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

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Leftwich P T, Clarke N V E, Hutchings M I, Chapman T (2017)

Gut microbiomes and reproductive isolation in Drosophila

Proceedings of the National Academy of Sciences early view,


Experimental studies of the evolution of reproductive isolation (RI) in real time are a powerful way in which to reveal fundamental, early processes that initiate divergence. In a classic speciation experiment, populations of Drosophila pseudoobscura were subjected to divergent dietary selection and evolved significant positive assortative mating by diet. More recently, a direct role for the gut microbiome in determining this type of RI in Drosophila melanogaster has been proposed. Manipulation of the diet, and hence the gut microbiome, was reported to result in immediate assortative mating by diet, which could be eliminated by reducing gut microbes using antibiotics and recreated by adding back Lactobacillus plantarum. We suggest that the evolutionary significance of this result is unclear. For example, in D. melanogaster, the microbiome is reported as flexible and largely environmentally determined. Therefore, microbiome-mediated RI would be transient and would break down under dietary variation. In the absence of evolutionary coassociation or recurrent exposure between host and microbiome, there are no advantages for the gut bacteria or host in effecting RI. To explore these puzzling effects and their mechanisms further, we repeated the tests for RI associated with diet-specific gut microbiomes in D. melanogaster. Despite observing replicable differences in the gut microbiomes of flies maintained on different diets, we found no evidence for diet-associated RI, for any role of gut bacteria, or for L. plantarum specifically. The results suggest that there is no general role for gut bacteria in driving the evolution of RI in this species and resolve an evolutionary riddle.

Guinat C, Porphyre T, Gogin A, Dixon L K, Pfeiffer D U, Gubbins S (2017)

Inferring within-herd transmission parameters for African swine fever virus using mortality data from outbreaks in the Russian Federation

Transboundary and Emerging Diseases early view,


Mortality data are routinely collected for many livestock and poultry species, and they are often used for epidemiological purposes, including estimating transmission parameters. In this study, we infer transmission rates for African swine fever virus (ASFV), an important transboundary disease of swine, using mortality data collected from nine pig herds in the Russian Federation with confirmed outbreaks of ASFV. Parameters in a stochastic model for the transmission of ASFV within a herd were estimated using approximate Bayesian computation. Estimates for the basic reproduction number varied amongst herds, ranging from 4.4 to 17.3. This was primarily a consequence of differences in transmission rate (range: 0.7–2.2), but also differences in the mean infectious period (range: 4.5–8.3 days). We also found differences amongst herds in the mean latent period (range: 5.8–9.7 days). Furthermore, our results suggest that ASFV could be circulating in a herd for several weeks before a substantial increase in mortality is observed in a herd, limiting the usefulness of mortality data as a means of early detection of an outbreak. However, our results also show that mortality data are a potential source of data from which to infer transmission parameters, at least for diseases which cause high mortality.

Goller K V, Dill V, Madi M, Martin P, Van der Stede Y, Vandenberge V, Haas B, Van Borm S, Koenen F, Kasanga C J, Ndusilo N, Beer M, Liu L, Mioulet V, Armson B, King D P, Fowler V L (2017)

Rapid and simple detection of foot-and-mouth disease virus: Evaluation of a cartridge-based molecular detection system for use in basic laboratories

Transboundary and Emerging Diseases early view,


Highly contagious transboundary animal diseases such as foot-and-mouth disease (FMD) are major threats to the productivity of farm animals. To limit the impact of outbreaks and to take efficient steps towards a timely control and eradication of the disease, rapid and reliable diagnostic systems are of utmost importance. Confirmatory diagnostic assays are typically performed by experienced operators in specialized laboratories, and access to this capability is often limited in the developing countries with the highest disease burden. Advances in molecular technologies allow implementation of modern and reliable techniques for quick and simple pathogen detection either in basic laboratories or even at the pen-side. Here, we report on a study to evaluate a fully automated cartridge-based real-time RT-PCR diagnostic system (Enigma MiniLab®) for the detection of FMD virus (FMDV). The modular system integrates both nucleic acid extraction and downstream real-time RT-PCR (rRT-PCR). The analytical sensitivity of this assay was determined using serially diluted culture grown FMDV, and the performance of the assay was evaluated using a selected range of FMDV positive and negative clinical samples of bovine, porcine and ovine origin. The robustness of the assay was evaluated in an international inter-laboratory proficiency test and by deployment into an African laboratory. It was demonstrated that the system is easy to use and can detect FMDV with high sensitivity and specificity, roughly on par with standard laboratory methods. This cartridge-based automated real-time RT-PCR system for the detection of FMDV represents a reliable and easy to use diagnostic tool for the early and rapid disease detection of acutely infected animals even in remote areas. This type of system could be easily deployed for routine surveillance within endemic regions such as Africa or could alternatively be used in the developed world.

