Chlorocebus Aethiops Sabaeus Research Articles

Spontaneous Hypertension and Cardiorenal Pathologies in the African Green Monkey

The African Green monkey (AGM), Chlorocebus aethiops sabaeus, is a highly translational non‐human primate model of spontaneous hypertension. Using forearm plethysmography under ketamine sedation (~15mg/kg), AGMs were categorized as hypertensive (HT, SBP >140mmHg), borderline hypertensive (BHT, 120mmHg < SBP < 140mmHg), or normotensive (NT, SBP < 120 mmHg). Of the 264 animals phenotyped, 32% (85 of 264) were HT (average MAP 108.2±2.2mmHg), 18% (49 of 264) were BHT (average MAP 87.5±2.0mmHg), and 49% (130 of 264) were NT (average MAP 68.6±1.3mmHg). HT animals tend to be older than NT animals (12.4±0.7 yrs vs. 8.7±0.6 yrs; p<0.05) with elevated heart rates (134.3±2.1 bpm vs. 121.6±1.9 bpm, p<0.05), similar to human essential hypertension. HT animals have increased cellular myocyte cross‐sectional area in left ventricles (1658.4±194.7 μm2) compared to NT (791.0±168.9 μm2;p<0.05, n=8) AGMs. Wall/lumen (W/L) ratios of renal arterioles (>100µm diameter) were greater in HT (0.15±0.02 vs. 0.11±0.04; p<0.05, n=8) animals. HT glomeruli have increased Bowman's capsular space (44.4±3.1% area vs. 30.9±1.9% area; p<0.05, n=5). Elevated heart rates and left ventricular hypertrophy suggest that hypertension in AGMs is driven by increased sympathetic nerve activity (SNA). Increased W/L ratios and Bowman's capsular space indicate renal vascular remodeling and altered glomerular function. This data postulates that the AGM is a model of spontaneous hypertension with elevated SNA, increased renal vascular resistance and altered glomerular capillary function. Supported by Biomedical Sciences Research Group, LLC and the Behavioural Sciences Foundation

Long‐term Telemetric Blood Pressure Measurement in a Translational Model of Non‐human Primate Spontaneous Hypertension

A non‐human primate model of spontaneous hypertension has potential for understanding mechanisms of cardiovascular disease but requires a novel method for telemetric blood pressure measurement. Stellar Telemetry solid‐state pressure sensors were surgically implanted into the abdominal aorta of feral, male monkeys (Chlorocebus aethiops sabaeus). Systolic (SBP), diastolic (DBP) and mean (MBP) arterial pressures, core body temperature and heart rate were determined using different data acquisition parameters to assess system precision and reliability in this physically active non‐human primate. Animals were pre‐phenotyped for normotension (NT) or hypertension (HT) using forearm plethysmography. Various recording parameters yielded consistent blood pressure in NT (MBP=104±4.35 mmHg) and HT (MBP=126±7.57 mmHg) animals. Ultrasonography documented effective placement of sensors within the aorta lumen. Consistent aortic blood pressure recordings were obtained for 6 months post catheter implantation. Necropsy revealed no sensor induced blood or organ pathologies. The Stellar Telemetry system effectively monitors conscious blood pressure, heart rate and body temperature in active primates allowing for physiological assessments during natural social interactions and species specific behaviors. This model of hypertension in an old world, non‐human primate is translational to human essential hypertension and allows for new directions in a genetically similar species.Supported by Biomedical Sciences Research Group, LLC; TSE Systems, Inc.; Behavioural Sciences Foundation

Resistance of Klebsiella pneumoniae to the innate immune system of African green monkeys

In recent years, an emergent Klebsiella pneumoniae hypermucoviscosity (HMV) phenotype has been associated with increased invasiveness and pathogenicity in primates. In this project, bacteria recovered from infected African green monkeys (AGM) (Chlorocebus aethiops sabaeus) were screened for HMV phenotype, and were compared to non-HMV isolates in in vitro, serum, and oxidative-mediated killing assays. Complement-mediated killing was assessed utilizing freshly collected serum from healthy AGM. Oxidative-mediated killing was investigated utilizing sodium hypochlorite and hydrogen peroxide. Compared to non-HMV isolates, HMV isolates were more resistant to serum-mediated and oxidative killing (p<0.05). Phagocytosis resistance was evaluated using AGM peripheral blood monocytes (PBMC), and results indicated that non-HMV isolates associated with the AGM PBMC to a greater extent than HMV isolates (p<0.001). Measurement of lactate dehydrogenase release showed that HMV isolates were more cytotoxic to AGM PBMC than non-HMV isolates (p<0.001). Thus, the hypermucoid phenotype appears to be an important virulence factor that promotes evasion of innate immune defenses.

