This article is from Viruses , volume 2 . Abstract Adenovirus vectors have significant potential for long- or short-term gene transfer. Preclinical and clinical studies using human derived adenoviruses (HAd) have demonstrated the feasibility of flexible hybrid vector designs, robust expression and induction of protective immunity. However, clinical use of HAd vectors can, under some conditions, be limited by pre-existing vector immunity. Pre-existing humoral and cellular anti-capsid immunity limits the efficacy and duration of transgene expression and is poorly circumvented by injections of larger doses and immuno-suppressing drugs. This review updates canine adenovirus serotype 2 (CAV-2, also known as CAdV-2) biology and gives an overview of the generation of early region 1 (E1)-deleted to helper-dependent (HD) CAV-2 vectors. We also summarize the essential characteristics concerning their interaction with the anti-HAd memory immune responses in humans, the preferential transduction of neurons, and its high level of retrograde axonal transport in the central and peripheral nervous system. CAV-2 vectors are particularly interesting tools to study the pathophysiology and potential treatment of neurodegenerative diseases, as anti-tumoral and anti-viral vaccines, tracer of synaptic junctions, oncolytic virus and as a platform to generate chimeric vectors.
Published on 10/24/2014
Document details: 18 downloads.
This article is from The Journal of Veterinary Medical Science , volume 76 . Abstract Regulatory T cells (Tregs) suppress the immune system and maintain the homeostasis of the immune system in healthy dogs. In septic patients, the percentage of circulating Tregs is increasing, which may cause the sepsis-induced immunosuppression. This study was performed to investigate the changes of the percentage of Tregs in total lymphocytes of the peripheral blood in the experimental canine endotoxemia model. The animals injected with a high dose lipopolysaccharide (LPS) induced severe leukopenia followed by leukocytosis, but the total lymphocytes number was relatively consistent. As a result of flow cytometric analysis, the percentage of Tregs in total lymphocytes of the peripheral blood was 8.45 ± 1.30% (day 0), and it temporarily decreased 2.54 ± 1.16% (day 1) and increased continuously until the end of the experiment (14.34 ± 4.10% on day 3 and 25.70 ± 7.39% on day 7), respectively. This study provides basic information in physiologic and immunologic changes in Tregs in dogs with sepsis model.
Published on 10/19/2014
Document details: 54 downloads.
This article is from Veterinary Research , volume 43 . Abstract Mycoplasma haemocanis is a hemotrophic mycoplasma (hemoplasma), blood pathogen that may cause acute disease in immunosuppressed or splenectomized dogs. The genome of the strain Illinois, isolated from blood of a naturally infected dog, has been entirely sequenced and annotated to gain a better understanding of the biology of M. haemocanis. Its single circular chromosome has 919 992 bp and a low G + C content (35%), representing a typical mycoplasmal genome. A gene-by-gene comparison against its feline counterpart, M. haemofelis, reveals a very similar composition and architecture with most of the genes having conserved synteny extending over their entire chromosomes and differing only by a small set of unique protein coding sequences. As in M. haemofelis, M. haemocanis metabolic pathways are reduced and apparently rely heavily on the nutrients afforded by its host environment. The presence of a major percentage of its genome dedicated to paralogous genes (63.7%) suggests that this bacterium might use antigenic variation as a mechanism to evade the host’s immune system as also observed in M. haemofelis genome. Phylogenomic comparisons based on average nucleotide identity (ANI) and tetranucleotide signature suggest that these two pathogens are different species of mycoplasmas, with M. haemocanis infecting dogs and M. haemofelis infecting cats.
Published on 10/28/2014
Document details: 50 downloads.
Canine Parvovirus VP2 Protein Expressed in Silkworm Pupae Self-Assembles into Virus-Like Particles with High Immunogenicity.
