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Diagnostics, Vaccinology and Pathogenesis of Foot-and-Mouth Disease and Other Viral...
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Diagnostics, Vaccinology and Pathogenesis of Foot-and-Mouth Disease and Other Viral Vesicular Diseases of Livestock

A special issue of Pathogens (ISSN 2076-0817).

Deadline for manuscript submissions: closed (30 June 2020) | Viewed by 34911

Special Issue Editor

Dr. Charles Nfon

E-Mail Website
Guest Editor
National Centre for Foreign Animal Disease, Canadian Food Inspection Agency, 1015 Arlington Street, Winnipeg, MB, Canada
Interests: foot-and-mouth disease; vesicular diseases; diagnostics; immunopathogenesis; control

Special Issue Information

Dear Colleagues,

Massive research on foot-and-mouth disease continues to take place all over the world. Significant progress has been made in development and/or improvement of diagnostic tools for FMD. In addition, existing tests are continuously being evaluated for point-of-care use. These include lateral flow devices for detection of antigen or antibodies to FMDV, hand-held and portable molecular diagnostic tools among others.

Also, vaccines for FMD have been used to successfully control or eradicate the disease in Europe, most of South America and in specific portions of some FMD endemic countries. The widely used vaccine consists of adjuvanted inactivated whole virus antigen. An adenovirus-vectored vaccine has been licensed for potential emergency use in the USA. Other vaccine platforms have also been developed and tested but are yet to be licensed. However, there is a continuing need for vaccine development, especially towards a vaccine that could induce lifelong immunity with a single administration. Similarly, more research is needed to continue to elucidate the pathogenesis of FMD virus in domestic animals and the viral/host factors that contribute to virulence. This information can then be used to develop better immunotherapeutics and vaccines for FMD.

This special issue of Pathogens will focus on the recent developments in diagnostics, vaccinology and pathogenesis of foot-and-mouth disease and other viral vesicular diseases in livestock. Topics will therefore include

  • Diagnostics, with special interest in new field-deployable diagnostic tools showing successful application in endemic countries, comparison of various diagnostic tests in endemic countries or with samples from endemic countries
  • Vaccinology, including experimental vaccines that show potential for use in livestock, field validation of new vaccine platforms, new methods for vaccine matching etc
  • pathogenesis of FMD virus in domestic animals and the viral/host factors that contribute to the virulence

Dr. Charles Nfon
Guest Editor

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pathogens is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • FMD
  • diagnostics
  • vaccines
  • pathogenesis

Published Papers (9 papers)

