typing capacity. Ag-ELISA detected and typed FMDV in 71% of sample homogenates, while VI combined with Ag-ELISA for typing showed an efficiency of 82%. The panel of topotype-specific real-time RT-PCRs identified and typed FMDV in 93% of samples. However, the SAT1 real-time RT-PCR had the highest (20%) failure rate. Briefly, topotype-specific real-time RT-PCRs had the highest serotyping capacity for EA FMDVs, although four assays were required, while the Ag-ELISA, which was less sensitive, was the most user-friendly, hence suitable for any laboratory level. In conclusion, when the four compared tests were used in combination, both the diagnostic and serotyping performances approached 100%. Full article

(This article belongs to the Special Issue Global Foot-and-Mouth Disease Control)

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19 pages, 1147 KiB

Open AccessArticle

Development and Validation of Confirmatory Foot-and-Mouth Disease Virus Antibody ELISAs to Identify Infected Animals in Vaccinated Populations

by Anuj Tewari, Helen Ambrose, Krupali Parekh, Toru Inoue, Javier Guitian, Antonello Di Nardo, David James Paton and Satya Parida

Viruses 2021, 13(5), 914; https://doi.org/10.3390/v13050914 - 15 May 2021

Cited by 6 | Viewed by 3113

Abstract

In foot-and-mouth disease (FMD)-endemic countries, vaccination is commonly used to control the disease, whilst in FMD-free countries, vaccination is considered as an option, in addition to culling the infected and in contact animals. FMD vaccines are mainly comprised of inactivated virions and stimulate [...] Read more.

In foot-and-mouth disease (FMD)-endemic countries, vaccination is commonly used to control the disease, whilst in FMD-free countries, vaccination is considered as an option, in addition to culling the infected and in contact animals. FMD vaccines are mainly comprised of inactivated virions and stimulate protective antibodies to virus structural proteins. In contrast, infection with FMD virus leads to virus replication and additional antibody responses to viral nonstructural proteins (NSP). Therefore, antibodies against NSPs are used to differentiate infection in vaccinated animals (DIVA), in order to estimate the prevalence of infection or its absence. Another advantage of NSP antibody tests is that they detect FMD infection in the field, irrespective of the serotypes of virus in circulation. In cattle, the NSP tests that target the 3ABC polyprotein provides the highest sensitivity, detecting up to 90% of vaccinated animals that become carriers after exposure to infection, with a specificity of around 99%. Due to insufficient diagnostic sensitivity and specificity, detection of a low level of infection is difficult at the population level with a high degree of confidence. The low level of non-specific responses can be overcome by retesting samples scored positive using a second confirmatory test, which should have at least comparable sensitivity to the first test. In this study, six in-house tests were developed incorporating different NSP antigens, and validated using bovine sera from naïve animals, field cases and experimentally vaccinated and/or infected animals. In addition, two (short and long incubation) new commercial NSP tests based on 3ABC competitive blocking ELISAs (ID Screen^® FMD NSP Competition, IDvet, France) were validated in this study. The two commercial ELISAs had very similar sensitivities and specificities that were not improved by lengthening the incubation period. Several of the new in-house tests had performance characteristics that were nearly as good as the commercial ELISAs. Finally, the in-house tests were evaluated for use as confirmatory tests following screening with the PrioCHECK^® and ID Screen^® FMDV NS commercial kits, to assess the diagnostic performance produced by a multiple testing strategy. The in-house tests could be used in series (to confirm) or in parallel (to augment) with the PrioCHECK^® and IDvet^® FMDV NS commercial kits, in order to improve either the specificity or sensitivity of the overall test system, although this comes at the cost of a reduction in the counterpart (sensitivity/specificity) parameter. Full article

(This article belongs to the Special Issue Global Foot-and-Mouth Disease Control)

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17 pages, 1568 KiB

Open AccessArticle

Development and Validation of a Mucosal Antibody (IgA) Test to Identify Persistent Infection with Foot-and-Mouth Disease Virus

by Jitendra K. Biswal, Antonello Di Nardo, Geraldine Taylor, David J. Paton and Satya Parida

