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Immuno-toxicological evaluation of her1 cancer vaccine in non-human primates: a 6-month subcutaneous study

IMMUNOPHARMACOLOGY AND IMMUNOTOXICOLOGY 2021年第3期43卷 283-290页

作者： Mancebo Rodriguez, Axel Bergado Baez, Gretchen Acosta Lago, Eric Leon Goni, Avelina Blanco Gamez, Diuris Fuentes Morales, Dasha Hernandez Fernandez, Diana Rosa Sanchez Ramirez, Belinda Perez Barreda, Aylen Casaco Parada, Angel Natl Ctr Lab Animals Breeding CENPALAB Ctr Expt Toxicol Havana Cuba Ctr Mol Immunol CIM Tumor Immunol Direct Havana Cuba Ctr Med Surg Res CIMEQ Havana Cuba

Purpose: A vaccine composition based on the extracellular domain of the human epidermal growth factor receptor 1 (HER1-ECD) and the combination of VSSP (very small size proteoliposomes) and Montanide ISA 51 adjuvants when used by intramuscular route, demonstrated promising results in preclinical studies. However, in order to avoid potential adverse events due to the use of Montanide, it is proposed to modify the vaccine formulation by using VSSP (very small size proteoliposomes) adjuvant alone, and to evaluate the quality of subcutaneously induced immune response. This study aimed to assess the immunotoxicological effects of HER1 vaccine in cercopithecus aethiops. Materials and methods: Fifteen monkeys were randomized into four groups: Negative Control (Tris/NaCl, s.c.), Positive Control (200 mu g HER1-ECD/VSSP/Montanide ISA-51 VG, i.m), Low Dose (200 mu g HER1-ECD/VSSP/Tris NaCl, s.c.) and High Dose (800 mu g HER1-ECD/VSSP/Tris NaCl, s.c). All monkeys received 7 doses and were daily inspected for clinical signs. Body weight, rectal temperature, cardiac and respiratory rates were measured during the study, and electrocardiographical and ophthalmological studies were performed. Humoral and cellular immune response and clinical pathology parameters were analyzed. Results: Animal's survival in the study was 100% (n = 15). Administration site reactions were observed in the Positive Control animals (n = 4). HER1 vaccine administered subcutaneously (High Dose Group) achieved good IgG antibody titers although lower than the Positive Control group, but with higher ability to inhibit HER1 phosphorylation. Conclusions: This suggests that the alternative of eliminating the use of Montanide in the HER1 vaccine preparation and the using subcutaneous route is feasible.

关键词： HER1 cancer vaccine repeated dose immunotoxicology cercopithecus aethiops

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Investigating The Host Range Of Neoromicia Capensis Coronavirus In Vitro

Investigating The Host Range Of Neoromicia Capensis Coronavi...

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作者： Andrea Kotze Stellenbosch University

学位级别：硕士

ENGLISH ABSTRACT: Coronaviruses are known to cause disease in humans and animals. Two important human coronaviruses that have caused epidemics are severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). These coronaviruses originated in animals and were introduced into the human population through zoonotic transmission. Neoromicia capensis coronavirus (NeoCoV), a bat coronavirus that was discovered in the South African bat species Neoromicia capensis, is 85.5% genetically identical to MERS-CoV. It is believed that NeoCoV is an ancestor of MERS-CoV; however, the potential for NeoCoV to emerge as a potential zoonotic agent has not yet been investigated. This study investigated the host range of NeoCoV in order to assess its potential to cross the species barrier from bats to other mammals. This study attempted to isolate NeoCoV in cell culture to investigate its behaviour in vitro. The host range of NeoCoV was further explored by developing viral pseudoparticles that expressed the spike proteins of NeoCoV, MERS-CoV or SARS-CoV. These pseudoparticles were used to infect various cell lines of mammalian origin to determine which animal species NeoCoV may be able to infect and if its host range has any similarities to that of MERS- and/or SARS-CoV. Attempts were made to isolate NeoCoV in cell culture by inoculating host-derived cells with NeoCoV-positive bat faecal homogenate. Attempts were proven unsuccessful by a highly sensitive quantitative reverse transcription polymerase chain reaction assay. Infecting cell lines with pseudoparticles bearing either the NeoCoV, MERS- or SARS-CoV spike protein revealed that NeoCoV could possibly utilise N. capensis kidney cells for replication, and not the lungs or trachea. Infection of Pipistrellus pipistrellus kidney cells with the three different pseudotypes yielded low levels of infection, suggesting that this cell line is less susceptible to infection by the three viru

关键词： Coronavirus infections cercopithecus aethiops Pipistrellus Kidney toxicity

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Living in a landscape of fear: the impact of predation, resource availability and habitat structure on primate range use

