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Pig-to-non human primate

Steven F Merkel, Allison M Andrews, Evan M Lutton, Dakai Mu, Eloise Hudry, Bradley T Hyman, Casey A Maguire, Servio H Ramirez
Developing therapies for central nervous system (CNS) diseases is exceedingly difficult due to the blood-brain barrier (BBB). Notably, emerging technologies may provide promising new options for the treatment of CNS disorders. Adeno-associated virus serotype 9 (AAV9) has been shown to transduce cells in the CNS following intravascular administration in rodents, cats, pigs, and non-human primates. These results suggest that AAV9 is capable of crossing the BBB. However, mechanisms that govern AAV9 transendothelial trafficking at the BBB remain unknown...
October 8, 2016: Journal of Neurochemistry
Gokul Swaminathan, Elizabeth A Thoryk, Kara S Cox, Jeffrey S Smith, Jayanthi J Wolf, Marian E Gindy, Danilo R Casimiro, Andrew J Bett
Dengue virus has emerged as an important arboviral infection worldwide. As a complex pathogen, with four distinct serotypes, the development of a successful Dengue virus vaccine has proven to be challenging. Here, we describe a novel Dengue vaccine candidate that contains truncated, recombinant, Dengue virus envelope protein from all four Dengue virus serotypes (DEN-80E) formulated with ionizable cationic lipid nanoparticles (LNPs). Immunization studies in mice, Guinea pigs, and in Rhesus macaques, revealed that LNPs induced high titers of Dengue virus neutralizing antibodies, with or without co-administration or encapsulation of a Toll-Like Receptor 9 agonist...
October 5, 2016: Scientific Reports
Rachel Tanner, Helen McShane
Tuberculosis (TB) remains a serious global health threat and an improved vaccine is urgently needed. New candidate TB vaccines are tested using preclinical animal models such as mice, guinea pigs, cattle and non-human primates. Animals are routinely infected with virulent Mycobacterium tuberculosis (M.tb) in challenge experiments to evaluate protective efficacy, raising ethical issues regarding the procedure of infection itself, symptoms of disease and humane end-points. We summarise the importance and limitations of animal models in TB vaccine research and review current alternatives and modifications in the context of the NC3Rs framework for replacing, reducing and refining the use of animals for scientific purposes...
September 26, 2016: ALTEX
Bjoern Petersen, Antje Frenzel, Andrea Lucas-Hahn, Doris Herrmann, Petra Hassel, Sabine Klein, Maren Ziegler, Klaus-Gerd Hadeler, Heiner Niemann
BACKGROUND: Xenotransplantation is considered to be a promising solution to the growing demand for suitable donor organs for transplantation. Despite tremendous progress in the generation of pigs with multiple genetic modifications thought to be necessary to overcoming the severe rejection responses after pig-to-non-human primate xenotransplantation, the production of knockout pigs by somatic cell nuclear transfer (SCNT) is still an inefficient process. Producing genetically modified pigs by intracytoplasmic microinjection of porcine zygotes is an alluring alternative...
September 2016: Xenotransplantation
Iris Bosschem, Bram Flahou, Jaco Bakker, Edwin Heuvelman, Jan A M Langermans, Ellen De Bruyne, Myrthe Joosten, Annemieke Smet, Richard Ducatelle, Freddy Haesebrouck
BACKGROUND: Helicobacter suis (H. suis) is the most prevalent gastric non-H. pylori Helicobacter species in humans. This bacterium mainly colonizes the stomach of pigs, but it has also been detected in the stomach of nonhuman primates. The aim of this study was to obtain better insights into potential differences between pig- and primate-associated H. suis strains in virulence and pathogenesis. MATERIALS AND METHODS: In vitro-isolated H. suis strains obtained from pigs, cynomolgus monkeys (Macaca fascicularis), and rhesus monkeys (Macaca mulatta) were used for intragastric inoculation of BALB/c mice and Mongolian gerbils...
August 24, 2016: Helicobacter
Jasper Fuk-Woo Chan, Cyril Chik-Yan Yip, Jessica Oi-Ling Tsang, Kah-Meng Tee, Jian-Piao Cai, Kenn Ka-Heng Chik, Zheng Zhu, Chris Chung-Sing Chan, Garnet Kwan-Yue Choi, Siddharth Sridhar, Anna Jinxia Zhang, Gang Lu, Kin Chiu, Amy Cheuk-Yin Lo, Sai-Wah Tsao, Kin-Hang Kok, Dong-Yan Jin, Kwok-Hung Chan, Kwok-Yung Yuen
Zika virus (ZIKV) is unique among human-pathogenic flaviviruses by its association with congenital anomalies and trans-placental and sexual human-to-human transmission. Although the pathogenesis of ZIKV-associated neurological complications has been reported in recent studies, key questions on the pathogenesis of the other clinical manifestations, non-vector-borne transmission and potential animal reservoirs of ZIKV remain unanswered. We systematically characterized the differential cell line susceptibility of 18 human and 15 nonhuman cell lines to two ZIKV isolates (human and primate) and dengue virus type 2 (DENV-2)...
