Nanotechnologies in veterinary medicine: introduction

Charley Bernard. Les nanotechnologies en médecine vétérinaire : introduction. In: Bulletin de l'Académie Vétérinaire de France tome 166 n°2, 2013. pp. 129-130

Contribution of veterinary vaccines to new knowledge in vaccinology

Vaccines are frequently used in veterinary medicine to protect numerous domestic animal species against a long list of pathogens. A noticeable part of commercialized or registered veterinary vaccines use new technologies such as recombinant proteins, deletion of virulence genes, viral vectors, DNA vaccination. These vaccines may also contain a variety of adjuvants. In addition, veterinary research on new vaccine strategies, which allows direct evaluation of protection in target animal species, is very active, including new vectors, nanotechnology, evaluation of TLR (Toll like receptor) ligands or cytokines as adjuvants, per cutaneous route of administration. These information contribute to new knowledge in vaccinology, including for human vaccines.La vaccination est une pratique fréquente en médecine vétérinaire pour protéger de nombreuses espèces d'animaux domestiques contre une longue liste d’agents pathogènes. Une proportion importante des vaccins vétérinaires commercialisés ou enregistrés utilisent des technologies les plus récentes : protéines recombinantes, souches délétées de gènes de virulence, vecteurs vaccinaux viraux, vaccination ADN. Ils peuvent aussi contenir des adjuvants d'origine variée : émulsions, polymères, extraits végétaux, vitamines. La recherche vétérinaire sur les vaccins, offre l'avantage de permettre d'évaluer leur effet protecteur directement sur l'espèce animale cible. Elle couvre de nombreux domaines d'innovation, dont les nouveaux vecteurs vaccinaux, l'utilisation des nanotechnologies, l'évaluation du pouvoir adjuvant de ligands de TLR (Toll like receptor) et de cytokines, la voie trans cutanée d'administration des vaccins etc. L'ensemble de ces informations contribue au progrès des connaissances dans la science de la vaccination, la vaccinologie, y compris dans ses applications pour l'Homme

Porcine innate and adaptative immune responses to influenza and coronavirus infections

Both innate and adaptative immune responses contribute to the control of infectious diseases, including by limiting the spreading of zoonotic diseases from animal reservoirs to humans. Pigs represent an important animal reservoir for influenza virus infection of human populations and are also naturally infected by coronaviruses, an important group of viruses, which includes the recently emerged severe acute respiratory syndrome (SARS) virus. Studies on both innate and adaptative immune responses of pigs to influenza virus and coronaviruses contribute, therefore, to a better control of these infections in their natural hosts and will be briefly reviewed in this article. Pro-inflammatory cytokines, including type I interferon (IFN), tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6), were found in lung secretions of influenza virus infected pigs, and correlated with the intensity of clinical signs, whereas prior vaccination against influenza strongly reduced the production of infectious virus and cytokines in the lungs upon challenge, which was associated with clinical protection. An early type I IFN production was also found in coronavirus infected pigs, including at mucosal sites. IFN induction by coronavirus is shown to involve interaction between a viral glycoprotein and a leukocyte subset, likely equivalent to plasmacytoid dendritic cells, present in the mucosae and associated lymphoid tissues. Given the IFN mediated antiviral and immunomodulatory effects, the use of IFN or IFN inducers may prove an efficient strategy for a better control of influenza virus and coronavirus infections in pigs. Because influenza and coronaviruses target mucosal surfaces, adaptative immune responses have to be characterized at mucosal sites. Thus, nasal and pulmonary antibody responses were analyzed in influenza virus infected or vaccinated pigs showing short-lived, but potentially protective local IgA and IgG antibody (Ab) responses. Interestingly, primary influenza virus infection induced long-lived increase of lung CD8(+) T cells and local lymphoproliferative responses. Pigs infected by a respiratory coronavirus (PRCV) showed virus-specific IgG Ab-secreting cells in the bronchial lymph nodes, whereas the transmissible gastroenteritis coronavirus (TGEV) induced more IgA Ab-secreting cells in gut tissues, which illustrates the importance of the route of antigen administration for inducing local immune effector mechanisms. Porcine viral infections provide, therefore, valuable models for evaluating the immune parameters that are important for controlling transmission of important viral zoonotic infections