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Research

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11 pages, 1405 KiB  
Article
Detection of Foot-and-Mouth Disease Virus in Swine Meat Juice
by Sean Yeo, Ming Yang, Martin Nyachoti, Rolf Rauh, Johnny D. Callahan and Charles Nfon
Pathogens 2020, 9(6), 424; https://doi.org/10.3390/pathogens9060424 - 29 May 2020
Cited by 7 | Viewed by 3395
Abstract
Foot-and-mouth disease virus (FMDV) is a highly contagious agent that impacts livestock industries worldwide, leading to significant financial loss. Its impact can be avoided or minimized if the virus is detected early. FMDV detection relies on vesicular fluid, epithelial tags, swabs, serum, and [...] Read more.
Foot-and-mouth disease virus (FMDV) is a highly contagious agent that impacts livestock industries worldwide, leading to significant financial loss. Its impact can be avoided or minimized if the virus is detected early. FMDV detection relies on vesicular fluid, epithelial tags, swabs, serum, and other sample types from live animals. These samples might not always be available, necessitating the use of alternative sample types. Meat juice (MJ), collected after freeze-thaw cycles of skeletal muscle, is a potential sample type for FMDV detection, especially when meat is illegally imported. We have performed experiments to evaluate the suitability of MJ for FMDV detection. MJ was collected from pigs that were experimentally infected with FMDV. Ribonucleic acid (RNA) was extracted from MJ, sera, oral swabs, and lymph nodes from the same animals and tested for FMDV by real-time reverse transcription polymerase chain reaction (rRT-PCR). MJ was also tested for FMDV antigen by Lateral Flow Immunoassay (LFI). FMDV RNA was detected in MJ by rRT-PCR starting at one day post infection (DPI) and as late as 21 DPI. In contrast, FMDV RNA was detected in sera at 1–7 DPI. Antigen was also detected in MJ at 1–9 DPI by LFI. Live virus was not isolated directly from MJ, but was recovered from the viral genome by transfection into susceptible cells. The data show that MJ is a good sample type for FMDV detection. Full article
(This article belongs to the Special Issue Diagnostics, Vaccinology and Pathogenesis of Foot-and-Mouth Disease and Other Viral Vesicular Diseases of Livestock)
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15 pages, 2322 KiB  
Article
GoPrime: Development of an In Silico Framework to Predict the Performance of Real-Time PCR Primers and Probes Using Foot-and-Mouth Disease Virus as a Model
by Emma L A Howson, Richard J Orton, Valerie Mioulet, Tiziana Lembo, Donald P King and Veronica L Fowler
Pathogens 2020, 9(4), 303; https://doi.org/10.3390/pathogens9040303 - 20 Apr 2020
Cited by 3 | Viewed by 3946
Abstract
Real-time PCR (rPCR) is a widely accepted diagnostic tool for the detection and quantification of nucleic acid targets. In order for these assays to achieve high sensitivity and specificity, primer and probe-template complementarity is essential; however, mismatches are often unavoidable and can result [...] Read more.
Real-time PCR (rPCR) is a widely accepted diagnostic tool for the detection and quantification of nucleic acid targets. In order for these assays to achieve high sensitivity and specificity, primer and probe-template complementarity is essential; however, mismatches are often unavoidable and can result in false-negative results and errors in quantifying target sequences. Primer and probe sequences therefore require continual evaluation to ensure they remain fit for purpose. This paper describes the development of a linear model and associated computational tool (GoPrime) designed to predict the performance of rPCR primers and probes across multiple sequence data. Empirical data were generated using DNA oligonucleotides (n = 90) that systematically introduced variation in the primer and probe target regions of a diagnostic assay routinely used to detect foot-and-mouth disease virus (FMDV); an animal virus that exhibits a high degree of sequence variability. These assays revealed consistent impacts of patterns of substitutions in primer and probe-sites on rPCR cycle threshold (CT) and limit of detection (LOD). These data were used to populate GoPrime, which was subsequently used to predict rPCR results for DNA templates (n = 7) representing the natural sequence variability within FMDV. GoPrime was also applicable to other areas of the FMDV genome, with predictions for the likely targets of a FMDV-typing assay consistent with published experimental data. Although further work is required to improve these tools, including assessing the impact of primer-template mismatches in the reverse transcription step and the broader impact of mismatches for other assays, these data support the use of mathematical models for rapidly predicting the performance of rPCR primers and probes in silico. Full article
(This article belongs to the Special Issue Diagnostics, Vaccinology and Pathogenesis of Foot-and-Mouth Disease and Other Viral Vesicular Diseases of Livestock)
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21 pages, 3557 KiB  
Article
Into the Deep (Sequence) of the Foot-and-Mouth Disease Virus Gene Pool: Bottlenecks and Adaptation during Infection in Naïve and Vaccinated Cattle
by Ian Fish, Carolina Stenfeldt, Rachel M. Palinski, Steven J. Pauszek and Jonathan Arzt