August 24, 2016: Emerging Microbes & Infections
Elena Plotzki, Martina Keller, Daniel Ivanusic, Joachim Denner
Porcine cytomegalovirus (PCMV) may be harmful for human recipients if xenotransplantation using pig cell, tissue or organ will be performed transmitting the virus from donor pigs to human recipients. PCMV is widespread in pigs and closely related to human pathogenic herpesviruses, however there are no data concerning infection of humans. In contrast, recently it had been shown that transplantation of organs from pigs infected with PCMV into non-human primate recipients resulted in a significant reduction of the survival time compared with the transplantation of organs from uninfected pigs...
October 2016: Journal of Immunological Methods
Christopher P Regan, Pierre Morissette, Hillary K Regan, Jeffery J Travis, Pamela Gerenser, Jianzhong Wen, Kevin Fitzgerald, Shaun Gruver, Joseph J DeGeorge, Frederick J Sannajust
: In 2015, European and U.S. health agencies issued warning letters in response to 9 reported clinical cases of severe bradycardia/bradyarrhythmia in hepatitis C virus (HCV)-infected patients treated with sofosbuvir (SOF) in combination with other direct acting antivirals (DAAs) and the antiarrhythmic drug, amiodarone (AMIO). We utilized preclinical in vivo models to better understand this cardiac effect, the potential pharmacological mechanism(s), and to identify a clinically translatable model to assess the drug-drug interaction (DDI) cardiac risk of current and future HCV inhibitors...
July 30, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Hyun-Je Kim, Il-Hee Yoon, Byoung-Hoon Min, Yong-Hee Kim, Jun-Seop Shin, Jong-Min Kim, Jung-Sik Kim, Hye-Young Nam, Won-Woo Lee, Chung-Gyu Park
BACKGROUND: Recent progress in xenotransplantation of porcine islets to non-human primates (NHPs) gives hope for human clinical trials in the near future. Thus, implementation of an appropriate monitoring method to detect the development of detrimental porcine antigen-specific cellular immune responses is necessary. The enzyme-linked immunospot (ELISpot) assay has been widely used to monitor antigen-specific alloreactive T-cell responses in humans; however, the utility of porcine islet-specific ELISpot assay has not yet been thoroughly evaluated for pig-to-NHPs intraportal islet xenotransplantation...
July 2016: Xenotransplantation
Jun-Seop Shin, Byoung-Hoon Min, Jong-Min Kim, Jung-Sik Kim, Il Hee Yoon, Hyun Je Kim, Yong-Hee Kim, Jae Yool Jang, Hee Jung Kang, Dong-Gyun Lim, Jongwon Ha, Sang-Joon Kim, Chung-Gyu Park
BACKGROUND: Islet allotransplantation is a promising way to treat some type 1 diabetic (T1D) patients with frequent hypoglycemic unawareness, and islet xenotransplantation is emerging to overcome the problem of donor organ shortage. Our recent study showing reproducible long-term survival of porcine islets in non-human primates (NHPs) allows us to examine whether autologous regulatory T-cell (Treg) infusion at peri-transplantation period would induce transplantation tolerance in xenotransplantation setting...
July 2016: Xenotransplantation
Henna Myllymäki, Carina A Bäuerlein, Mika Rämet
Tuberculosis (TB) is a global health emergency. Up to one-third of the world's population is infected with Mycobacterium tuberculosis, and the pathogen continues to kill 1.5 million people annually. Currently, the means for preventing, diagnosing, and treating TB are unsatisfactory. One of the main reasons for the poor progress in TB research has been a lack of good animal models to study the latency, dormancy, and reactivation of the disease. Although sophisticated in vitro and in silico methods suitable for TB research are constantly being developed, they cannot reproduce the complete vertebrate immune system and its interplay with pathogens and vaccines...
2016: Frontiers in Immunology
Logan Banadyga, Michael A Dolan, Hideki Ebihara
Ebola, Marburg, and Ravn viruses, all filoviruses, are the causative agents of severe hemorrhagic fever. Much of what we understand about the pathogenesis of filovirus disease is derived from work with animal models, including nonhuman primates, which are considered the "gold standard" filovirus model since they faithfully recapitulate the clinical hallmarks of filovirus disease. However, rodent models, including the mouse, guinea pig, and hamster, also exist for Ebola, Marburg, and Ravn viruses, and although they may not reproduce all the clinical signs of filovirus disease, thanks to their relative ease of use and low cost, they are often the first choice for initial descriptions of virus pathogenesis and evaluation of antiviral prophylactics and therapeutics...