Mesenteric lymph node cells from neonates present a prominent IL-12 response to CpG oligodeoxynucleotide via an IL-15 feedback loop of amplification

At birth, the immune system is still in development making neonates more susceptible to infections. The recognition of microbial ligands is a key step in the initiation of immune responses. It can be mimicked to stimulate the immune system by the use of synthetic ligands recognising pattern recognition receptors. In human and mouse, it has been found that neonatal cytokine responses to toll-like receptor (TLR) ligands differ in many ways from those of adults but the relevant studies have been limited to cord blood and spleen cells. In this study, we compared the responses in neonate and adult sheep to CpG oligodeoxynucleotides (ODN), a TLR9 ligand, in both a mucosal and a systemic organ. We observed that in response to CpG-ODN more IL-12 was produced by neonatal than adult sheep cells from mesenteric lymph nodes (MLN) and spleen. This higher IL-12 response was limited to the first 20 days after birth for MLN cells but persisted for a longer period for spleen cells. The major IL-12-producing cells were identified as CD14+CD11b+. These cells were poor producers of IL-12 in response to direct stimulation with CpG-ODN and required the cooperation of other MLN cells. The difference in response to CpG-ODN between neonates and adults can be attributed to both a higher proportion of CD14+CD11b+ cells in neonate lambs and their higher capacity to produce IL-15. The IL-15 increases IL-12 production by an amplifying feedback loop involving CD40

Study of type I interferon producing cells in sheep lymph draining oro-nasal mucosae or skin tissues

Interferons (IFN) are natural antiviralmolecules produced by cells as an early response to a viral aggression. To study the early production of IFN at primary sites of viral infections (i.e. mucosal or skin tissues), we used a novel lymphatic cannulation model in sheep, providing real-time access to lymph and lymph cells draining a mucosal or skin area. Following oronasal or cutaneous injection of an IFNinducing oligonucleotide, we were able to detect IFN early on in the lymph draining the injection site, as well as IFN-producing lymph cells migrating from the injection site to the draining lymph node. These rare cells (<1%) share the same features as plasmacytoid dendritic cells (low density, Bneg CD11cneg CD45RBpos, expressing TLR7 and 9, and IRF7 transcripts). They play an important role in the activation of adaptive immunity, and could provide interesting targets for innovative vaccine strategies.Les interférons (IFN) constituent une famille de molécules naturelles antivirales dont la fabrication par les cellules est déclenchée dès les premières phases d'une agression virale. Afin d'étudier cette production précoce au plus près des sites primaires d'infection virale (muqueuses ou peau), nous avons utilisé un modèle original de cathétérisme lymphatique chez le mouton, qui permet d'accéder en temps réel à la lymphe et aux cellules lymphatiques drainant un territoire muqueux ou cutané. Après injection oro-nasale ou cutanée d'un oligonucléotide inducteur d'IFN, nous détectons la présence précoce d'IFN dans la lymphe drainant le site d'injection, ainsi que la présence de cellules lymphatiques productrices d'IFN, en migration du site d'induction vers le ganglion drainant. Ces cellules rares (<1%) ont les caractéristiques de cellules dendritiques plasmacytoïdes (faible densité, Bneg CD11cneg CD45RBpos, exprimant les transcrits des TLR 7 et 9 et de l'IRF7). Ces cellules, déterminantes dans l'activation de l'immunité adaptative, pourraient être ciblées avantageusement par des stratégies vaccinales novatrices

Antacid therapy for gastroesophageal reflux in preterm infants: a systematic review