Pathogens 2020, 9(3), 208; https://doi.org/10.3390/pathogens9030208 - 12 Mar 2020
Cited by 9 | Viewed by 3194
Abstract
Foot-and-mouth disease virus (FMDV) infects hosts as a population of closely related viruses referred to as a quasispecies. The behavior of this quasispecies has not been described in detail in natural host species. In this study, virus samples collected from vaccinated and non-vaccinated [...] Read more.
Foot-and-mouth disease virus (FMDV) infects hosts as a population of closely related viruses referred to as a quasispecies. The behavior of this quasispecies has not been described in detail in natural host species. In this study, virus samples collected from vaccinated and non-vaccinated cattle up to 35 days post-experimental infection with FMDV A24-Cruzeiro were analyzed by deep-sequencing. Vaccination induced significant differences compared to viruses from non-vaccinated cattle in substitution rates, entropy, and evidence for adaptation. Genomic variation detected during early infection reflected the diversity inherited from the source virus (inoculum), whereas by 12 days post infection, dominant viruses were defined by newly acquired mutations. Mutations conferring recognized fitness gain occurred and were associated with selective sweeps. Persistent infections always included multiple FMDV subpopulations, suggesting distinct foci of infection within the nasopharyngeal mucosa. Subclinical infection in vaccinated cattle included very early bottlenecks associated with reduced diversity within virus populations. Viruses from both animal cohorts contained putative antigenic escape mutations. However, these mutations occurred during later stages of infection, at which time transmission is less likely to occur. This study improves upon previously published work by analyzing deep sequences of samples, allowing for detailed characterization of FMDV populations over time within multiple hosts. Full article
(This article belongs to the Special Issue Diagnostics, Vaccinology and Pathogenesis of Foot-and-Mouth Disease and Other Viral Vesicular Diseases of Livestock)
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13 pages, 1595 KiB  
Article
Evaluation of Quality Control Methods for Foot-And-Mouth Disease Vaccines by High-Performance Liquid Chromatography
by Mun-Hyeon Kim, Seon-Jong Yun, Yeon-Hee Kim, Hyang-Sim Lee, Ji-Yeon Kim, Ji-Ye Kim, JeongWoo Kang, Yong-Sang Kim and Min-Goo Seo
Pathogens 2020, 9(3), 194; https://doi.org/10.3390/pathogens9030194 - 05 Mar 2020
Cited by 4 | Viewed by 3500
Abstract
Foot-and-mouth disease (FMD) is considered one of the highly contagious viral infections affecting livestock. In Korea, an FMD vaccination policy has been implemented nationwide since 2010 for the prevention and control of FMD. Since the vaccines are imported from various countries, standardized quality [...] Read more.
Foot-and-mouth disease (FMD) is considered one of the highly contagious viral infections affecting livestock. In Korea, an FMD vaccination policy has been implemented nationwide since 2010 for the prevention and control of FMD. Since the vaccines are imported from various countries, standardized quality control measures are critical. In this study, we aimed to validate a high-performance liquid chromatography (HPLC) device in the Animal and Plant Quarantine Agency lab and identify an appropriate FMD vaccine pretreatment method for HPLC—a simple, reliable, and practical method to measure antigen content. Based on the analyses of specificity, linearity, accuracy, repeatability, intermediate precision, limits of detection, and limits of quantification using FMD standard samples, we validated the method using a standard material. Overall, we confirmed that the HPLC technique is effective for the quantitative assessment of the FMD virus 146S antigen in Korea. Using commercial FMD vaccines, we evaluated three separation methods and identified the method using n-pentanol and trichloroethylene as optimal for HPLC analysis. Our HPLC method was effective for the analytical detection of the antigen content in FMD vaccine, and it may be useful as a reference method for national lot-release testing. Full article
(This article belongs to the Special Issue Diagnostics, Vaccinology and Pathogenesis of Foot-and-Mouth Disease and Other Viral Vesicular Diseases of Livestock)
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11 pages, 726 KiB  
Article
High-Resolution Composition Analysis of an Inactivated Polyvalent Foot-and-Mouth Disease Vaccine
by Leonie F. Forth, Dirk Höper, Martin Beer and Michael Eschbaumer
Pathogens 2020, 9(1), 63; https://doi.org/10.3390/pathogens9010063 - 16 Jan 2020
Cited by 6 | Viewed by 2799
Abstract
Appropriate vaccine selection is crucial in the control of foot-and-mouth disease (FMD). Vaccination can prevent clinical disease and reduces viral shedding, but there is a lack of cross-protection between the seven serotypes and their sublineages, making the selection of an adequately protective vaccine [...] Read more.