Viruses 2021, 13(5), 814; https://doi.org/10.3390/v13050814 - 01 May 2021

Cited by 1 | Viewed by 2648

Abstract

It is well known that approximately 50% of cattle infected with foot-and-mouth disease (FMD) virus (FMDV) may become asymptomatic carrier (persistently infected) animals. Although transmission of FMDV from carrier cattle to naïve cattle has not been demonstrated experimentally, circumstantial evidence from field studies [...] Read more.

It is well known that approximately 50% of cattle infected with foot-and-mouth disease (FMD) virus (FMDV) may become asymptomatic carrier (persistently infected) animals. Although transmission of FMDV from carrier cattle to naïve cattle has not been demonstrated experimentally, circumstantial evidence from field studies has linked FMDV-carrier cattle to cause subsequent outbreaks. Therefore, the asymptomatic carrier state complicates the control and eradication of FMD. Current serological diagnosis using tests for antibodies to the viral non-structural proteins (NSP-ELISA) are not sensitive enough to detect all carrier animals, if persistently infected after vaccination and do not distinguish between carriers and non-carriers. The specificity of the NSP ELISA may also be reduced after vaccination, in particular after multiple vaccination. FMDV-specific mucosal antibodies (IgA) are not produced in vaccinated cattle but are elevated transiently during the acute phase of infection and can be detected at a high level in cattle persistently infected with FMDV, irrespective of their vaccination status. Therefore, detection of IgA by ELISA may be considered a diagnostic alternative to RT-PCR for assessing FMDV persistent infection in ruminants in both vaccinated and unvaccinated infected populations. This study reports on the development and validation of a new mucosal IgA ELISA for the detection of carrier animals using nasal, saliva, and oro-pharyngeal fluid (OPF) samples. The diagnostic performance of the IgA ELISA using nasal samples from experimentally vaccinated and infected cattle demonstrated a high level of specificity (99%) and an improved level of sensitivity (76.5%). Furthermore, the detection of carrier animals reached 96.9% when parallel testing of samples was carried out using both the IgA-ELISA and NSP-ELISA. Full article

(This article belongs to the Special Issue Global Foot-and-Mouth Disease Control)

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Review

Jump to: Research, Other

13 pages, 532 KiB

Open AccessReview

Targeted FMD Vaccines for Eastern Africa: The AgResults Foot and Mouth Disease Vaccine Challenge Project

by Jef M. Hammond, Badi Maulidi and Nina Henning

Viruses 2021, 13(9), 1830; https://doi.org/10.3390/v13091830 - 14 Sep 2021

Cited by 9 | Viewed by 5986

Abstract

As one of the most infectious livestock diseases in the world, foot and mouth disease (FMD) presents a constant global threat to animal trade and national economies. FMD remains a severe constraint on development and poverty reduction throughout the developing world due to [...] Read more.