Lyons N A, Ludi A B, Wilsden G, Hamblin P, Qasim I A, Gubbins S, King D P (2017)

Evaluation of a polyvalent foot-and-mouth disease virus vaccine containing A Saudi-95 against field challenge on large-scale dairy farms in Saudi Arabia with the emerging A/ASIA/G-VII viral lineage

Vaccine early view,


In 2015, foot-and-mouth disease (FMD) viruses of the A/ASIA/G-VII lineage emerged from the Indian sub-continent to cause outbreaks in the Middle and Near East. A factor which has been proposed to have contributed to the rapid spread of this lineage is the poor in vitro vaccine-match of field isolates to vaccine strains that are commonly used in the region. This study used data from outbreaks on four large-scale dairy farms using routine vaccination in Saudi Arabia, to evaluate the impact of vaccination and learn how to manage outbreaks more effectively in this setting. This evaluation also included an assessment of vaccine-induced neutralisation titres to the vaccine and field strains on a related farm with no history of FMD that employed an identical vaccination schedule. The incidence risk among exposed groups ranged from 2.6 to 20.1% and was significantly higher among youngstock (18.7%) compared to adults (7.4%). Evidence was found that local isolation of individual sick animals was more effective than whole group isolation and that subclinical infection and undetected circulation may occur on large-scale farms in Saudi Arabia, although both of these points require further evaluation. On the unaffected farm, the mean reciprocal titres for the vaccine and field strains were all above the cut-off supposed to correlate with clinical protection based on evidence from challenge studies. An estimate of vaccination effectiveness was not possible on the affected farms, but the incidence of FMD provides a more realistic estimation of the expected vaccine performance than in vivo studies or r1 value as it is based on field conditions and natural exposure. This study shows that analysis of field data from FMD outbreaks are a useful addition to more conventional challenge and in vitro based evaluations of vaccines and suggests further work is necessary to validate correlates of protection in field conditions.

Kuderna L F K, Tomlinson C, Hillier L W, Tran A, Fiddes I, Armstrong J, Laayouni H, Gordon D, Huddleston J, Perez R G, Povolotskaya I, Armero A S, Garrido J G, Ho D, Ribeca P, Alioto T, Green R E, Paten B, Navarro A, Betranpetit J, Herrero J, Eichler E E, Sharp A J, Feuk L, Warren W C, Marques-Bonet T (2017)

A 3-way hybrid approach to generate a new high quality chimpanzee reference genome (Pan_tro_3.0)

GigaScience 6 (11), 1-6


The chimpanzee is arguably the most important species for the study of human origins. A key resource for these studies is a high quality reference genome assembly, however, as most mammalian genomes, the current iteration of the chimpanzee reference genome assembly it is highly fragmented. In the current iteration of the chimpanzees reference genome assembly (Pan_tro_2.1.4), the sequence is scattered across more then 183,000 contigs and incorporating over 159,000 gaps, with a genome wide contig N50 of 51 Kbp. Findings: In this work we produce an extensive and diverse array of sequencing datasets to rapidly assemble a new chimpanzee reference that surpasses previous iterations in bases represented and organized in large scaffolds. To this end, we show substantial improvements over the current release of the chimpanzee genome (Pan_tro_2.1.4) by several metrics, such as: increased contiguity by >750% and 300% on contigs and scaffolds, respectively; closure of 77% of gaps in the Pan_tro_2.1.4 assembly gaps spanning >850 Kbp of novel coding sequence based on RNASeq data. We furthermore report over 2,700 genes that had putatively erroneous frame-shift predictions to human in Pan_tro_2.1.4 and show a substantial increase in the annotation of repetitive elements. Conclusions: We apply a simple 3-way hybrid approach to considerably improve the reference genome assembly for the chimpanzee, providing a valuable resource to study human origins. We furthermore produced extensive sequencing datasets that are all derived from the same cell line, generating a broad non-human benchmark dataset.