Background: Gastro-oesophageal reflux is prevalent in preterm infants. Despite widespread use in clinical practice, there is still much controversy over the efficacy and safety of drug interventions, particularly antacid therapy. Objective: To systematically review the effects of antacid therapy on preterm infants with symptoms of gastro-oesophageal reflux, and to assess the safety of these interventions. Methods: We carried out an electronic search of the Cochrane central register of controlled trials (CENTRAL, The Cochrane Library), MEDLINE (1966–present), EMBASE (1980–present) and CINAHL (1982–present) as well as other online sources. Participants were preterm infants (<37 weeks gestation) with gastro-oesophageal reflux disease who were receiving care on a neonatal unit. We assessed the effects of histamine-2 receptor antagonists, proton pump inhibitors and alginates against placebo, primarily to see if they reduced the symptoms of reflux. Results: Six studies were included in this review. Meta-analysis could not be carried out due to a lack of studies assessing the same intervention with the same outcomes. Omeprazole therapy significantly reduced the oesophageal acid exposure percentage time with pH<4 (p<0.01) and sodium alginate significantly decreased gastro-oesophageal reflux episodes (p=0.024). Metoclopramide and ranitidine showed a significant increase in gastro-oesophageal reflux disease symptoms versus placebo (p<0.04). No significant results were found for the use of esomeprazole or lansoprazole versus placebo. Conclusions: There is insufficient evidence available to conclude whether antacid therapy is effective or safe when treating gastro-oesophageal reflux disease in preterm infants. Further research is needed into this topic and caution should be taken when administering antacids to preterm infants

Abstracts from the NIHR INVOLVE Conference 2017

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Un modèle animal d'étude in vivo d'une réponse immune innée à un coronavirus: la production d'interféron alpha en réponse au virus de la gastro-entérite transmissible (GET) du porc

Interferons are a family of molecules produced in response to a viral aggression. The author focuses here on alpha interferon, describing its biological properties (antiviral, immunomodulator, antitumoral and responsible for side effects such as fever), as well as its induction and production mechanisms. He used an experimental infection model in piglets with the transmissible gastroenteritis virus (TGEV) to describe the mechanism of alpha interferon production, the exact nature of the producing cells, which are neither T lymphocytes nor B lymphocytes, but which express the class II major histocompatibility complex. Cells with the same properties are found in man’s respiratory tract and nasal mucosa. As coronaviruses are known to trigger a very strong secretion of interferon, the author suggests the following applications : monitoring interferon blood levels as a diagnostic aid in SARS, using interferon to create a vaccine, and using its possible connection with the intensity of clinical signs, and with individual sensitivity to the virus.Les interférons constituent une famille de molécules naturelles dont la fabrication par les cellules est déclenchée par une agression virale. L’auteur traite ici de l’interféron α ; après un rappel de ses propriétés biologiques (antiviral, mais aussi immunomodulateur, antitumoral et responsable de certains effets secondaires comme la fièvre), il décrit les mécanismes d’induction et les cellules productrices. Un modèle d’infection expérimentale du porcelet par le coronavirus de la gastro-entérite transmissible (GET) ou «transmissible gastroenteritis virus» (TGEV) lui a permis de décrire la genèse de cette production chez le porcelet, la nature exacte des cellules productrices qui ne sont ni des lymphocytes T ni des lymphocytes B, mais qui expriment le complexe majeur d’histocompatibilité de classe II. Des cellules ayant les mêmes propriétés existent dans l’appareil respiratoire de l’homme et dans sa muqueuse nasale. Compte tenu du fait que les coronavirus sont connus pour induire une très forte sécrétion d’interféron, l’auteur en tire quelques conclusions sur l’intérêt de l’exploration du niveau sanguin d’interféron comme aide au diagnostic du SRAS, sur la possibilité de sa participation à l’intensité des signes cliniques, sur son emploi pour une éventuelle vaccination et sur son rôle possible dans les différences individuelles de sensibilité au virus.Charley Bernard. Un modèle animal d'étude in vivo d'une réponse immune innée à un coronavirus: la production d'interféron alpha en réponse au virus de la gastro-entérite transmissible (GET) du porc. In: Bulletin de l'Académie Vétérinaire de France tome 156 n°3, 2003. pp. 31-36

Coronavirus de la gastroenterite transmissible du porc : mecanismes d'induction, production et effets de l'interferon alpha

SIGLECNRS T Bordereau / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc