Publications

The Pirbright Institute publication directory contains details of selected publications written by our researchers.

There were a total of 2431 results for your search.

Abstract

Many disease outbreaks, including Covid-19, are caused by viruses that have jumped from animals to humans. At the Pirbright Institute in the UK, Dr Rebecca McLean and Professor Simon Graham are studying one particular virus which did this in 1998 and continues to pose a threat today. They have developed and tested potential vaccines which, if delivered to pigs, could prevent future outbreaks of Nipah virus in humans.

Fana E, Shikongo B, Banda F, Qua M, Knowles N J, Shilongo A, Khaiseb S, Kapapero J K, Shoombe K K, Wadsworth J, Zaire G, Mokopasetso M, Kabajani J, Kabilika S, Di Nardo A, Hikufe E H, King D P (2022)

The first detection of a serotype O foot-and-mouth disease virus in Namibia

Transboundary and Emerging Diseases early view
Publisher’s version: https://doi.org/10.1111/tbed.14561

Abstract

This report describes the molecular characterization of a serotype O foot-and-mouth disease virus (FMDV) recovered from a field outbreak in the Zambezi region, Namibia during July 2021. Sequence analysis demonstrates that this FMDV belongs to the O/EA-2 topotype sharing closest nucleotide identity (99.5%) to FMD viruses collected since 2018 in Zambia. This is the first detection of serotype O in Namibia, and together with the cases that have been recently detected in southern Zambia, represent the first time that this serotype has been detected in the Southern African FMD endemic pool since 2000, when a virus of Asian origin (O/ME-SA/PanAsia) caused an outbreak in South Africa. This incursion poses a new threat for the region and the potential onward spread of O/EA-2 will now need to be closely monitored since serotype O vaccines are not widely used in Namibia, nor in neighbouring countries.

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 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.

Abstract

Foot-and-mouth disease (FMD) has large economic consequences in livestock systems, which must be robustly assessed to support disease control policy. This study described and assessed methods used within economic analyses of FMD and its control in endemic contexts. A systematic literature search was conducted in six academic search engines. Studies were included if they applied an economic analysis to a context with endemic FMD, producing a result articulated as a monetary figure. Data collected from each article included country of study, animal population, geographical level of analysis, time horizon and type of economic analysis. Each paper was scored using a quality assessment tool containing a checklist of 42 reporting criteria. Sixty-four articles were included, from 12,087 identified in the searches, describing results for 26 countries. Over half of the articles (56%) described economic impact of FMD retrospectively, often only accounting for a selection of direct costs at farm or household level. Median quality score calculated was 41% (range 8%-86%). Methods were generally poorly reported, confirming previously described difficulties in using published data to evaluate economic impact of endemic FMD. Few papers included disaggregation of public and private costs, or benefits, of FMD control, or accounted for economic or social influences of scale in vaccination programmes. Many of the studies included had gaps in both premise and methodology. This risks inefficient resource allocation if these analyses are used when planning and budgeting FMD control programmes in endemic contexts.

Canini L, Blaise-Boisseau S, Wadsworth J, Nardo A D, Shaw A, Romey A, Relmy A, Bernelin-Cottet C, Salomez A L, Haegeman A, Ularamu H, Lefebvre D, De Clercq K, Mioulet V, Brocchi E, Pezzoni G, Nfon C, King D, Durand B, Knowles N, Kassimi L B, Benfrid S (2022)

Identification of diffusion routes of O/EA-3 topotype of foot-and-mouth disease virus in Africa and Western Asia between 1974 and 2019 - a phylogeographic analysis

Transboundary and Emerging Diseases early view
Publisher’s version: https://doi.org/10.1111/tbed.14562