Saduakassova M A, Sultanov A A, Kutumbetov L B, Wadsworth J, Wood B A, Knowles N J, King D P, Bachanek-Bankowska K (2017)

Development and evaluation of a novel real-time RT-PCR to detect foot-and-mouth disease viruses from the emerging A/ASIA/G-VII lineage

Journal of Virological Methods 252, 37-41
Publisher’s version:


A new lineage of foot-and-mouth disease virus (FMDV), called A/ASIA/G-VII, emerged from the Indian subcontinent in 2015 and continues to spread in Western Asia. Currently, the distribution of viruses belonging to this lineage is defined using sequencing approaches, but other cheaper faster diagnostic methods are urgently needed. Thus, this study describes the development and validation of a novel A/ASIA/G-VII lineage-specific real-time RT-PCR (rRT-PCR). Diagnostic sensitivity and specificity were evaluated using representative field specimens and isolates from the A/ASIA/G-VII lineage, as well as samples comprising other FMDV lineages that co-circulate in Asia (n=54). This lineage-specific assay accurately detected all A/ASIA/G-VII samples tested (n=29), and no detection was observed for samples belonging to other FMDV lineages (n=25), namely A/ASIA/Sea-97, A/ASIA/Iran-05SIS-10, A/ASIA/Iran-05FAR-11, Asia1/ASIA/Sindh-08, O/CATHAY, O/ME-SA/PanAsia-2ANT-10, O/ME-SA/Ind-2001d, O/SEA/Mya-98. Additionally, the limit of detection was found to be at least equivalent to a pan-serotypic rRT-PCR assay. Therefore, these data indicate that this newly developed rRT-PCR assay can be applied to characterise field isolates in countries where the A/ASIA/G-VII lineage is endemic, as well as to monitor new incursions and outbreaks due to this lineage.

Sastry M, Zhang B, Chen M, Joyce M G, Kong W-P, Chuang G-Y, Ko K, Kumar A, Silacci C, Thom M, Salazar A M, Corti D, Lanzavecchia A, Taylor G, Mascola J R, Graham B S, Kwong P D (2017)

Adjuvants and the vaccine response to the DS-Cav1-stabilized fusion glycoprotein of respiratory syncytial virus

PLOS ONE 12 (10), e0186854


Appropriate adjuvant selection may be essential to optimize the potency and to tailor the immune response of subunit vaccines. To induce protective responses against respiratory syncytial virus (RSV)—a highly prevalent childhood pathogen without a licensed vaccine—we previously engineered a pre-fusion-stabilized trimeric RSV F (pre-F) “DS-Cav1” immunogen, which induced high titer RSV-neutralizing antibodies, in mice and non-human primates, when formulated with adjuvants Poly (I:C) and Poly (IC:LC), respectively. To assess the impact of different adjuvants, here we formulated RSV F DS-Cav1 with multiple adjuvants and assessed immune responses. Very high RSV-neutralizing antibody responses (19,006 EC50) were observed in naïve mice immunized with 2 doses of DS-Cav1 adjuvanted with Sigma adjuvant system (SAS), an oil-in-water adjuvant, plus Carbopol; high responses (3658–7108) were observed with DS-Cav1 adjuvanted with Alum, SAS alone, Adjuplex, Poly (I:C) and Poly (IC:LC); and moderate responses (1251–2129) were observed with DS-Cav1 adjuvanted with the TLR4 agonist MPLA, Alum plus MPLA or AddaVax. In contrast, DS-Cav1 without adjuvant induced low-level responses (6). A balanced IgG1 and IgG2a (Th2/Th1) immune response was elicited in most of the high to very high response groups (all but Alum and Adjuplex). We also tested the immune response induced by DS-Cav1 in elderly mice with pre-existing DS-Cav1 immunity; we observed that DS-Cav1 adjuvanted with SAS plus Carbopol boosted the response 2-3-fold, whereas DS-Cav1 adjuvanted with alum boosted the response 5-fold. Finally, we tested whether a mixture of ISA 71 VG and Carbopol would enhanced the antibody response in DS-Cav1 immunized calves. While pre-F-stabilized bovine RSV F induced very high titers in mice when adjuvanted with SAS plus Carbopol, the addition of Carbopol to ISA 71 VG did not enhance immune responses in calves. The vaccine response to pre-F-stabilized RSV F is augmented by adjuvant, but the degree of adjuvant-induced enhancement appears to be both context-dependent and species-specific.