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ANIMAL BEHAVIOUR 2014年 88卷 165-173页

作者： Coleman, Ben T. Hill, Russell A. Univ Durham Dept Anthropol Durham DH1 3LE England Lajuma Res Ctr Primate & Predator Project Louis Trichardt Makhado South Africa

Spatial variation in predation risk generates a 'landscape of fear', with prey animals modifying their distribution and behaviour in response to this variable predation risk. In systems comprising multiple predators and prey species, a key challenge is distinguishing the independent effects of different predator guilds on prey responses. We exploited the acoustically distinct alarm calls of samango monkeys, cercopithecus mitis erythrarchus, to create a predator-specific landscape of fear from eagles to assess its impact on space use within mixed regressive-spatial regressive models incorporating data on resource distribution and structural characteristics of the environment. The landscape of fear from eagles was the most significant determinant of samango range use, with no effect of resource availability. The monkeys also selected areas of their range with higher canopies and higher understory visibility, behaviour consistent with further minimizing risk of predation. These results contrast with those of vervet monkeys, Chlorocebus aethiops pygerythrus, at the same site for which the landscapes of fear from leopards and baboons were the most significant determinants of space use. While highlighting that predation risk is a key driver of primate behaviour in this population, the landscapes of fear experienced by samango monkeys and vervet monkeys appear to differ despite exposure to identical predator guilds. This emphasizes the importance of distinguishing between the risk effects of different predators in understanding prey ecology, but also that closely related prey species may respond to these predator-specific risks in different ways. (C) 2013 The Association for the Study of Animal Behaviour. Published by Elsevier Ltd. All rights reserved.

关键词： blue monkey cercopithecus aethiops cercopithecus albogularis fruit availability geographical information system (GIS) intergroup competition local convex hulls (LoCoH) analysis spatial regression Sykes monkey

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A critical assessment of two species distribution models: a case study of the vervet monkey (cercopithecus aethiops)

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JOURNAL OF BIOGEOGRAPHY 2009年第12期36卷 2300-2312页

作者： Willems, Erik P. Hill, Russell A. Univ Durham Dept Anthropol Evolutionary Anthropol Res Grp Durham England

Aim Species distribution models are invaluable tools in biogeographical, ecological and applied biological research, but specific concerns have been raised in relation to different modelling techniques in terms of their validity. Here we compare two fundamentally different approaches to species distribution modelling, one based on simple occurrence data where the lack of an ecological framework has been criticized, and the other firmly based in socio-ecological theory but requiring highly detailed behavioural information that is often limited in availability. Location (Sub-Saharan) Africa. Methods We used two distinct techniques to predict the realized distribution of a model species, the vervet monkey (cercopithecus aethiops Linnaeus, 1758). A maximum entropy model was produced taking 13 environmental variables and presence-only data from 174 sites throughout Africa as input, with an additional 58 sites retained to test the model. A time-budget model considering the same environmental variables was constructed from detailed behavioural data on 20 groups representing 14 populations, with presence-only data from the remaining 218 sites reserved to test model predictions on vervet monkey occurrence. Both models were further validated against a reference species distribution map as drawn up by the African Mammals Databank. Results Both models performed well, with the time budget and maximum entropy algorithms correctly predicting vervet monkey presence at 78.4% and 91.4% of their respective test sites. Similarly, the time-budget model correctly predicted presence and absence at 87.4% of map pixels against the reference distribution map, and the maximum entropy model achieved a success rate of 81.8%. Finally, there was a high level of agreement (81.6%) between the presence-absence maps produced by the two models, and the environmental variables identified as most strongly driving vervet monkey distribution were the same in both models. Main conclusions The time-budget a

关键词： Africa Cercopithecidae cercopithecus aethiops maximum entropy model NDVI species distribution modelling time budget model vervet monkey

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Subcellular localization of the alphaherpesvirus serine/threonine kinase Us3 as a determinant of Us3 function

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Virulence 2010年第4期1卷 291-294页

作者： Renée L. Finnen Bruce W. Banfield Department of Microbiology and Immunology Queen’s University Kingston ON CA Department of Microbiology and Immunology Queen’s University Kingston ON CA

The Us3 serine threonine kinases perform multiple roles in alphaherpesvirus infection and can localize to distinct subcellular compartments. Transient expression of Us3 in cells results in two dramatic alterations of the actin cytoskeleton: production of actin-based filamentous processes (FPs); and breakdown of actin stress fibres giving rise to rounded cell morphology. In our recent study on FPs induced by HSV-2 Us3, we noted that FP formation was diminished when HSV-2 Us3 was trapped within the nucleus following treatment of transfected cells with leptomycin B (LMB). This observation suggested that subcellular localization of Us3 could be a determinant of Us3-induced FP formation. Here, we review what is known regarding the effect of subcellular localization of Us3 on FP production and on actin stress fibre breakdown and discuss the potential significance of studies aimed at defining the requirements for subcellular localization of Us3.