As one of the most infectious livestock diseases in the world, foot and mouth disease (FMD) presents a constant global threat to animal trade and national economies. FMD remains a severe constraint on development and poverty reduction throughout the developing world due to many reasons, including the cost of control measures, closure of access to valuable global FMD-free markets for livestock products, production losses through reduced milk yield, reduced live weight gain, and the inability of infected livestock to perform traction. FMD virus infects a variety of cloven-hoofed animals, including cattle, sheep, goats, swine, all wild ruminants, and suidae, with high morbidity in adult animals. High mortality can occur in young animals due to myocarditis. FMD is endemic in Africa, most of Asia, the Middle East, and parts of South America. The global clustering of FMD viruses has been divided into seven virus pools, where multiple serotypes occur but within which are topotypes that remain mostly confined to that pool. Three pools cover Europe, the Middle East, and Asia; three pools cover Africa; and one pool covers the Americas. The highly infectious nature of FMDV, the existence of numerous continually circulating serotypes and associated topotypes, the potential for wildlife reservoirs, and the frequent emergence of new strains that are poorly matched to existing vaccines all serve to compound the difficulties faced by the governments of endemic countries to effectively control and reduce the burden of the disease at the national and regional levels. This clustering of viruses suggests that if vaccination is to be a major tool for control, each pool could benefit from the use of tailored or more specific vaccines relevant to the topotypes present in that pool, rather than a continued reliance on the currently more widely available vaccines. It should also be noted that, currently, there are varying degrees of effort to identify improved vaccines in different regions. There are relatively few targeted for use in Africa, while the developed world’s vaccine banks have a good stock of vaccines destined for emergency outbreak use in FMDV-free countries. The AgResults Foot and Mouth Disease (FMD) Vaccine Challenge Project (the “Project”) is an eight-year, US $17.68 million prize competition that supports the development and uptake of high-quality quadrivalent FMD vaccines tailored to meet the needs of Eastern Africa (EA). The Project targets the following Pool Four countries: Burundi, Ethiopia, Kenya, Rwanda, Tanzania and Uganda. The Project is being run in two phases: a development phase, which will encourage the production of regionally relevant vaccines, and a cost-share phase, designed to help to reduce the price of these vaccines in the marketplace to the end users, which is hoped will encourage broader uptake. Manufacturers can submit quadrivalent FMD vaccines containing serotypes A, O, SAT1, and SAT2, which will be assessed as relevant for use in the region through a unique component of the Project requiring the screening of vaccines against the Eastern Africa Foot and Mouth Disease Virus Reference Antigen Panel assembled by the World Reference Laboratory for FMD (WRLFMD), at the Pirbright Institute, UK, in collaboration with the OIE/FAO FMD Reference Laboratory Network. To be eligible for the Project, sera from vaccinated cattle will be used to evaluate serological responses of FMD vaccines for their suitability for use in Eastern African countries. If they pass a determined cut-off threshold, they will be confirmed as relevant for use in the region and will be entered into the Project’s cost-share phase. Full article

(This article belongs to the Special Issue Global Foot-and-Mouth Disease Control)

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Other

Jump to: Research, Review

2 pages, 714 KiB

Open AccessCorrection

Correction: Sarry et al. Host-Specific Interplay between Foot-and-Mouth Disease Virus 3D Polymerase and the Type-I Interferon Pathway. Viruses 2023, 15, 666

by Morgan Sarry, Grégory Caignard, Juliette Dupré, Stephan Zientara, Damien Vitour, Labib Bakkali Kassimi and Sandra Blaise-Boisseau

Viruses 2023, 15(11), 2137; https://doi.org/10.3390/v15112137 - 24 Oct 2023

Viewed by 432

Abstract

In the original publication [...] Full article

(This article belongs to the Special Issue Global Foot-and-Mouth Disease Control)

2 pages, 5029 KiB

Open AccessCorrection

Correction: King et al. Establishing an In Vitro System to Assess How Specific Antibodies Drive the Evolution of Foot-and-Mouth Disease Virus. Viruses 2022, 14, 1820

by David J. King, Graham Freimanis, Chris Neil, Andrew Shaw, Tobias J. Tuthill, Emma Laing, Donald P. King and Lidia Lasecka-Dykes

Viruses 2023, 15(2), 269; https://doi.org/10.3390/v15020269 - 18 Jan 2023

Viewed by 867

Abstract

In the original publication [...] Full article

(This article belongs to the Special Issue Global Foot-and-Mouth Disease Control)

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10 pages, 632 KiB

Open AccessBrief Report

Proof of Proficiency of Decentralized Foot-and-Mouth Disease Virus Diagnostics in Germany

by Hanna Keck, Bernd Hoffmann and Michael Eschbaumer

Viruses 2022, 14(5), 1098; https://doi.org/10.3390/v14051098 - 20 May 2022

Cited by 2 | Viewed by 1659

Abstract

A proficiency test was performed to verify that the regional veterinary laboratories in Germany can provide reliable foot-and-mouth disease virus (FMDV) diagnostics. Overall, 24 samples were to be analyzed for FMDV-specific nucleic acids by real-time RT-PCR, and 16 samples had to be tested [...] Read more.

