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Cognition and behavior in sheep repetitively inoculated with aluminum adjuvant-containing vaccines or aluminum adjuvant only

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Abstract

Aluminum (Al)-containing vaccines are common in sheep management and they have been associated with the Autoimmune/inflammatory Syndrome Induced by Adjuvants (ASIA syndrome). The aim of this study was to investigate cognitive and behavioral changes in sheep subjected to a protocol of repetitive inoculation with Al-containing products. Twenty-one lambs were assigned to three groups (n = 7 each): A (Control), B (Adjuvant-only), C (Vaccine). Group C was inoculated with commercial Al-containing vaccines; Group B received the equivalent dose of Al only (Alhydrogel®) and Group A received PBS. Sixteen inoculations were administered within a 349-day period. Ethologic changes were studied in late summer (7 inoculations) and mid-winter (16 inoculations). Animals in groups B and C exhibited behavioral changes: affiliative interactions were significantly reduced and aggressive interactions and stereotypies increased significantly. They also exhibited a significant increase in excitatory behavior and compulsive eating. In general, changes were more pronounced in the Vaccine group than they were in the Adjuvant-only group. Some changes were already significant in summer, after seven inoculations only. This study is the first to describe behavioral changes in sheep after having received repetitive injections of Al-containing products, explaining some of the clinical signs observed in ovine ASIA syndrome.

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... At the end of 2018, the same researchers published a study [23] a study describing behavioral changes in sheep after having Thimerosal is 49.55% percent ethylmercury by weight and is an organic mercury compound with toxicity comparable to methylmercury [25] but ethylmercury is far more toxic to and persistent in the brain, where it has a propensity to accumulate as inorganic mercury [26], with an estimated half-life of as long as twenty-seven years [27]. ...
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Aluminium (Al) oxyhydroxide (Alhydrogel®), the main adjuvant licensed for human and animal vaccines, consists of primary nanoparticles that spontaneously agglomerate. Concerns about its safety emerged following recognition of its unexpectedly long-lasting biopersistence within immune cells in some individuals, and reports of chronic fatigue syndrome, cognitive dysfunction, myalgia, dysautonomia and autoimmune/inflammatory features temporally linked to multiple Al-containing vaccine administrations. Mouse experiments have documented its capture and slow transportation by monocyte-lineage cells from the injected muscle to lymphoid organs and eventually the brain. The present study aimed at evaluating mouse brain function and Al concentration 180 days after injection of various doses of Alhydrogel® (200, 400 and 800 μg Al/kg of body weight) in the tibialis anterior muscle in adult female CD1 mice. Cognitive and motor performances were assessed by 8 validated tests, microglial activation by Iba-1 immunohistochemistry, and Al level by graphite furnace atomic absorption spectroscopy.
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Metals are frequently used in industry and represent a major source of toxin exposure for workers. For this reason governmental agencies regulate the amount of metal exposure permissible for worker safety. While essential metals serve physiologic roles, metals pose significant health risks upon acute and chronic exposure to high levels. The central nervous system is particularly vulnerable to metals. The brain readily accumulates metals, which under physiologic conditions are incorporated into essential metalloproteins required for neuronal health and energy homeostasis. Severe consequences can arise from circumstances of excess essential metals or exposure to toxic nonessential metal. Herein, we discuss sources of occupational metal exposure, metal homeostasis in the human body, susceptibility of the nervous system to metals, detoxification, detection of metals in biologic samples, and chelation therapeutic strategies. The neurologic pathology and physiology following aluminum, arsenic, lead, manganese, mercury, and trimethyltin exposures are highlighted as classic examples of metal-induced neurotoxicity.