Zell R, Delwart E, Gorbalenya A E, Hovi T, King A M Q, Knowles N J, Lindberg A M, Pallansch M A, Palmenberg A C, Reuter G, Simmonds P, Skern T, Stanway G, Yamashita T (2017)

ICTV Virus Taxonomy Profile: Picornaviridae

Journal of General Virology 98 (10), 2421-2422


The family Picornaviridae comprises small non-enveloped viruses with RNA genomes of 6.7 to 10.1 kb, and contains >30 genera and >75 species. Most of the known picornaviruses infect mammals and birds, but some have also been detected in reptiles, amphibians and fish. Many picornaviruses are important human and veterinary pathogens and may cause diseases of the central nervous system, heart, liver, skin, gastrointestinal tract or upper respiratory tract. Most picornaviruses are transmitted by the faecal-oral or respiratory routes. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the taxonomy of the Picornaviridae, which is available at

Riitho V, Walters A A, Somavarapu S, Lamp B, Rümenapf T, Krey T, Rey F A, Oviedo-Orta E, Stewart G R, Locker N, Steinbach F, Graham S P (2017)

Design and evaluation of the immunogenicity and efficacy of a biomimetic particulate formulation of viral antigens

Scientific Reports 7, 13743


Subunit viral vaccines are typically not as efficient as live attenuated or inactivated vaccines at inducing protective immune responses. This paper describes an alternative ‘biomimetic’ technology; whereby viral antigens were formulated around a polymeric shell in a rationally arranged fashion with a surface glycoprotein coated on to the surface and non-structural antigen and adjuvant encapsulated. We evaluated this model using BVDV E2 and NS3 proteins formulated in poly-(D, L-lactic-co-glycolic acid) (PLGA) nanoparticles adjuvanted with polyinosinic:polycytidylic acid (poly(I:C) as an adjuvant (Vaccine-NP). This Vaccine-NP was compared to ovalbumin and poly(I:C) formulated in a similar manner (Control-NP) and a commercial adjuvanted inactivated BVDV vaccine (IAV), all inoculated subcutaneously and boosted prior to BVDV-1 challenge. Significant virus-neutralizing activity, and E2 and NS3 specific antibodies were observed in both Vaccine-NP and IAV groups following the booster immunisation. IFN-? responses were observed in ex vivo PBMC stimulated with E2 and NS3 proteins in both vaccinated groups. We observed that the protection afforded by the particulate vaccine was comparable to the licenced IAV formulation. In conclusion, the biomimetic particulates showed a promising immunogenicity and efficacy profile that may be improved by virtue of being a customisable mode of delivery.

Farhanah M I, Yasmin A R, Mat Isa N, Hair-Bejo M, Ideris A, Powers C, Oladapo O, Nair V, Khoo J-S, Ghazali A-K, Yee W-Y, Omar A R (2017)

Bursal transcriptome profiling of different inbred chicken lines reveals key differentially expressed genes at 3 days post-infection with very virulent infectious bursal disease virus

Journal of General Virology early view,


Infectious bursal disease is a highly contagious disease in the poultry industry and causes immunosuppression in chickens. Genome-wide regulations of immune response genes of inbred chickens with different genetic backgrounds, following very virulent infectious bursal disease virus (vvIBDV) infection are poorly characterized. Therefore, this study aims to analyse the bursal tissue transcriptome of six inbred chicken lines 6, 7, 15, N, O and P following infection with vvIBDV strain UK661 using strand-specific next-generation sequencing, by highlighting important genes and pathways involved in the infected chicken during peak infection at 3?days post-infection. All infected chickens succumbed to the infection without major variations among the different lines. However, based on the viral loads and bursal lesion scoring, lines P and 6 can be considered as the most susceptible lines, while lines 15 and N were regarded as the least affected lines. Transcriptome profiling of the bursa identified 4588 genes to be differentially expressed, with 2985 upregulated and 1642 downregulated genes, in which these genes were commonly or uniquely detected in all or several infected lines. Genes that were upregulated are primarily pro-inflammatory cytokines, chemokines and IFN-related. Various genes that are associated with B-cell functions and genes related to apoptosis were downregulated, together with the genes involved in p53 signalling. In conclusion, bursal transcriptome profiles of different inbred lines showed differential expressions of pro-inflammatory cytokines and chemokines, Th1 cytokines, JAK-STAT signalling genes, MAPK signalling genes, and their related pathways following vvIBDV infection.


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