关键词： Actins/metabolism Alphaherpesvirinae/enzymology Alphaherpesvirinae/genetics Alphaherpesvirinae/physiology Animals Cell Communication Cell Nucleus/enzymology Cell Nucleus/metabolism cercopithecus aethiops Cytoskeleton/metabolism Herpesvirus 2, Human/enzymology Herpesvirus 2, Human/genetics Herpesvirus 2, Human/physiology Humans Protein-Serine-Threonine Kinases/genetics Protein-Serine-Threonine Kinases/metabolism Subcellular Fractions/enzymology Subcellular Fractions/metabolism Vero Cells Viral Proteins/genetics Viral Proteins/metabolism

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Predator-specific landscapes of fear and resource distribution: effects on spatial range use

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ECOLOGY 2009年第2期90卷 546-555页

作者： Willems, Erik P. Hill, Russell A. Univ Durham Dept Anthropol Evolutionary Anthropol Res Grp Durham DH1 3HN England

Although ecologists have long recognized that animal space use is primarily determined by the presence of predators and the distribution of resources, the effects of these two environmental conditions have never been quantified simultaneously in a single spatial model. Here, in a novel approach, predator-specific landscapes of fear are constructed on the basis of behavioral responses of a prey species (vervet monkey;cercopithecus aethiops), and we show how these can be combined with data on resource distribution to account for the observed variation in intensity of space use. Results from a mixed regressive-spatial regressive analysis demonstrate that ranging behavior can indeed be largely interpreted as an adaptive response to perceived risk of predation by some (but not all) predators and the spatial availability of resources. The theoretical framework behind the model is furthermore such that it can easily be extended to incorporate the effects of additional factors potentially shaping animal range use and thus may be of great value to the study of animal spatial ecology.

关键词： cercopithecus aethiops geographic information system (GIS) habitat selection kernel density estimation multi-predator environment perceived predation risk resource distribution spatial autocorrelation spatial regression utilization distribution

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Enzootic simian piroplasm (Entopolypoides macaci ) in wild-caught Kenyan non-human primates

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JOURNAL OF MEDICAL PRIMATOLOGY 2008年第6期37卷 329-336页

作者： Jeneby, M. M. Ngeiywa, M. Yole, D. S. Mwenda, J. M. Suleman, M. A. Carlson, H. E. Natl Museums Kenya Inst Primate Res Nairobi Kenya Moi Univ Dept Zool Eldoret Kenya Dept Neurosci Div Comparat Med Uppsala Sweden

Background Three species of non-human primates comprising African green monkeys (AGMs), (cercopithecus aethiops, n = 89), Syke's monkeys (cercopithecus mitis, n = 60) and olive baboons (Papio cynocephalus anubis, n = 30), were screened for Entopolypoides macaci. Methods Observation of blood smears prepared from these animals revealed E. macaci infection rate of 42.7% in AGMs, 35% in Syke's monkeys and 33.3% in baboons. Results Gender infection rate was 38.2% in females and 29% in males. Statistically, there was no significant difference in infection rates between the monkey species and sexes (P > 0.05). Subsequent indirect immuno fluorescent antibody test supported the morphological appearance of E. macaci observed by microscopy. Sera from infected animals reacted positively (1:625) with E. macaci antigen, but not to Babesia bigemina or B. bovis antigen at 1:125 titer. Conclusion This study has revealed high prevalence of E. macaci infection in all three widely distributed Kenyan non-human primates. With the continued use of these animals as models for human parasitic diseases, the presence of this highly enzootic parasite should be noted.

关键词： C. mitis cercopithecus aethiops Entopolypoides macaci Kenya Papio cynocephalus anubis prevalence

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Despotic wild patas monkeys (Erythrocebus patas) in Kala Maloue, Cameroon

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AMERICAN JOURNAL OF PRIMATOLOGY 2008年第3期70卷 238-246页

作者： Nakagawa, Naofumi Kyoto Univ Sch Sci Human Evolut Studies Lab Dept ZoolDiv Biol SciGrad Sch Sci Kyoto 6068502 Japan