Article
Concerns regarding vaccine safety have emerged following reports of potential adverse events in both humans and animals. In the present study, alum, alum-containing vaccine and alum adjuvant tagged with fluorescent nanodiamonds were used to evaluate i) the persistence time at the injection site, ii) the translocation of alum from the injection site to lymphoid organs, and iii) the behavior of adult CD1 mice following intramuscular injection of alum (400 μg Al/kg). Results showed for the first time a strikingly delayed systemic translocation of adju-vant particles. Alum-induced granuloma remained for a very long time in the injected muscle despite progressive shrinkage from day 45 to day 270. Concomitantly, a markedly delayed translocation of alum to the draining lymph nodes, major at day 270 endpoint, was observed. Translocation to the spleen was similarly delayed (highest number of particles at day 270). In contrast to C57BL/6J mice, no brain translocation of alum was observed by day 270 in CD1 mice. Consistently neither increase of Al cerebral content, nor behavioral changes were observed. On the basis of previous reports showing alum neurotoxic effects in CD1 mice, an additional experiment was done, and showed early brain translocation at day 45 of alum injected subcutaneously at 200 μg Al/kg. This study confirms the striking biopersistence of alum. It points out an unexpectedly delayed diffusion of the adjuvant in lymph nodes and spleen of CD1 mice, and suggests the importance of mouse strain, route of administration, and doses, for future studies focusing on the potential toxic effects of aluminum-based adjuvants.
Article
Development and implementation of health management plans is the cornerstone of profitable farms; prevention of microbial diseases by means of vaccination is an integral part of such a plan. In every production type and management system in small ruminants, microbial diseases have a major significance, hence their proper control must be based in good health management practices, including use of effective and safe vaccines. Development of various types of vaccines is evolving very quickly in recent years and the improvement of new type of vaccines offers prospects. The article reviews and discusses vaccination programs and latest advances in development of vaccines against diseases that cause major economic losses in small ruminants. Specifically, vaccination schedules for the following diseases are reviewed: bacterial abortion (abortion associated with Brucella melitensis, Campylobacter spp., Chlamydophila abortus, Coxiella burnetii, Salmonella abortus ovis or Salmonella brandenburg), caseous lymphadenitis, clostridial diseases, colibacillosis, contagious echtyma, epididymitis caused by Brucella ovis, footrot, mammary diseases (contagious agalactia, mastitis), paratuberculosis and respiratory diseases (respiratory disease caused by Mannheimia haemolytica or other Pasteurellaceae). Copyright © 2015 Elsevier B.V. All rights reserved.
Article
Postweaning management strategies that include an element of social enrichment may reduce weaning stress and improve welfare and productive performance. We analyzed the effect of postweaning handling strategies on welfare and production traits in lambs. After weaning, 36 lambs were assigned to 3 experimental groups with 12 lambs each (control [C], fattening with gentle human female contact [H], and fattening with 2 adult ewes [E]). The average daily gain (ADG) was estimated. Blood samples were taken, and infrared thermography was used to estimate stress variables. There were significant differences among treatments (in favor of alternative strategies) regarding production and stress variables (cortisol, glucose, and creatine kinase). The results suggest that the lambs handled gently during the fattening were less reactive and better able to modulate their physiological stress. The E group adapted better to acute stress than the C group but was less efficient in modulating chronic stress. Both treatments showed higher slaughter live weights and better ADGs compared with the control. The use of social enrichment at weaning, especially to establish a positive human-nonhuman animal bond, alleviates lamb weaning stress and improves welfare and performance.
Article
Abstract In line with an increasing emphasis on promoting positive welfare states in animals, this review extends previous accounts of how recent affective neuroscience observations may be used to identify and then to encourage animals to engage in reward-motivated behaviours. The terms affective states or affects are used to mean the subjective experiences, feelings or emotions that may motivate animals to behave in goal-directed ways and which may accompany success or failure to achieve those goals. These motivational affects may be positive, experienced as rewarding or pleasurable, or negative, experienced as aversive or punishing. There are two overall types: homeostasis-related negative affects that reflect an animal's internal physiological state, and situation-related positive or negative affects that reflect an animal's perception of its external circumstances. The major emphasis is on positive situation-related affects, in particular those that are potentially associated with exploration, feeding and animal-to-animal affiliative behaviours. The review introduces the new concept of positive affective engagement which represents the experience animals may have when they actively respond to motivations to engage in rewarding behaviours, and it incorporates all associated affects that are positive. For example, it would represent a state of engaged aliveness that may attend an animal's goal-directed, energised exploration of and interactions with a stimulus-rich environment. It also represents some states of equally energised, highly focused predatory stalking by carnivores or the focused and engaged foraging by herbivores when they are grazing in natural environments where food sources are abundant. Positive affective engagement may also be anticipated to accompany some aspects of reciprocated affiliative interactions between animals, the dedicated maternal nurturing and care of young, the joyfulness of rough-and-tumble play, and the eroticism and orgasmic pleasures of sexual activity. It is argued that highlighting the genetically pre-programmed, affectively positive impulses to engage in reward motivated activities such as these, and the positive affects that may attend different facets of the process, draws attention to a wider spectrum of welfare enhancing experiences than has hitherto been considered to be important to animals. These neuroscience-supported observations strengthen many prior inferences made from predominantly behaviour-based investigations of animals' preferences, aversions and priorities, the associated development of successful environmental enrichments and the inclusion of these, where practicable, in more recent codes of practice or welfare.