Appropriate vaccine selection is crucial in the control of foot-and-mouth disease (FMD). Vaccination can prevent clinical disease and reduces viral shedding, but there is a lack of cross-protection between the seven serotypes and their sublineages, making the selection of an adequately protective vaccine difficult. Since the exact composition of their vaccines is not consistently disclosed by all manufacturers, incompatibility of the strains used for vaccination with regionally circulating strains can cause vaccination campaigns to fail. Here, we present a deep sequencing approach for polyvalent inactivated FMD vaccines that can identify all component strains by their genome sequences. The genomes of all strains of a commercial pentavalent FMD vaccine were de novo assembled and the vaccine composition determined semi-quantitatively. The genome assembly required high stringency parameters to prevent misassemblies caused by conserved regions of the genome shared by related strains. In contrast, reference-guided assembly is only recommended in cases where the number of strains is previously known and appropriate reference sequences are available. The presented approach can be applied not only to any inactivated whole-virus FMD vaccine but also to vaccine quality testing in general and allows for better decision-making for vaccines with an unknown composition. Full article
(This article belongs to the Special Issue Diagnostics, Vaccinology and Pathogenesis of Foot-and-Mouth Disease and Other Viral Vesicular Diseases of Livestock)
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12 pages, 1269 KiB  
Article
Development of Monoclonal Antibody Specific to Foot-and-Mouth Disease Virus Type A for Serodiagnosis
by Quyen Thi Nguyen, Jihyun Yang, Jae-Won Byun, Hyun Mi Pyo, Mi-Young Park, Bok Kyung Ku, Jinju Nah, Soyoon Ryoo, Sung-Hwan Wee, Kang-Seuk Choi and Haryoung Poo
Pathogens 2019, 8(4), 301; https://doi.org/10.3390/pathogens8040301 - 17 Dec 2019
Cited by 7 | Viewed by 3715
Abstract
Foot-and-mouth disease (FMD) is a highly contagious and economically devastating disease affecting cloven-hoofed livestock worldwide. FMD virus (FMDV) type A is one of the most common causes of FMD outbreaks among the seven FMDV serotypes, and its serological diagnosis is therefore important to [...] Read more.
Foot-and-mouth disease (FMD) is a highly contagious and economically devastating disease affecting cloven-hoofed livestock worldwide. FMD virus (FMDV) type A is one of the most common causes of FMD outbreaks among the seven FMDV serotypes, and its serological diagnosis is therefore important to confirm FMDV type A infection and to determine FMD vaccine efficacy. Here, we generated monoclonal antibodies (mAbs) specific to FMDV type A via hybridoma systems using an inactivated FMDV type A (A22/Iraq/1964) and found 4 monoclones (#29, #106, #108, and #109) with high binding reactivity to FMDV type A among 594 primary clones. In particular, the #106 mAb had a higher binding reactivity to the inactivated FMDV type A than the other mAbs and a commercial mAb. Moreover, the #106 mAb showed no cross-reactivity to inactivated FMDV type South African territories 1, 2, and 3, and low reactivity to inactivated FMDV type O (O1 Manisa). Importantly, the solid-phase competitive ELISA (SPCE) using horseradish peroxidase (HRP)-conjugated #106 mAb detected FMDV type A-specific Abs in sera from FMD type A-vaccinated cattle more effectively than a commercial SPCE. These results suggest that the newly developed FMDV type A-specific mAb might be useful for diagnostic approaches for detecting Abs against FMDV type A. Full article
(This article belongs to the Special Issue Diagnostics, Vaccinology and Pathogenesis of Foot-and-Mouth Disease and Other Viral Vesicular Diseases of Livestock)
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7 pages, 192 KiB  
Article
A Rational Explanation of Limited FMD Vaccine Uptake in Endemic Regions
by Ashley F. Railey and Thomas L. Marsh
Pathogens 2019, 8(4), 181; https://doi.org/10.3390/pathogens8040181 - 10 Oct 2019
Cited by 9 | Viewed by 2493
Abstract
Vaccination for foot-and-mouth (FMD) disease remains low in parts of Africa despite the existence of vaccines. In East Africa, the presence of multiple virus serotypes and sub-types makes matching a vaccine with the circulating virus type in the field, or providing a high [...] Read more.
Vaccination for foot-and-mouth (FMD) disease remains low in parts of Africa despite the existence of vaccines. In East Africa, the presence of multiple virus serotypes and sub-types makes matching a vaccine with the circulating virus type in the field, or providing a high potency vaccine, a challenge. In this paper we use game theory to show that the resulting vaccine uncertainty associated with these vaccination conditions in an endemic setting help explain the low vaccine uptake. We evaluate vaccination for FMD in the context of East Africa due to FMD being endemic in the region, the diversity of FMD virus types, and barriers to implementing other disease control measures, such as controlled movements. We incorporate these conditions into a vaccination game setting and compare the payoffs to those of a traditional vaccination game for seasonal influenza and commercial livestock vaccination in a developed country context. In showing that vaccination provides households with a lower payoff than not vaccinating, our simple game theoretical explanation supports existing evidence calling for improved vaccine quality and efforts to enhance surveillance to provide early information on disease status. Full article
(This article belongs to the Special Issue Diagnostics, Vaccinology and Pathogenesis of Foot-and-Mouth Disease and Other Viral Vesicular Diseases of Livestock)