This article is from PLoS ONE , volume 9 . Abstract The VP2 structural protein of parvovirus can produce virus-like particles (VLPs) by a self-assembly process in vitro, making VLPs attractive vaccine candidates. In this study, the VP2 protein of canine parvovirus (CPV) was expressed using a baculovirus expression system and assembled into parvovirus-like particles in insect cells and pupae. Electron micrographs of VLPs showed that they were very similar in size and morphology when compared to the wild-type parvovirus. The immunogenicity of the VLPs was investigated in mice and dogs. Mice immunized intramuscularly with purified VLPs, in the absence of an adjuvant, elicited CD4+ and CD8+ T cell responses and were able to elicit a neutralizing antibody response against CPV, while the oral administration of raw homogenates containing VLPs to the dogs resulted in a systemic immune response and long-lasting immunity. These results demonstrate that the CPV-VLPs stimulate both cellular and humoral immune responses, and so CPV-VLPs may be a promising candidate vaccine for the prevention of CPV-associated disease.
Published on 10/28/2014
Document details: 45 downloads.
The protective immune response produced in dogs after primary vaccination with the LiESP/QA-21 vaccine (CaniLeish®) remains effective against an experimental challenge one year later.
This article is from Veterinary Research , volume 45 . Abstract Control of canine leishmaniasis is an important objective for the benefit of dogs living in or visiting endemic areas and for public health because of the zoonotic nature of this disease. Resistance or susceptibility to developing canine leishmaniasis after exposure to Leishmania infantum is primarily determined by the ability of the immune system to develop an appropriate Th1-dominated specific response to the parasite. For this reason there is a need for effective canine vaccines that can decrease the number of dogs developing progressive infections. In this study, we followed the impact of the LiESP/QA-21 canine vaccine (composed of excreted-secreted proteins of L. infantum and the QA-21 saponin adjuvant), recently launched commercially in Europe, on selected humoral and cellular immune parameters following an infectious intravenous challenge with L. infantum promastigotes administered one year after the primary vaccine course. We also followed parasitological parameters to determine the parasitological status of the challenged dogs. In contrast to controls, vaccinated dogs retained significantly stronger cell-mediated immune responses against the parasite despite a virulent challenge and had significantly lower mean parasite burdens at the end of the study, associated with a lower probability of developing active infections. These results confirm that the immune responses generated by vaccination with LiESP/QA-21 are still effective against an intravenous challenge one year after the primary vaccine course.
Published on 10/17/2014
Document details: 40 downloads.
Three-dimensional mapping of differential amino acids of human, murine, canine and equine TLR4/MD-2 receptor complexes conferring endotoxic activation by lipid A, antagonism by Eritoran and species-dependent activities of Lipid IVA in the mammalian LPS sensor system.
This article is from Computational and Structural Biotechnology Journal , volume 7 . Abstract A literature review concerning the unexpected species differences of the vertebrate innate immune response to lipid IVA was published in CSBJ prior to the present computational study to address the unpaired activity-sequence correlation of prototypic E. coli -type lipid A and its precursor lipid IVA regarding human, murine, equine and canine species. To this end, their sequences and structures of hitherto known Toll-like receptor 4 (TLR4) and myeloid differentiation factor 2 (MD-2) complexes were aligned and their differential side chain patterns studied. If required due to the lack of the corresponding X-ray crystallographic data, three-dimensional models of TLR4/MD-2/ligand complexes were generated using mono and dimeric crystal structures as templates and in silico docking of the prototypic ligands lipid A, lipid IVA and Eritoran. All differential amino acids were mapped to pinpoint species dependency on an atomic scale, i.e. the possible concert of mechanistically relevant side chains. In its most abstract and general form the three-dimensional (3D-) models devise a triangular interface or “wedge” where molecular interactions between TLR4, MD-2 and ligand itself take place. This study identifies two areas in the wedge related to either agonism or antagonism reflecting why ligands like lipid IVA can possess a species dependent dual activity. Lipid IVA represents an imperfect (underacylated and backbone-flipped), low affinity ligand of mammalian TLR4/MD-2 complexes. Its specific but weak antagonistic activity in the human system is in particular due to the loss of phosphate attraction in the wedge-shaped region conferred by nonhomologous residue changes when compared to crystal and modeled structures of the corresponding murine and equine TLR4/MD-2 complexes. The counter-TLR4/MD-2 unit was also taken into account since agonist-mediated dimerization in a defined m-shaped complex composed of two TLR4/MD-2/agonist subunits triggers intracellular signaling during the innate immune response to bacterial endotoxin exposure.