Article
Vaccination has made an enormous contribution to global health. Two major infections, smallpox and rinderpest, have been eradicated. Global coverage of vaccination against many important infectious diseases of childhood has been enhanced dramatically since the creation of WHO's Expanded Programme of Immunization in 1974 and of the Global Alliance for Vaccination and Immunization in 2000. Polio has almost been eradicated and success in controlling measles makes this infection another potential target for eradication. Despite these successes, approximately 6.6 million children still die each year and about a half of these deaths are caused by infections, including pneumonia and diarrhoea, which could be prevented by vaccination. Enhanced deployment of recently developed pneumococcal conjugate and rotavirus vaccines should, therefore, result in a further decline in childhood mortality. Development of vaccines against more complex infections, such as malaria, tuberculosis and HIV, has been challenging and achievements so far have been modest. Final success against these infections may require combination vaccinations, each component stimulating a different arm of the immune system. In the longer term, vaccines are likely to be used to prevent or modulate the course of some non-infectious diseases. Progress has already been made with therapeutic cancer vaccines and future potential targets include addiction, diabetes, hypertension and Alzheimer's disease.
Article
The foraging behavior of eight sheep and 11 goats was studied using a T-maze. In the first experiment, animals were given two free choices in the maze. In each case, the selection of either arm would result in their obtaining high quality food—a situation classified as a ‘win’. Animals of both species tended to return to the originally chosen arm on the second choice, an apparent win-stay strategy. This expression of a win-stay strategy could be attributed to the fact that the animals simply showed a strong lateral preference (handedness). A losing possibility was added in Experiment 2 by introducing low quality food into one arm of the maze. Goats responded by increasing the frequency of shifting on the second free choice, particularly when the first choice was a losing one. Sheep did not respond to this possibility with a measurable change in behavior. Results suggest that foraging behavior may be more strongly influenced by negative or losing experiences than by winning ones, and that effects of losing need to be better incorporated into foraging theory.
Article
The aim of this study was: (1) to design a series of tests to measure fear reactions of domestic sheep placed in different fear-inducing situations; (2) to interpret the observed behaviour in terms of the presence or absence of fear; (3) to test the hypothesis that fear is a unitary phenomenon; (4) to investigate the effects of breed and rearing conditions before weaning as possible factors causing variation in fear reactions.Four tests, based on the presence of stimuli classically reported to induce fear, were designed to measure fear reactions. They involved: (1) a surprise effect; (2) the presence of a human; (3) the presence of a novel object; (4) an unfamiliar environment (open-field test). In each of these tests food was present, so a conflict between food-motivation and fear arose.Eighty-eight sheep were individually submitted to the first three tests on subsequent afternoons having been exposed to the control situation (same surroundings without the fear-inducing stimulus) each morning. The open-field test was conducted on the fifth day.The behaviour of sheep was observed when in control or frightening situations. The results indicate that high values for the following parameters reflect the expression of fear: latency to enter the testroom, latency to feeding, time spent away from the stimulus, immobilization, high-pitch bleats, defecation, locomotory activity (number of squares entered), attempts to escape, trotting, glances at the stimulus and latency to sniff the stimulus. On the other hand high values for feeding time, latency to bleat for the first time, sniffings of the trough and sniffings of the stimulus are expressions of a low level or an absence of fear.The correlations between measurements of fear from different fear-inducing situations suggest that fear is a unitary phenomenon. Fear reactions were influenced by; (a) breed—Romanov sheep were more fearful than Ile-de-France sheep; (b) rearing conditions before weaning—for Romanov but not Ile-de-France sheep, dam-reared animals were more fearful than artificially reared ones.