Abstract

Foot-and-mouth disease (FMD) affects the livestock industry and socio-economic sustainability of many African countries. The success of FMD control programs in Africa depends largely on understanding the dynamics of FMD virus (FMDV) spread. In light of the recent outbreaks of FMD that affected the North-Western African countries in 2018 and 2019, we investigated the evolutionary phylodynamics of the causative serotype O viral strains all belonging to the East-Africa 3 topotype (O/EA-3). We analyzed a total of 489 sequences encoding the FMDV VP1 genome region generated from samples collected from 25 African and Western Asian countries between 1974 and 2019. Using Bayesian evolutionary models on genomic and epidemiological data, we inferred the routes of introduction and migration of the FMDV O/EA-3 topotype at the inter-regional scale. We inferred a mean substitution rate of 6.64 10(-3) nt/site/year and we predicted that the most recent common ancestor (MRCA) for our panel of samples circulated between February 1967 and November 1973 in Yemen, likely reflecting the epidemiological situation in under sampled cattle-exporting East African countries. Our study also reinforces the role previously described of Sudan and South Sudan as a frequent source of FMDVs spread. In particular, we identified two transboundary routes of O/EA-3 diffusion: the first from Sudan to North-East Africa, and from the latter into Israel and Palestine AT; a second from Sudan to Nigeria, Cameroon, and from there to further into West and North-West Africa. This study highlights the necessity to reinforce surveillance at an inter-regional scale in Africa and Western Asia, in particular along the identified migration routes for the implementation of efficient control measures in the fight against FMD.

Abstract

Duck enteritis virus (DEV) and Pasteurella multocida, the causative agent of duck plague and fowl cholera, are acute contagious diseases and leading causes of morbidity and mortality in duck. The NHEJ-CRISPR/Cas9-mediated gene editing strategy, accompanied with the Cre–Lox system, have been employed in the present study to show that two new sites at UL55-LORF11 and UL44-44.5 loci in the genome of the attenuated Jansen strain of DEV can be used for the stable expression of the outer membrane protein H (ompH) gene of P. multocida that could be used as a bivalent vaccine candidate with the potential of protecting ducks simultaneously against major viral and bacterial pathogens. The two recombinant viruses, DEV-OmpH-V5-UL55-LORF11 and DEV-OmpH-V5-UL44-44.5, with the insertion of ompH-V5 gene at the UL55-LORF11 and UL44-44.5 loci respectively, showed similar growth kinetics and plaque size, compared to the wildtype virus, confirming that the insertion of the foreign gene into these did not have any detrimental effects on DEV. This is the first time the CRISPR/Cas9 system has been applied to insert a highly immunogenic gene from bacteria into the DEV genome rapidly and efficiently. This approach offers an efficient way to introduce other antigens into the DEV genome for multivalent vector. 

Abstract

In this study, we developed a new recombinant virus rHVT-F using a Turkey herpesvirus (HVT) vector, expressing the fusion (F) protein of the genotype XII Newcastle disease virus (NDV) circulating in Peru. We evaluated the viral shedding and efficacy against the NDV genotype XII challenge in specific pathogen-free (SPF) chickens. The F protein expression cassette was inserted in the unique long (UL) UL45–UL46 intergenic locus of the HVT genome by utilizing a clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 gene-editing technology via a non-homologous end joining (NHEJ) repair pathway. The rHVT-F virus, which expressed the F protein stably in vitro and in vivo, showed similar growth kinetics to the wild-type HVT (wtHVT) virus. The F protein expression of the rHVT-F virus was detected by an indirect immunofluorescence assay (IFA), Western blotting, and a flow cytometry assay. The presence of an NDV-specific IgY antibody was detected in serum samples by an enzyme-linked immunosorbent assay (ELISA) in SPF chickens vaccinated with the rHVT-F virus. In the challenge experiment, the rHVT-F vaccine fully protects a high, and significantly reduced, virus shedding in oral at 5 days post-challenge (dpc). In conclusion, this new rHVT-F vaccine candidate is capable of fully protecting SPF chickens against the genotype XII challenge.