A proficiency test was performed to verify that the regional veterinary laboratories in Germany can provide reliable foot-and-mouth disease virus (FMDV) diagnostics. Overall, 24 samples were to be analyzed for FMDV-specific nucleic acids by real-time RT-PCR, and 16 samples had to be tested by ELISA for antibodies against non-structural proteins of FMDV. For both methods, a range of dilutions of the original materials (inactivated FMDV vaccine or convalescent serum from infected animals, respectively) was prepared, and negative samples were included as well. All 23 participating laboratories were able to detect FMDV genome down to a dilution of 1:100,000 of the vaccine preparation. Even at a dilution of 1:1,000,000, FMDV genome was detected by more than half of the participants. With the antibody ELISA, all sera were correctly identified by all participating laboratories. No false-positive results were returned with either method. All participating laboratories were found to be fully proficient in FMDV diagnostics. Full article

(This article belongs to the Special Issue Global Foot-and-Mouth Disease Control)

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12 pages, 538 KiB

Open AccessBrief Report

A Vaccine Based on the A/ASIA/G-VII Lineage of Foot-and-Mouth Disease Virus Offers Low Levels of Protection against Circulating Viruses from the A/ASIA/Iran-05 lineage

by Nagendrakumar Balasubramanian Singanallur, Phaedra Lydia Eblé, Anna Barbara Ludi, Bob Statham, Abdelghani Bin-Tarif, Donald P. King, Aldo Dekker and Wilna Vosloo

Viruses 2022, 14(1), 97; https://doi.org/10.3390/v14010097 - 06 Jan 2022

Cited by 6 | Viewed by 2287

Abstract

The recent emergence and circulation of the A/ASIA/G-VII (A/G-VII) lineage of foot-and-mouth disease virus (FMDV) in the Middle East has resulted in the development of homologous vaccines to ensure susceptible animals are sufficiently protected against clinical disease. However, a second serotype A lineage [...] Read more.

The recent emergence and circulation of the A/ASIA/G-VII (A/G-VII) lineage of foot-and-mouth disease virus (FMDV) in the Middle East has resulted in the development of homologous vaccines to ensure susceptible animals are sufficiently protected against clinical disease. However, a second serotype A lineage called A/ASIA/Iran-05 (A/IRN/05) continues to circulate in the region and it is therefore imperative to ensure vaccine strains used will protect against both lineages. In addition, for FMDV vaccine banks that usually hold a limited number of strains, it is necessary to include strains with a broad antigenic coverage. To assess the cross protective ability of an A/G-VII emergency vaccine (formulated at 43 (95% CI 8–230) PD₅₀/dose as determined during homologous challenge), we performed a heterologous potency test according to the European Pharmacopoeia design using a field isolate from the A/IRN/05 lineage as the challenge virus. The estimated heterologous potency in this study was 2.0 (95% CI 0.4–6.0) PD₅₀/dose, which is below the minimum potency recommended by the World Organisation for Animal Health (OIE). Furthermore, the cross-reactive antibody titres against the heterologous challenge virus were poor (≤log₁₀ 0.9), even in those cattle that had received the full dose of vaccine. The geometric mean r₁-value was 0.2 (95% CI 0.03–0.8), similar to the potency ratio of 0.04 (95% CI 0.004–0.3). Vaccination decreased viraemia and virus excretion compared to the unvaccinated controls. Our results indicate that this A/G-VII vaccine does not provide sufficient protection against viruses belonging to the A/IRN/05 lineage and therefore the A/G-VII vaccine strain cannot replace the A/IRN/05 vaccine strain but could be considered an additional strain for use in vaccines and antigen banks. Full article

(This article belongs to the Special Issue Global Foot-and-Mouth Disease Control)

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