Article
Wool biting is a behaviour that can develop in housed sheep, in which sheep start to bite and eat the wool of others. The aim of this study was to determine whether (i)supplementing the diet of housed sheep with fibre and (ii) increasing feeding frequency would help to reduce wool biting, aggressive behaviours and wool damage. In a 2 x 2 factorial experiment, 40 Merino wethers were either fed with lucerne-based pellets only, or with pellets supplemented with barley straw. They received their pellets either on a low feeding frequency basis (once a day Monday to Friday mornings, double ration on Friday afternoon, nothing Saturdays and Sundays), or on a high feeding frequency basis (twice a day, every day). The sheep were housed in 4 treatment pens, each with 10 animals. Wool biting and aggressive behaviours were recorded through direct observation and the sheep were scored for wool damage twice a week during the 15-week study. The provision of fibre had a significant effect on reducing wool biting (P < 0.001) and wool damage score (P < 0.001). There was no consistent effect of feeding frequency on wool biting or wool damage, and no fibre x feeding frequency interactions. Whereas wool biting in general increased with time during the study (P < 0.001), levels of aggressive behaviour showed no consistent time trend, and there were no effects of fibre or feeding frequency treatments. It is concluded that wool biting is largely a redirected behaviour in concentrate-fed housed sheep deprived of adequate levels of activity or oral stimulus, and that the provision of roughage will reduce the development of wool biting and improve animal welfare in housed experimental sheep.
Article
The synchronisation of eating, ruminating and idling activity of non-lactating ewes grazing either grass or clover swards was studied. Synchronisation was defined as the proportion of the number of pairs of sheep engaged in a common activity to the total possible number of pairs and was compared to the random expectation using a kappa statistic. Ewes on both swards showed significantly non-random synchronisation of activities. Overall proportion of synchronisation was greater for clover than grass (0.703 vs. 0.554) but synchronisation of eating was less (0.130 vs. 0.223). Bouts of eating were more synchronised at the start than at the end. It is concluded that, wherever possible, individual animals should not be treated as replicates in grazing experiments.
Article
Describes the controversy over the merits of behavioral vs physiological indicators of animal welfare. The debate is illustrated with behavioral and physiological responses of pigs. Pigs respond to stress with an increase in adrenocortical activity; aggression; and abnormal behaviors such as bar biting, sham chewing, and head weaving, called stereotypies (STs). Causes and functions of STs are unclear, but STs may be regarded as a mechanism that helps animals cope with environmental change. Data from research on housing systems for pigs and the human–animal relationship will help in the evaluation of animal welfare. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Article
Stereotypies often develop in environments that independent evidence shows cause poor welfare. Thus the development od stereotypies indicates that well-being has probably been poor, with the animal motivated to show a behaviour pattern that it could not perform normally or to completion. The continued performance of stereotypies may also indicate current suffering. However, an individual or population's degree of stereotypy does not necessarily correspond to the degree to which its well-being or welfare is impaired. This would require individual differences in stereotypy level to be the product of motivational differences and nothing else. In fact, they are also likely to be influenced by an animal's tendency to respond to the eliciting aspects of its environment with active behaviour rather than in a more inactive way. Stereotypy levels are also likely to be influenced by the general propensity of the individual to develop inflexible behavioural routines. Furthermore, as a stereotypy develops and becomes more habit-like it may be performed in circumstances where well-being is not at stake. Thus when comparing animals, lower levels of stereotypy do not necessarily reflect better well-being. General rules about the levels of stereotypy that are deemed “acceptable” from a welfare point of view are of limited use in reducing animal suffering unless they take take these factors into account. There is a great need for more research into the developmental processes responsible for stereotypies.
Article
This paper describes the demise of rinderpest, focussing on the 20th Century and especially the period of the Global Rinderpest Eradication Programme, before proceeding to describe the process of accreditation of rinderpest freedom which is now virtually complete.
Article
Bluetongue is an arthropod-transmitted viral disease of ruminants and certain other animals that was recognized and described more than 100 years ago in southern Africa. Bluetongue virus (BTV) infection of ruminants and vector Culicoides insects is enzootic throughout tropical and temperate regions of the world; however, there have been drastic recent regional alterations in the global distribution of BTV infection, particularly in Europe since 1998. Multiple novel BTV serotypes also have been detected since 1998 in the south-eastern United States, apparently encroaching from the adjacent Caribbean ecosystem, and novel serotypes of BTV have been identified recently in other historically enzootic regions of the world, including the Middle East and Australia. It has been proposed, but certainly not proven, that global climate change is responsible for these events. BTV infection of ruminants is often subclinical, but outbreaks of severe disease occur with regular frequency especially at the upper and lower limits of the virus' global range where infection is highly seasonal - occurring in the late summer and autumn. Bluetongue disease results from vascular injury, likely through a process analogous to that of human hemorrhagic viral fevers in which production of vasoactive mediators from virus-infected macrophages and dendritic cells results in enhanced endothelial paracellular permeability with subsequent vascular leakage and hypovolemic shock.
