Publications by authors named "Tom N Mcneilly"

Introduction: We previously demonstrated efficacy of an 8-antigen recombinant subunit vaccine against a single species homologous challenge in lambs and in lambing ewes in pen trials. We subsequently demonstrated efficacy of a simplified, 2-antigen, version of this vaccine in lambs in pen trials. Here, we test both vaccines in lambing ewes in a field setting.

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Atypical porcine pestivirus (APPV) is a novel member of the Pestivirus genus detected in association with congenital tremor (CT) type A-II outbreaks and from apparently healthy pigs, both as singular infection and as part of multi-pathogen infections. 'Classical' pestiviruses are known to cause immunosuppression of their host, which can increase susceptibility to secondary infections, severely impacting health, welfare, and production. To investigate APPV's effect on the host's immune system and characterise disease outcomes, 12 piglets from a natural APPV CT type A-II outbreak were experimentally infected with porcine reproductive and respiratory syndrome virus (PRRSV), a significant porcine pathogen.

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The rectal-anal junction (RAJ) is the major colonization site of Shiga toxin-producing Escherichia coli (STEC) O157 in beef cattle, leading to transmission of this foodborne pathogen from farms to food chains. To date, there is limited understanding regarding whether the mucosa-attached microbiome has a profound impact on host-STEC interactions. In this study, the active RAJ mucosa-attached microbiota and its potential role in host immunity-STEC commensal interactions were investigated using RAJ mucosal biopsies collected from calves orally challenged with two STEC O157 strains with or without functional stx2a (stx2a+ or stx2a-).

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Organisms have evolved diverse strategies to manage parasite infections. Broadly, hosts may avoid infection by altering behaviour, resist infection by targeting parasites or tolerate infection by repairing associated damage. The effectiveness of a strategy depends on interactions between, for example, resource availability, parasite traits (virulence, life-history) and the host itself (nutritional status, immunopathology).

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Upon parasitic helminth infection, activated intestinal tuft cells secrete interleukin-25 (IL-25), which initiates a type 2 immune response during which lamina propria type 2 innate lymphoid cells (ILC2s) produce IL-13. This causes epithelial remodeling, including tuft cell hyperplasia, the function of which is unknown. We identified a cholinergic effector function of tuft cells, which are the only epithelial cells that expressed choline acetyltransferase (ChAT).

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Article Synopsis
  • Telomere length (TL) is thought to indicate the physiological costs of reproduction, infection, and immune responses, but its relationships with these factors in natural populations are underexplored.
  • A study on free-living Soay sheep found that higher helminth parasite burdens were associated with longer leucocyte TL, challenging the idea that short TL indicates high infection costs.
  • The research revealed no significant link between TL and immune response markers, suggesting TL does not effectively represent the costs of infection or immunity in wild animals.
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Previous vaccination trials have demonstrated that thiol proteins affinity purified from Ostertagia ostertagi excretory-secretory products (O. ostertagi ES-thiol) are protective against homologous challenge. Here we have shown that protection induced by this vaccine was consistent across four independent vaccine-challenge experiments.

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  • Q fever is a zoonotic disease caused by a bacterial pathogen primarily found in livestock like sheep and goats, which are major reservoirs for human infection.
  • Current vaccines are based on formalin-inactivated bacterins but have limitations due to reactogenicity and interference with diagnostic tests.
  • This study mapped antibody responses from various species to identify over 493 potential protein antigens, paving the way for improved vaccines and diagnostic methods for Q fever.
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Tuft cells have recently emerged as the focus of intense interest following the discovery of their chemosensory role in the intestinal tract, and their ability to activate Type 2 immune responses to helminth parasites. Moreover, they populate a wide range of mucosal tissues and are intimately connected to immune and neuronal cells, either directly or through the release of pharmacologically active mediators. They are now recognised to fulfil both homeostatic roles, in metabolism and tissue integrity, as well as acting as the first sensors of parasite infection, immunity to which is lost in their absence.

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This work discusses and demonstrates the novel use of multivariate analysis and data dimensionality reduction techniques to handle the variety and complexity of data generated in efficacy trials for the development of a prototype vaccine to protect sheep against the Teladorsagia circumcincta nematode. A curated collection of data dimension reduction and visualisation techniques, in conjunction with sensible statistical modelling and testing which explicitly model key features of the data, offers a synthetic view of the relationships between the multiple biological parameters measured. New biological insight is gained into the patterns and associations involving antigen-specific antibody levels, antibody avidity and parasitological parameters of efficacy that is not achievable by standard statistical practice in the field.