Review

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27 pages, 2898 KiB  
Review
The Carrier Conundrum; A Review of Recent Advances and Persistent Gaps Regarding the Carrier State of Foot-and-Mouth Disease Virus
by Carolina Stenfeldt and Jonathan Arzt
Pathogens 2020, 9(3), 167; https://doi.org/10.3390/pathogens9030167 - 28 Feb 2020
Cited by 35 | Viewed by 8027
Abstract
The existence of a prolonged, subclinical phase of foot-and-mouth disease virus (FMDV) infection in cattle was first recognized in the 1950s. Since then, the FMDV carrier state has been a subject of controversy amongst scientists and policymakers. A fundamental conundrum remains in the [...] Read more.
The existence of a prolonged, subclinical phase of foot-and-mouth disease virus (FMDV) infection in cattle was first recognized in the 1950s. Since then, the FMDV carrier state has been a subject of controversy amongst scientists and policymakers. A fundamental conundrum remains in the discordance between the detection of infectious FMDV in carriers and the apparent lack of contagiousness to in-contact animals. Although substantial progress has been made in elucidating the causal mechanisms of persistent FMDV infection, there are still critical knowledge gaps that need to be addressed in order to elucidate, predict, prevent, and model the risks associated with the carrier state. This is further complicated by the occurrence of a distinct form of neoteric subclinical infection, which is indistinguishable from the carrier state in field scenarios, but may have substantially different epidemiological properties. This review summarizes the current state of knowledge of the FMDV carrier state and identifies specific areas of research in need of further attention. Findings from experimental investigations of FMDV pathogenesis are discussed in relation to experience gained from field studies of foot-and-mouth disease. Full article
(This article belongs to the Special Issue Diagnostics, Vaccinology and Pathogenesis of Foot-and-Mouth Disease and Other Viral Vesicular Diseases of Livestock)
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Other

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8 pages, 437 KiB  
Brief Report
Foot-and-Mouth Disease Virus Lacking the Leader Protein and Containing Two Negative DIVA Markers (FMDV LL3B3D A24) Is Highly Attenuated in Pigs
by Michael Eschbaumer, Veronika Dill, Jolene C. Carlson, Jonathan Arzt, Carolina Stenfeldt, Peter W. Krug, John M. Hardham, Jacob E. Stegner, Luis L. Rodriguez and Elizabeth Rieder
Pathogens 2020, 9(2), 129; https://doi.org/10.3390/pathogens9020129 - 17 Feb 2020
Cited by 4 | Viewed by 2917
Abstract
Inactivated whole-virus vaccines are widely used for the control of foot-and-mouth disease (FMD). Their production requires the growth of large quantities of virulent FMD virus in biocontainment facilities, which is expensive and carries the risk of an inadvertent release of virus. Attenuated recombinant [...] Read more.
Inactivated whole-virus vaccines are widely used for the control of foot-and-mouth disease (FMD). Their production requires the growth of large quantities of virulent FMD virus in biocontainment facilities, which is expensive and carries the risk of an inadvertent release of virus. Attenuated recombinant viruses lacking the leader protease coding region have been proposed as a safer alternative for the production of inactivated FMD vaccines (Uddowla et al., 2012, J Virol 86:11675-85). In addition to the leader deletion, the marker vaccine virus FMDV LL3BPVKV3DYR A24 encodes amino acid substitutions in the viral proteins 3B and 3D that allow the differentiation of infected from vaccinated animals and has been previously shown to be effective in cattle and pigs. In the present study, two groups of six pigs each were inoculated with live FMDV LL3BPVKV3DYR A24 virus either intradermally into the heel bulb (IDHB) or by intra-oropharyngeal (IOP) deposition. The animals were observed for 3 or 5 days after inoculation, respectively. Serum, oral and nasal swabs were collected daily and a thorough postmortem examination with tissue collection was performed at the end of the experiment. None of the animals had any signs of disease or virus shedding. Virus was reisolated from only one serum sample (IDHB group, sample taken on day 1) and one piece of heel bulb skin from the inoculation site of another animal (IDHB group, necropsy on day 3), confirming that FMDV LL3BPVKV3DYR A24 is highly attenuated in pigs. Full article
(This article belongs to the Special Issue Diagnostics, Vaccinology and Pathogenesis of Foot-and-Mouth Disease and Other Viral Vesicular Diseases of Livestock)
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