Article
The role of various environmental factors in the pathogenesis of immune mediated diseases is well established. Of which, factors entailing an immune adjuvant activity such as infectious agents, silicone, aluminium salts and others were associated with defined and non-defined immune mediated diseases both in animal models and in humans. In recent years, four conditions: siliconosis, the Gulf war syndrome (GWS), the macrophagic myofasciitis syndrome (MMF) and post-vaccination phenomena were linked with previous exposure to an adjuvant. Furthermore, these four diseases share a similar complex of signs and symptoms which further support a common denominator.Thus, we review herein the current data regarding the role of adjuvants in the pathogenesis of immune mediated diseases as well as the amassed data regarding each of these four conditions. Relating to the current knowledge we would like to suggest to include these comparable conditions under a common syndrome entitled ASIA, "Autoimmune (Auto-inflammatory) Syndrome Induced by Adjuvants".
Article
The long-term efficacy of three commercially available inactivated vaccines against bluetongue virus serotype 8 (BTV-8) (BLUEVAC) 8, Zulvac 8, and BTVPUR AlSap 8) was evaluated in a seroprevalence study and challenge experiments. Seroprevalences 1 year after vaccination ranged from 75% to 100%. In two infection experiments, groups of vaccinated sheep and cattle selected either randomly or for low antibody levels were challenged with a European BTV-8 strain 12 months after vaccination. With two exceptions, all animals, including those with low antibody levels prior to challenge, were protected from viral replication and clinical disease even at low initial antibody levels. Vaccination of susceptible ruminants in yearly intervals is thus considered an adequate scheme for BTV-8 control in Europe.
Article
Unlabelled: With the wide application of nanoscaled particles, the risk of human exposure to these particles has been markedly increased. However, knowledge about their safety falls far behind the utility of these nanoparticles. Here we have analyzed the activation of brain microglia and astrocytes, which are sensitive to changes of brain environment after peripheral exposure to nanoscaled aluminum oxide suspension. Sprague-Dawley rats (six rats per treatment) were intraperitoneally injected once every second day for 30 or 60 days with nanoscaled aluminum oxide (NSAO; 1 mg/kg or 50 mg/kg), non-nanoscaled aluminum oxide (nNSAO, 1 mg/kg), or vehicle (saline). After 60 days' exposure the numbers of ED1+, GFAP+, and nestin+ cells in cortex and hippocampus were significantly higher in NSAO-treated rats than nNSAO- or vehicle-treated rats; thus, compared with nNSAO, NSAO has potential effects on the innate immune system of rat brain. This should be considered when evaluating the toxicological effects of nanosized particles. From the clinical editor: Sprague-Dawley rats were intraperitoneally injected with nanosized aluminum oxide, (NSAO); non-nanoscaled aluminum oxide, or vehicle (saline). The numbers of ED1+, GFAP+, and nestin+ cells in cortex and hippocampus were significantly higher in NSAO-treated rats than nNSAO- or vehicle-treated rats; thus, NSAO has potential effects on the innate immune system of rat brain.
Article
Bluetongue has been recognized as a viral disease of livestock for more than 100 years. Repeated incursions of Bluetongue into Europe since 1998 have been particularly devastating for highly sensitive European fine-wool sheep breeds, and have resulted in a resurgence of interest in vaccine manufacture. Fortunately, the virus and its serology are well understood and vaccination prevents the disease. However, current vaccines are not without their problems, and many new approaches are being tested to improve the safety and breadth of protection afforded. This review describes the leading technologies for improved bluetongue vaccines and looks ahead to how advances in other viral vaccines might be applied to this disease.
