Publications

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

There were a total of 2599 results for your search.

Abstract

Many infectious pathogens are shared through social interactions, and examining host connectivity has offered valuable insights for understanding patterns of pathogen transmission across wildlife species. African buffalo are social ungulates and important reservoirs of directly-transmitted pathogens that impact numerous wildlife and livestock species. Here, we analyzed African buffalo social networks to quantify variation in close contacts, examined drivers of contact heterogeneity, and investigated how the observed contact patterns affect pathogen invasion likelihoods for a wild social ungulate. We collected continuous association data using proximity collars and sampled host traits approximately every 2 months during a 15-month study period in Kruger National Park, South Africa. Although the observed herd was well connected, with most individuals contacting each other during each bimonthly interval, our analyses revealed striking heterogeneity in close-contact associations among herd members. Network analysis showed that individual connectivity was stable over time and that individual age, sex, reproductive status, and pairwise genetic relatedness were important predictors of buffalo connectivity. Calves were the most connected members of the herd, and adult males were the least connected. These findings highlight the role susceptible calves may play in the transmission of pathogens within the herd. We also demonstrate that, at time scales relevant to infectious pathogens found in nature, the observed level of connectivity affects pathogen invasion likelihoods for a wide range of infectious periods and transmissibilities. Ultimately, our study identifies key predictors of social connectivity in a social ungulate and illustrates how contact heterogeneity, even within a highly connected herd, can shape pathogen invasion likelihoods.

Abstract

Viruses emerging from wildlife can cause outbreaks in humans and domesticated animals. Predicting the emergence of future pathogens and mitigating their impacts requires an understanding of what shapes virus diversity and dynamics in wildlife reservoirs. In order to better understand coronavirus ecology in wild species, we sampled birds within a coastal freshwater lagoon habitat across 5 years, focussing on a large population of mute swans (Cygnus olor) and the diverse species that they interact with. We discovered and characterised the full genome of a divergent gammacoronavirus belonging to the Goose coronavirus CB17 species. We investigated the genetic diversity and dynamics of this gammacoronavirus using untargeted metagenomic sequencing of 223 faecal samples from swans of known age and sex, and RT-PCR screening of 1632 additional bird samples. The virus circulated persistently within the bird community; virus prevalence in mute swans exhibited seasonal variations, but did not change with swan age-class or epidemiological year. One whole genome was fully characterised, and revealed that the virus originated from a recombination event involving an undescribed gammacoronavirus species. Multiple lineages of this gammacoronavirus co-circulated within our study population. Viruses from this species have recently been detected in aquatic birds from both the Anatidae and Rallidae families, implying that host species habitat sharing may be important in shaping virus host range. As the host range of the Goose coronavirus CB17 species is not limited to geese, we propose that this species name should be updated to 'Waterbird gammacoronavirus 1'. Non-invasive sampling of bird coronaviruses may provide a tractable model system for understanding the evolutionary and cross-species dynamics of coronaviruses.

Abstract

A novel liquid stabiliser was tested with the Nigeria 75/1 Peste des Petit Ruminants (PPR) vaccine over two field studies carried out in sheep and goats. PPR seronegative sheep and goats were selected from farms surrounding Amman, Jordan and were vaccinated with either a stabilised liquid PPR vaccine that had been formulated 3 months prior to use and stored at 2-8 °C or a reconstituted lyophilised PPRV vaccine reconstituted on the day of vaccination. Sera were taken immediately before vaccination and at approximately 1.5, 3 and 6 months following vaccination, then subsequently tested using IDVet ID Screen® PPR competition ELISA and Serum Neutralisation tests to determine the presence of PPRV anti-N antibodies and neutralising antibodies, respectively. It was observed that the liquid-stabilised vaccine was able to provide comparable antibody responses in both species to those induced by the lyophilized vaccine. The ability to store liquid stabilised PPRV vaccine for field use would positively impact PPRV eradication efforts.

Abstract

High pathogenicity avian influenza (HPAI) H5N1 is a subtype of the influenza A virus primarily found in birds. The subtype emerged in China in 1996 and has spread globally, causing significant morbidity and mortality in birds and humans. In Cambodia, a lethal case was reported in February 2023 involving an 11-year-old girl, marking the first human HPAI H5N1 infection in the country since 2014. This research examined the zoonotic potential of the human H5N1 isolate, A/Cambodia/NPH230032/2023 (KHM/23), by assessing its receptor binding, fusion pH, HA thermal stability, and antigenicity. Results showed that KHM/23 exhibits similar receptor binding and antigenicity as the early clade 2.3.2.1c HPAI H5N1 strain, and it does not bind to human-like receptors. Despite showing limited zoonotic risk, the increased thermal stability and reduced pH of fusion in KHM/23 indicate a potential threat to poultry, emphasizing the need for vigilant monitoring.

de Brito RCF, Holtham K, Roser J, Saunders JE, Wezel Y, Henderson S, Mauch T, Sanz-Bernardo B, Frossard J-P, Bernard M, Lean FZX, Nunez A, Gubbins S, Sua´rez NM, Davison AJ, Francis MJ, Huether M, Benchaoui H, Salt J, Fowler VL, Jarvis MA, Graham SP (2023)

An attenuated herpesvirus vectored vaccine candidate induces T-cell responses against highly conserved porcine reproductive and respiratory syndrome virus M and NSP5 proteins that are unable to control infection

Frontiers in Immunology 14, 1201973

Abstract

Porcine reproductive and respiratory syndrome virus (PRRSV) remains a leading cause of economic loss in pig farming worldwide. Existing commercial vaccines, all based on modified live or inactivated PRRSV, fail to provide effective immunity against the highly diverse circulating strains of both PRRSV-1 and PRRSV-2. Therefore, there is an urgent need to develop more effective and broadly active PRRSV vaccines. In the absence of neutralizing antibodies, T cells are thought to play a central role in controlling PRRSV infection. Herpesvirus-based vectors are novel vaccine platforms capable of inducing high levels of T cells against encoded heterologous antigens. Therefore, the aim of this study was to assess the immunogenicity and efficacy of an attenuated herpesvirus-based vector (bovine herpesvirus-4; BoHV-4) expressing a fusion protein comprising two well-characterized PRRSV-1 T-cell antigens (M and NSP5). Prime-boost immunization of pigs with BoHV-4 expressing the M and NSP5 fusion protein (vector designated BoHV-4-M-NSP5) induced strong IFN-γ responses, as assessed by ELISpot assays of peripheral blood mononuclear cells (PBMC) stimulated with a pool of peptides representing PRRSV-1 M and NSP5. The responses were closely mirrored by spontaneous IFN-γ release from unstimulated cells, albeit at lower levels. A lower frequency of M and NSP5 specific IFN-γ responding cells was induced following a single dose of BoHV-4-M-NSP5 vector. Restimulation using M and NSP5 peptides from PRRSV-2 demonstrated a high level of cross-reactivity. Vaccination with BoHV-4-M-NSP5 did not affect viral loads in either the blood or lungs following challenge with the two heterologous PRRSV-1 strains. However, the BoHV-4-M-NSP5 prime-boost vaccination showed a marked trend toward reduced lung pathology following PRRSV-1 challenge. The limited effect of T cells on PRRSV-1 viral load was further examined by analyzing local and circulating T-cell responses using intracellular cytokine staining and proliferation assays. The results from this study suggest that vaccine-primed T-cell responses may have helped in the control of PRRSV-1 associated tissue damage, but had a minimal, if any, effect on controlling PRRSV-1 viral loads. Together, these results indicate that future efforts to develop effective PRRSV vaccines should focus on achieving a balanced T-cell and antibody response.

Abstract

Mycobacterium bovis, the causative agent of bovine tuberculosis (bTB), is a globally prevalent pathogen with significant animal welfare, economic and public health impacts. In the UK, the control of bTB relies on detection via tuberculin skin tests with ancillary interferon gamma (IFN-γ) release assays, followed by culling infected animals. Vaccination with Bacille Calmette–Guérin (BCG) could be an important element of bTB control, and a number of studies have demonstrated its protective efficacy, particularly when young calves are vaccinated. Here, we compared immune responses and the protective efficacy of BCG in calves vaccinated within the first day of life and at three weeks of age. Significant protection from M. bovis infection was observed in BCG-vaccinated calves compared to non-vaccinated, age-matched controls. No significant differences were shown between calves vaccinated at one day and at three weeks of age when assessing the protective efficacy of BCG (measured as a reduction in lesions and bacterial burden). Antigen-specific IFN-γ levels were similar between the BCG-vaccinated groups, but significantly different from the non-vaccinated control animals. Antigen-specific IFN-γ expression post-BCG vaccination was correlated significantly with protection from M. bovis infection, whereas IFN-γ levels post-challenge correlated with pathology and bacterial burden. These results indicate that early-life vaccination with BCG could have a significant impact on M. bovis infection and, therefore, bTB incidence, and they demonstrate that age, at least within the first month of life, does not significantly impact the protective effect of vaccination.

Abstract

Chronic wounds and their treatment present a significant burden to patients and healthcare systems alike, with their management further complicated by bacterial infection. Historically, antibiotics have been deployed to prevent and treat infections, but the emergence of bacterial antimicrobial resistance and the frequent development of biofilms within the wound area necessitates the identification of novel treatment strategies for use within infected chronic wounds. Here, several non-antibiotic compounds, polyhexamethylene biguanide (PHMB), curcumin, retinol, polysorbate 40, ethanol, and D-α-tocopheryl polyethylene glycol succinate 1000 (TPGS) were screened for their antibacterial and antibiofilm capabilities. The minimum inhibitory concentration (MIC) and crystal violet (CV) biofilm clearance against two bacteria frequently associated with infected chronic wounds, Staphylococcus aureus and Pseudomonas aeruginosa, were determined. PHMB was observed to have highly effective antibacterial activity against both bacteria, but its ability to disperse biofilms at MIC levels was variable. Meanwhile, TPGS had limited inhibitory activity but demonstrated potent antibiofilm properties. The subsequent combination of these two compounds in a formulation resulted in a synergistic enhancement of their capability to kill both S. aureus and P. aeruginosa and disperse their biofilms. Collectively, this work highlights the utility of combinatory approaches to the treatment of infected chronic wounds where bacterial colonization and biofilm formation remains significant issues.

Abstract

Emerging arboviruses such as chikungunya and Zika viruses have unexpectedly caused widespread outbreaks in tropical and subtropical regions recently. Ross River virus (RRV) is endemic in Australia and has epidemic potential. In Malaysia, Aedes mosquitoes are abundant and drive dengue and chikungunya outbreaks. We assessed risk of an RRV outbreak in Kuala Lumpur, Malaysia by determining vector competence of local Aedes mosquitoes and local seroprevalence as a proxy of human population susceptibility.

Chrun, T, Maze, EA, Roper, KJ, Vatzia, E, Paudyal, B, McNee, A, Martini, V, Manjegowda, T, Freimanis, G, Silesian, A, Polo, N, Clark, B, Besell, E, Booth, G, Carr, BV, Edmans, M, Nunez, A, Koonpaew, S, Wanasen, N, Graham, SP, Tchilian, E (2023)

Simultaneous co-infection with swine influenza A and porcine reproductive and respiratory syndrome viruses potentiates adaptive immune responses

Frontiers in Immunology 14, 1192604

Abstract

Porcine respiratory disease is multifactorial and most commonly involves pathogen co-infections. Major contributors include swine influenza A (swIAV) and porcine reproductive and respiratory syndrome (PRRSV) viruses. Experimental co-infection studies with these two viruses have shown that clinical outcomes can be exacerbated, but how innate and adaptive immune responses contribute to pathogenesis and pathogen control has not been thoroughly evaluated. We investigated immune responses following experimental simultaneous co-infection of pigs with swIAV H3N2 and PRRSV-2. Our results indicated that clinical disease was not significantly exacerbated, and swIAV H3N2 viral load was reduced in the lung of the co-infected animals. PRRSV-2/swIAV H3N2 co-infection did not impair the development of virus-specific adaptive immune responses. swIAV H3N2-specific IgG serum titers and PRRSV-2-specific CD8β+ T-cell responses in blood were enhanced. Higher proportions of polyfunctional CD8β+ T-cell subset in both blood and lung washes were found in PRRSV-2/swIAV H3N2 co-infected animals compared to the single-infected groups. Our findings provide evidence that systemic and local host immune responses are not negatively affected by simultaneous swIAV H3N2/PRRSV-2 co-infection, raising questions as to the mechanisms involved in disease modulation.

Ulziibat, G, Raizman, E, Lkhagvasuren, A, Bartels, CJM, Oyun-Erdene, O, Khishgee, B, Browning, C, King, DP, Ludi, AB, Lyons, NA (2023)

Comparison of vaccination schedules for foot-and-mouth disease among cattle and sheep in Mongolia

Frontiers in Veterinary Science 10, 990043

Abstract

Vaccines are a critical tool for the control strategy for foot-and-mouth disease (FMD) in Mongolia where sporadic outbreaks regularly occur. A two-dose primary vaccination course is recommended for most commercial vaccines though this can be logistically challenging to deliver among nomadic pastoralist systems which predominate in the country. Although there is evidence that very high potency vaccines can provide prolonged duration of immunity, this has not been demonstrated under field conditions using commercially available vaccines. This study compared neutralizing titres to a O/ME-SA/Panasia strain over a 6-month period following either a two-dose primary course or a single double-dose vaccination among Mongolian sheep and cattle using a 6.0 PD50 vaccine. Titers were not significantly different between groups except in sheep at six-months post vaccination when the single double-dose group had significantly lower titers. These results indicate the single double-dose regimen may be a cost-effective approach for vaccination campaigns supporting FMD control in Mongolia.

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