The socio-ecological model predicts that the quality, distribution, and patch size of food resources determines the dominance hierarchy of female monkeys based on the type of food competition they experience. Comparative studies of closely related species have evaluated the socio-ecological model and confirmed its validity. For example, female patas monkeys in Laikipia, Kenya, form a nonlinear and unstable dominance hierarchy (i.e., egalitarian), whereas females of sympatric, closely related savannah monkeys form a linear and stable dominance hierarchy (i.e., despotic), in accordance with the model's predictions of the characteristics of food resources. I compared agonistic interactions involving food between patas monkeys (Erythrocebus patas) and sympatric savannah monkeys (cercopithecus aethiops) in Kala Maloue, Cameroon. I found linear dominance hierarchies not only in savannah monkeys, but also in patas monkeys in Kala Maloue. The rates of agonistic interactions during feeding between patas monkeys were equivalent to those between savannah monkeys in Kala Maloue;further, these rates were significantly higher than those of both Laikipia patas and savannah monkeys. The results imply that patas monkeys in Kala Maloue are not egalitarian, but are despotic, similar to savannah monkeys. Disparity in the dominance hierarchies of patas monkeys between Kala Maloue and Laikipia were attributable to the differences in the characteristics of food resources. Although patas monkeys in Laikipia subsist on small and dispersed food resources within a high-density area, those in Kala Maloue subsisted on food resources that were clumped in intermediate-sized patches within a low-density area. This study shows that the socio-ecological model is applicable not only for interspecific comparisons but also for intraspecific comparisons.

关键词： agonistic interactions cercopithecus aethiops dominance Erythrocebus patas socio-ecology

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Physiologic manifestations of stress from capture and restraint of free-ranging male african green monkeys (cercopithecus aethiops)

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JOURNAL OF ZOO AND WILDLIFE MEDICINE 2004年第1期35卷 20-24页

作者： Suleman, MA Wango, E Sapolsky, RM Odongo, H Hau, J Natl Museums Kenya Inst Primate Res Nairobi Kenya Univ Nairobi Dept Anim Physiol Nairobi Kenya Stanford Univ Dept Sci Biol Stanford CA 94305 USA Univ Uppsala BMC Div Comparat Med S-75123 Uppsala Sweden

Adrenal gland weights, stomach mucosal lesions, and morning serum cortisol and prolactin levels were measured in 15 juvenile and adult male African green monkeys (cercopithecus aethiops) that were shot by a hunter, euthanized after 24 hr of captivity, or euthanized after 45 days of captivity and intermittent blood sampling. Hormone levels were measured in seven additional males that had been in captivity for 7 mo. Mean serum cortisol concentrations were significantly lower in free-ranging wild monkeys at the time they were shot than in the monkeys after 1 day in captivity. Cortisol concentrations were significantly higher in wild-caught monkeys on the day after capture than they were in the same animals after 18 and 26 days of captivity. Cortisol concentrations were also significantly higher in the wild-caught monkeys 18 days after capture than in the laboratory-habituated monkeys in captivity for 7 mo. Mean prolactin concentration was significantly lower in the wild-caught monkeys on day 2 after capture, and the levels increased gradually to 45 days in captivity and was highest in monkeys that had been captive for 7 mo.

关键词： prolactin hormone cortisol cercopithecus aethiops African green monkey stress

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Dopaminergic innervation of the pallidum in the normal state, in MPTP-treated monkeys and in parkinsonian patients

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European Journal of Neuroscience 2008年第12期12卷

作者： Caroline Jan Chantal François Dominique Tandé Jérôme Yelnik Léon Tremblay Yves Agid Etienne Hirsch INSERM U289 Mécanismes et Conséquences de la Mort Neuronale Hôpital de la Salpêtrière 47 Boulevard de l'Hôpital 75013 Paris France

The aim of the present study was to characterize the dopaminergic innervation of the pallidum in primates (humans and cercopithecus aethiops ). Firstly, in monkeys, biotin dextran amine was injected into dopaminergic areas, and the anterogradely labelled axons were reconstructed from serial sections and analysed in the pallidum. Secondly, in parkinsonian patients and MPTP-treated monkeys, the dopaminergic innervation of the pallidum was studied using tyrosine hydroxylase-positive fibre quantification. Our study revealed that dopaminergic areas A8 and A9 innervated the two pallidal segments. Individual axonal arborizations displayed a great heterogeneity. Some dopaminergic axons crossed the pallidum without branching, other axons made small terminal arborizations in a restricted region of one pallidal segment, whereas others developed dense arborizations covering extended areas in the two pallidal segments. This heterogeneous organization suggests that dopamine could directly modulate the pallidum using either a point-to-point or a diffuse projection pattern. A statistically significant loss of dopaminergic fibres in the internal (−43%) and external pallidum (−39.6%) of humans, and in the internal (−54.3%) and external pallidum (−59%) of monkeys was revealed in parkinsonian states. The consequences of this alteration are still unknown but it might participate in the triggering of motor symptoms observed in Parkinson's disease.

关键词： basal ganglia humans cercopithecus aethiops axonal tracing fibre quantification

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