August 28, 2016: Journal of Molecular Biology
Maria Teresa Armua-Fernandez, Deborah Joekel, Alexander Schweiger, Ramon Marc Eichenberger, Jun Matsumoto, Peter Deplazes
Susceptibility/resistance to larval Echinococcus multilocularis infection varies greatly depending on host species and strains. Whereas several mice strains and non-human primates are highly susceptible to alveolar echinococcosis, rats and most of humans are considered as more resistant. In this study, we aimed to elucidate factors responsible for host resistance in rats (Experiments A-D). (A) The parasite establishment was not observed in immunocompetent Wistar rats orally inoculated with sodium hypochlorite resistant eggs with/without pig bile, or activated/non-activated oncospheres (NAO)...
September 2016: Parasitology
Simone Renner, Britta Dobenecker, Andreas Blutke, Susanne Zöls, Rüdiger Wanke, Mathias Ritzmann, Eckhard Wolf
The prevalence of diabetes mellitus, which currently affects 387 million people worldwide, is permanently rising in both adults and adolescents. Despite numerous treatment options, diabetes mellitus is a progressive disease with severe comorbidities, such as nephropathy, neuropathy, and retinopathy, as well as cardiovascular disease. Therefore, animal models predictive of the efficacy and safety of novel compounds in humans are of great value to address the unmet need for improved therapeutics. Although rodent models provide important mechanistic insights, their predictive value for therapeutic outcomes in humans is limited...
July 1, 2016: Theriogenology
M Wackermannová, L Pinc, L Jebavý
Olfaction enables most mammalian species to detect and discriminate vast numbers of chemical structures called odorants and pheromones. The perception of such chemical compounds is mediated via two major olfactory systems, the main olfactory system and the vomeronasal system, as well as minor systems, such as the septal organ and the Grueneberg ganglion. Distinct differences exist not only among species but also among individuals in terms of their olfactory sensitivity; however, little is known about the mechanisms that determine these differences...
July 18, 2016: Physiological Research
Ming-Xu Zhang, Hong-Yi Zheng, Jin Jiang, Wei Pang, Gao-Hong Zhang, Yong-Tang Zheng
Non-human primates are natural virus reservoirs, whether wild or domestic. In this study, we determined the seroprevalence of common viruses by ELISA in a northern pig-tailed macaque (Macaca leonina) colony derived from Ho Chi Minh City, Vietnam. A total of 20 types of virus which are commonly selected as target microorganisms for specific-pathogen-free colonies, or which have zoonotic potential were included in this study. The results showed only 2 in 90 northern pig-tailed macaques were seronegative for all the detected viruses, and at least 16 out of the total 20 types of virus tested were prevalent in this colony, so these macaques were commonly infected by various viruses...
July 2016: Primates; Journal of Primatology
Vladimir A Morozov, Alexey V Morozov, Joachim Denner
Pigs are frequently infected with porcine cytomegalovirus (PCMV). Infected adult animals may not present with symptoms of disease, and the virus remains latent. However, the virus may be transmitted to human recipients receiving pig transplants. Recently, it was shown that pig-to-non-human-primate xenotransplantations showed 2 to 3 times lower transplant survival when the donor pig was infected with PCMV. Therefore, highly sensitive methods are required to select virus-free pigs and to examine xenotransplants...
May 2016: Archives of Virology
Heiner Niemann, Bjoern Petersen
The domestic pig shares many genetic, anatomical and physiological similarities to humans and is thus considered to be a suitable organ donor for xenotransplantation. However, prior to clinical application of porcine xenografts, three major hurdles have to be overcome: (1) various immunological rejection responses, (2) physiological incompatibilities between the porcine organ and the human recipient and (3) the risk of transmitting zoonotic pathogens from pig to humans. With the introduction of genetically engineered pigs expressing high levels of human complement regulatory proteins or lacking expression of α-Gal epitopes, the HAR can be consistently overcome...
June 2016: Transgenic Research
David K C Cooper, Mohamed B Ezzelarab, Hidetaka Hara, Hayato Iwase, Whayoung Lee, Martin Wijkstrom, Rita Bottino
The immunologic barriers to successful xenotransplantation are related to the presence of natural anti-pig antibodies in humans and non-human primates that bind to antigens expressed on the transplanted pig organ (the most important of which is galactose-α1,3-galactose [Gal]), and activate the complement cascade, which results in rapid destruction of the graft, a process known as hyperacute rejection. High levels of elicited anti-pig IgG may develop if the adaptive immune response is not prevented by adequate immunosuppressive therapy, resulting in activation and injury of the vascular endothelium...
March 2016: Xenotransplantation
S J Padayatty, M Levine
Vitamin C (Ascorbic Acid), the antiscorbutic vitamin, cannot be synthesized by humans and other primates, and has to be obtained from diet. Ascorbic acid is an electron donor and acts as a cofactor for fifteen mammalian enzymes. Two sodium-dependent transporters are specific for ascorbic acid, and its oxidation product dehydroascorbic acid is transported by glucose transporters. Ascorbic acid is differentially accumulated by most tissues and body fluids. Plasma and tissue vitamin C concentrations are dependent on amount consumed, bioavailability, renal excretion, and utilization...
September 2016: Oral Diseases
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