Abstract

African swine fever virus (ASFV) has a major global economic impact. With a case fatality in domestic pigs approaching 100%, it currently presents the largest threat to animal farming. Although genomic differences between attenuated and highly virulent ASFV strains have been identified, the molecular determinants for virulence at the level of gene expression have remained opaque. Here we characterise the transcriptome of ASFV genotype II Georgia 2007/1 (GRG) during infection of the physiologically relevant host cells, porcine macrophages. In this study we applied Cap Analysis Gene Expression sequencing (CAGE-seq) to map the 5' ends of viral mRNAs at 5 and 16 hours post-infection. A bioinformatics analysis of the sequence context surrounding the transcription start sites (TSSs) enabled us to characterise the global early and late promoter landscape of GRG. We compared transcriptome maps of the GRG isolate and the lab-attenuated BA71V strain that highlighted GRG virulent-specific transcripts belonging to multigene families, including two predicted MGF 100 genes I7L and I8L. In parallel, we monitored transcriptome changes in the infected host macrophage cells. Of the 9,384 macrophage genes studied, transcripts for 652 host genes were differentially regulated between 5 and 16 hours-post-infection compared with only 25 between uninfected cells and 5 hours post-infection. NF-kB activated genes and lysosome components like S100 were upregulated, and chemokines such as CCL24, CXCL2, CXCL5 and CXCL8 downregulated. African swine fever virus (ASFV) causes haemorrhagic fever in domestic pigs with case fatality rates approaching 100%, and no approved vaccines or antivirals. The highly-virulent ASFV Georgia 2007/1 strain (GRG) was the first isolated when ASFV spread from Africa to the Caucasus region in 2007. Then spreading through Eastern Europe, and more recently across Asia. We used an RNA-based next generation sequencing technique called CAGE-seq to map the starts of viral genes across the GRG DNA genome. This has allowed us to investigate which viral genes are expressed during early or late stages of infection and how this is controlled, comparing their expression to the non-virulent ASFV-BA71V strain to identify key genes that play a role in virulence. In parallel we investigated how host cells respond to infection, which revealed how the ASFV suppresses components of the host immune response to ultimately win the arms race against its porcine host.

Gonzalez M A, Stokes J E, Bravo-Barriga D (2022)

Diversity and abundance of tabanids in Northern Spain

Parasitology Research 121 (1), 87-96

Abstract

Tabanids (Diptera: Tabanidae) are large haematophagous flies that cause both direct (by biting nuisance) and indirect (primarily by mechanical transmission of diseases) damage to host species. Research studies on this family have received little attention in some parts of Europe. Our aims were to characterise the species richness, abundance, and peak of activity of tabanid fly species in a region of Northern Spain. Home-made canopy traps, sweep nets, and Malaise traps were employed for the collection of tabanids across four cattle farms, two equestrian centres, and two golf courses during a 3-month period in the summer of 2020. A total of 300 specimens of 27 tabanid species belonging to eight genera were identified. The most prevalent species were Haematopota pluvialis (23.3%), Tabanus eggeri (20.0%), and Tabanus bromius (8.0%). The former species was recorded biting humans and therefore should be considered of relevance to public health. Tabanids were more diverse and abundant in scrubland and grazing pastures [relative abundance (RA) =  > 10%; species richness (S) = 8–12; Shannon-Index (H´) = 1.5 − 2.1] compared to crop landscapes (RA =  < 1%; S = 0–1; H´ = 0) according to canopy traps. The tabanid population dynamics was determined to be short, with the greatest abundance and diversity concentrated in mid-late July. This study updates the checklist of this Diptera group in the Northern Spain from nine known extant species to 31 species, providing the first data on the summer peaks of activity of tabanids for this region.

Abstract

T cells are an essential component of the adaptive immune system. Over the last 15 years, a constantly growing toolbox with which to study T cell biology in pigs has allowed detailed investigations on these cells in various viral and bacterial infections. This review provides an overview on porcine CD4, CD8, and γδ T cells and the current knowledge on the differentiation of these cells following antigen encounter. Where available, the responses of these cells to viral infections like porcine reproductive and respiratory syndrome virus, classical swine fever virus, swine influenza A virus, and African swine fever virus are outlined. In addition, knowledge on the porcine T cell response to bacterial infections like Actinobacillus pleuropneumoniae and Salmonella Typhimurium is reviewed. For CD4 T cells, the response to the outlined infections is reflected toward the Th1/Th2/Th17/Tfh/Treg paradigm for functional differentiation.

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