Published on 10/23/2014
Document details: 35 downloads.
The everything dog health book : a complete guide to keeping your best friend healthy from head to tail
Published on 06/26/2009
Document details: 328 pages. 45 downloads.
DTIC ADA501663: Adoptive Immunotherapy Combined with Hematopoietic Cell Transplantation as a Therapeutic Approach to Treatment of Prostate Cancer
We determined that cell lysates prepared from canine prostate tissue was immunogenic when injected in female dogs. In addition to the known prostate antigen, canine prostate specific esterase (CPSE), we identified by molecular weight several other proteins against which the dog made IgG antibodies. Using a mixed lymphocyte reaction, we found that a cellular response was generated against the prostate cell lysate after the female dog was injected 3 times with antigen. Sensitization of female dogs with prostate antigen suspended in incomplete Freund's adjuvant appeared to be superior to prostate lysate antigen-loaded canine autologous dendritic cells when both were injected subcutaneously near the popliteal lymph node. Peripheral blood lymphocytes and lymph node-derived lymphocytes reacted to prostate lysate in the mixed lymphocyte reaction. An immune response to prostate lysate or CPSE was not adequately detected by a delayed-type hypersensitivity reaction 10 days after the last of three subcutaneous injections of antigen. Two of three male dogs transplanted with dog leukocyte identical female bone marrow engrafted, but additional time is need to ensure engraftment is stable before prostate antigen sensitized donor lymphocytes can be infused into the recipient for an anti-prostate immune response to be evaluated.
Published on 07/22/2018
Document details: 14 pages. 3 downloads.
A model system for determining skin histocompati bility in man has been described, based upon the acceleration of grafts on an indifferent recipient immunized previously by one member of the donor-recipient pair to be tested. An alpha-1 glyco-protein isolated from the serum and concentrated in thymic tissue prolonged the life of 30% of homologous skin grafts in rats for 6 months. Utilizing immunosuppressive therapy in the form of Umuran, Actinomycin-C, Azaserinecortisone, prolonged tolerance for a human renal homograft from a nontwin donor in 5 recipients was produced. In one of these a kideny transplanted from a cadaver has functioned well enough to sustain active life for 15 months. An inlying plastic conduit for the performance of long-term, chronic peritoneal irrigation is described and has been utilized by two patients performing peritoneal dialysis at home for a period of 9 months. Homograft antigens on canine platelets have been isolated in soluble form. Homograft antibody elicited from rejected canine kidneys in a soluble fluid phase will react with this antigen in the classic immune reaction of agglutination complement fixation and immune adherence.
Published on 05/11/2018
Document details: 8 pages. 10 downloads.
DTIC ADA510024: Adoptive Immunotherapy Combined with Hematopoietic Cell Transplantation as a Therapeutic Treatment of Prostate Cancer
We determined that a prostate cell lysate prepared from canine prostate tissue was immunogenic when injected in female dogs. In addition to the known prostate antigen, canine prostate specific esterase (CPSE), we identified by molecular weight several other proteins against which the dog made IgG antibodies. Using a mixed lymphocyte reaction, we found that a cellular response was generated against the prostate cell lysate after the female dog was injected 3 times with antigen. Sensitization of female dogs with prostate antigen suspended in incomplete Freund's adjuvant appeared to be superior to prostate lysate antigen loaded canine autologous dendritic cells when both were injected subcutaneously near the popliteal lymph node. Peripheral blood lymphocytes and lymph node derived lymphocytes reacted to prostate lysate in the mixed lymphocyte reaction. An immune response to prostate lysate not significantly detected by a delayed-type hypersensitivity reaction 24 to 48 hours after the last of three subcutaneous injections of antigen. One of four male dogs transplanted with dog leukocyte identical female bone marrow engrafted was stably engrafted. Injection of prostate antigen-sensitized female peripheral blood mononuclear cells failed to induce prostatitis, conversion of mixed to 100% hematopoietic chimerism or initiate graft versus host disease in the male recipient. Based on a single example, these results suggest that induction of an inflammatory response against normal tissue following injection of antigen sensitized lymphocytes may require additional perturbation to the recipient's targeted tissue.
Published on 07/24/2018
Document details: 19 pages. 3 downloads.