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  • Shiga toxin-producing E. coli (STEC) infections from wildlife are on the rise, with a notable instance in Scotland linked to venison in 2015 revealing gaps in knowledge about these pathogens.
  • A nationwide survey in Scotland found a low prevalence of STEC O157 in wild deer at 0.28%, but the bacteria were still found in high quantities in their feces and showed strong potential to cause human illness.
  • A follow-up investigation suggested that one particular wild deer sample may have contributed to a human outbreak in 2017, underscoring the need for strict food safety measures when handling venison.
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  • Over the past 20 years, the frequency of human infections caused by the E. coli strain O157 has been 2.5 times higher in Scotland compared to England and Wales.
  • A study combining cattle survey data and human clinical cases from 2014-2015 found that certain strains of O157 are more prevalent in Scottish cattle and humans, particularly the Stx2a+ strain PT21/28.
  • Whole genome sequencing revealed that most O157 diversity in human cases stemmed from cattle, with significant strain differences indicating localized transmission within Scotland.
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Article Synopsis
  • * It investigates a novel adjuvant system called calcium phosphate-coated microcrystals (CaP-PCMCs) that enhances specific antibody responses in vaccines, particularly in animal models.
  • * The research reveals that CaP-PCMCs induce a specific type of cell death (pyroptosis) in certain immune cells, which may help explain how these microcrystals work to enhance vaccine effectiveness.
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Teladorsagia circumcincta is an abomasal parasitic nematode that can cause serious issues in small ruminant production, which are aggravated by drug resistance. Vaccines have been suggested as a feasible, long-lasting alternative for control since adaptation to the host's immune mechanisms by helminths develops at a much slower pace than anthelmintic resistance. Recently, a T.

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The bacterium can cause the disease Q-fever in a wide range of animal hosts. Ruminants, including sheep, are thought to play a pivotal role in the transmission of to humans; however, the only existing livestock vaccine, namely, Coxevac (Ceva Animal Health Ltd., Libourne, France), a killed bacterin vaccine based on phase I strain Nine-Mile, is only approved for use in goats and cattle.

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Article Synopsis
  • Understanding how parasites survive and affect host immune responses is key for improving disease management and developing new treatments.
  • Traditional methods like microarray and RNA sequencing give insights into gene expression during parasite development but miss details about different cell types and their organization.
  • Single-cell RNA sequencing (scRNA-seq) provides a deeper look at gene expression in individual cells and can be complemented by using organoids to study host-parasite interactions and parasite growth in a lab setting.
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The increasing resistance to anthelmintics has necessitated the exploration of alternative control strategies of gastrointestinal nematode (GIN) infections. A sustainable option is genetic selection based on differences in susceptibility to GIN infection between and within breeds of sheep. Here, three-month-old Canaria Hair breed (GIN-resistant) and Canaria Sheep breed (GIN-susceptible) showed no significant between-breed differences after trickle infection with , whereas considerable individual variability was found in both breeds.

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Trade-offs between host resistance to parasites and host growth or reproduction can occur due to allocation of limited available resources between competing demands. To predict potential trade-offs arising from genetic selection for host resistance, a better understanding of the associated nutritional costs is required. Here, we studied resistance costs by using sheep from lines divergently selected on their resistance to a common blood-feeding gastro-intestinal parasite ().

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Wild deer hunting is necessary in Scotland to control deer population density, with most carcasses being processed for human consumption. As limited information is available on the microbial condition of Scottish venison, we studied the variation of total coliforms and Escherichia coli (E. coli) on 214 wild deer carcasses collected from six approved establishments.

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  • Long-term ecological studies are crucial for understanding the impact of parasites on host organisms, revealing how infection prevalence and abundance change over time.
  • A 31-year study on wild Soay sheep in St. Kilda showed an increase in the prevalence of gastrointestinal parasites, particularly strongyle nematodes and coccidia, which affected different age groups differently.
  • The study found that host population density influenced parasite transmission significantly, but the temporal changes in parasite abundance varied independently of this density and highlighted notable trends, especially in lambs.
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Article Synopsis
  • - Gastro-intestinal nematode (GIN) parasites in cattle lead to significant production losses, prompting a need for effective control methods due to increasing resistance to standard anthelmintic drugs.
  • - Researchers developed bovine gastric epithelial organoids from abomasal tissue to better study the interactions between hosts and GINs, which has been challenging with existing models.
  • - The study found that these organoids accurately represent bovine gastric tissue and can effectively model parasite invasion, showcasing a "ballooning" reaction to both the parasites and their secretions, highlighting their potential for future research and intervention methods.
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Individuals vary broadly in their response to vaccination and subsequent challenge infection, with poor vaccine responders causing persistence of both infection and transmission in populations. Yet despite having substantial economic and societal impact, the immune mechanisms that underlie such variability, especially in infected tissues, remain poorly understood. Here, to characterise how antihelminthic immunity at the mucosal site of infection developed in vaccinated lambs, we inserted gastric cannulae into the abomasa of three-month- and six-month-old lambs and longitudinally analysed their local immune response during subsequent challenge infection.

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Gastrointestinal nematode (GIN) infections are a serious drawback on small ruminant production. Since anthelmintic resistance has extended, optimisation of alternative non-chemical control strategies has attracted interest. Recently, a prototype recombinant vaccine protected immunologically mature sheep from Texel-cross and Canaria Sheep breeds against Teladorsagia circumcincta.

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