Article
This report highlights the role of vaccination in the present and future food animal industry in the framework of the disease policy of the European Commission. Vaccination was essential in the virtual eradication of foot-and-mouth disease and classical swine fever, the use of modern marker vaccines opens prospects for eradication of viruses in countries with a high prevalence, and a rebirth of interest in bacterial vaccines is noted, because of the problems of drug resistance and antimicrobial residues. Biotechnology has already led to the development of several new vaccines, and to the improvement of current vaccines, and it still holds great potential for designing basically novel vaccines. Vaccination, thus, is a crucial tool in reducing the enormous economic losses caused by diseases in food animals.
Article
The objective was to determine the effects of reducing the plasma cortisol rise in calves following castration on plasma ACTH concentrations, keyhole limpet hemocyanin (KLH)- and concanavalin A (Con A)-induced in vitro interferon (IFN)-gamma production, white blood cell (WBC) numbers, neutrophil:lymphocyte (N:L) ratio, plasma haptoglobin and fibrinogen concentrations, ADG, and ADFI. Forty 5-mo-old Friesian bull calves (169 +/- 1.7 kg) were assigned to four treatments: 1) control (CON); 2) oral metyrapone administration (MET); 3) surgical castration at 0 h on d 0 (SURG); and 4) oral metyrapone administration and surgical castration (MET+SURG). Cortisol, ACTH, IFN-gamma production, haptoglobin, fibrinogen, ADFI, and ADG were not different between CON and MET animals. The MET+SURG calves had lower (P < .001) peak and mean cortisol during .25 to 1.5 h than SURG animals, but area under the cortisol vs time curve from 0 to 12 h did not differ (P > .39) between SURG and MET+SURG calves. Peak ACTH concentrations and area under the ACTH vs time curve from 0 to 6 h were greater (P < .05) for MET+SURG than for SURG calves. There were no differences between MET+SURG and SURG animals in IFN-gamma production, WBC numbers, and ADFI. On d 1, MET+SURG and SURG animals had lower (P < .01) KLH- and Con A-induced IFN-gamma production and higher (P < .05) neutrophil numbers and N:L ratio compared with CON animals. Plasma haptoglobin on d 1 and 3 and fibrinogen concentrations on d 3 and 7 were elevated (P < .05) for MET+SURG and SURG compared with CON animals, whereas SURG animals had greater (P < .05) haptoglobin and fibrinogen concentrations than MET+SURG animals on d 7. The ADG of SURG calves was lower (P < .05) than that of MET+SURG calves during d 0 to 7. Metyrapone treatment partially suppressed cortisol and increased ACTH in castrated calves but did not alter the castration-induced suppression of IFN-gamma and increases in neutrophil numbers and the N:L ratio.
Article
The use of behavioural tests aiming to assess the psychological components of stress in animals has led to divergent and sometimes arbitrary interpretations of animal behaviour. This paper presents a critical evaluation of behavioural methods currently used to investigate stress and emotionality. One of its main goals is to demonstrate, through experimental evidence, that emotionality may no longer be seen as a unidimensional construct. Accordingly, following a discussion about concepts, we propose a multiple-testing approach, paralleled by factor analyses, as a tool to dissociate and study the different dimensions of emotionality. Within this multidimensional context, genetic studies (illustrated here by different rat models) are shown to be particularly useful to investigate the neurobiology of stress/emotionality. A genetic approach can be used (i) to broaden and dissect the variability of responses within and between populations and (ii) to search for the molecular bases (i.e. genes and gene products) which underlie such a variability.
Article
This study examined characteristics of visual recognition of familiar and unfamiliar faces in sheep using a 2-way discrimination task. Of particular interest were effects of lateralisation and the differential use of internal (configurational) vs external features of the stimuli. Animals were trained in a Y-maze to identify target faces from pairs, both of which were familiar (same flock as the subjects) or both of which were unfamiliar (different flock). Having been trained to identify the rewarded face a series of stimuli were presented to the sheep, designed to test for the use of each visual hemifield in the discriminations and the use of internal and external facial cues. The first experiment showed that there was a left visual hemifield (LVF) advantage in the identification of 'hemifaces', and 'mirrored hemifaces' and 'chimeric' faces and that this effect was strongest with familiar faces. This represents the first evidence for visual field bias outside the primate literature. Results from the second experiment showed that, whilst both familiar and unfamiliar faces could be identified by the external features alone, only the familiar faces could be recognised by the internal features alone. Overall the results suggest separate recognition methods for socially familiar and unfamiliar faces, with the former being coded more by internal, configurational cues and showing a lateral bias to the left visual field.