Abstract 412: A Unique Telemetric Method for Long-term Measurement of Blood Pressures and Core Body Temperature in Hypertensive and Normotensive Non-human Primates

A non-human primate model of essential hypertension has unequivocal potential for understanding mechanisms of disease but requires a unique method for telemetric blood pressure measurement in animals living within a habituated natural environment. We have now identified a unique non-human primate model of spontaneous, essential hypertension in Chlorocebus aethiops sabaeus, the African Green, or vervet, monkey. Using forearm plethysmography under light ketamine sedation (~15mg/kg), adult vervets were categorized as hypertensive (HT; SBP &gt;140mmHg), borderline hypertensive (BHT; 120mmHg &lt; SBP &lt; 140mmHg), or normotensive (NT; SBP &lt; 120 mmHg). Of the 168 males phenotyped, 32% (53 of 168) were HT (average SBP = 168.79±3.29mmHg), 27% (45 of 168) were BHT (average SBP = 129.58±0.88mmHg), and 41% (70 of 168) were NT (average SBP = 100.21±1.65mmHg). Stellar Telemetry solid-state pressure sensors were surgically implanted into the abdominal aorta of feral, male monkeys (Chlorocebus sabaeus aethiops). SBP, diastolic (DBP) and mean (MBP) arterial pressures, core body temperature and heart rate were determined using different data acquisition parameters to assess system precision and reliability in this physically active non-human primate with spontaneous essential hypertension. All animals were pre-phenotyped for blood pressure using forearm plethysmography under light ketamine anesthesia. Different recording parameters (n=4) yielded consistent BPs, in normotensive (MBP=104±4.35 mmHg) and hypertensive (MBP=126±7.57 mmHg) animals. Ultrasonographic examination documented effective sensor placement directly within the vessel lumen. Post implant necropsy revealed no sensor induced blood pathologies. Conscious, telemetered SBPs were consistent with those of monkeys measured using plethysmography. This model of hypertension in an Old World, non-human primate is translational to human essential hypertension and allows for new directions in a genetically similar species. The use of the Stellar Telemetry system is ideal for monitoring conscious blood pressure, heart rate and body temperature in active primates allowing for cardiovascular assessment during natural social interactions and species specific behaviors.

The Hair-Diet13C and15N Fractionation inChlorocebus aethiops sabaeusBased on a Control Diet Study

Understanding the 13C and 15N enrichments between primate diet and hair is necessary for reconstructing primate diets and ecology. However, dietary lipids need to be controlled for in order to accurately estimate the hair 13C and 15N enrichment factors (e*). We report diet-hair 13C and 15N enrichment factors for vervet monkeys (Chlorocebus aethiops sabaeus) based on a controlled diet study in captivity. The vervet monkeys were fed a standard monkey chow exclusively. The 13Ce*hair-diet and 15Ne*hair-diet values for male adults were 2.8‰ and 2.9‰, respectively; those for lactating females were 2.4‰ and 2.2‰, respectively. The isotope enrichment between hair from infant (ca. 3 months of age) and hair from its mother were 13Ce*hair(infant-mother) and 15Ne* and 15Ne* hair(infant-mother) were 0.7‰ and 1.8‰, respectively.

Circadian measurement of blood pressures and core body temperature in conscious, freely moving vervet monkeys (LB857)

A non‐human primate model of essential hypertension has excellent potential for understanding mechanisms of disease. Blood pressure (systolic, SBP; diastolic, mean; MBP), heart rate and core body temperature was measured in freely moving, mature Chlorocebus aethiops sabaeus (African green monkey; vervet) by telemetry (Stellar Telemetry; TSE Systems Inc.). Stellar Telemetry solid‐state pressure sensors were placed in the abdominal aorta of feral, male monkeys. 24 hour SBP, diastolic and MBP, core body temperature and heart rate were determined using different data acquisition parameters to assess system precision and reliability. Different recording parameters (n=4) yielded consistent BPs, in normotensive (MBP=104±4.35 mmHg) and hypertensive (MBP=126±7.57 mmHg) animals. Ultrasonographic examination documented effective placement of sensors within the vessel lumen. Post implant necropsy revealed no sensor induced blood pathologies. SBPs were consistent with those of monkeys measured using plethysmography. This model of hypertension in an Old World, non‐human primate is translational to human essential hypertension and allows for new directions in a genetically similar species. The use of the Stellar Telemetry system is ideal for monitoring conscious blood pressure, heart rate and body temperature in active primates to allow for natural social interactions and species‐specific behavior

Spontaneous essential hypertension in the non‐human primate Chlorocebus aethiops sabaeus, the African green monkey (1136.16)

Current models of essential hypertension have limited comparisons to humans due to differences in posture and periods of activity. The annual cycle of spontaneous hypertension in male Chlorocebus aethiops sabaeus was assessed in an outbred research colony. Using plethysmography, systolic (SBP) and diastolic blood pressures (DBP) of adult male African Green, or vervet, monkeys (n=163) were measured in May/June after ketamine sedation (~10‐15mg/kg). Blood pressure phenotypes were characterized as hypertensive (HT: SBP 蠅 140mmHg) or normotensive (NT: SBP 蠄 120mmHg). SBP and DBP identified 33% (n=53) HT (average SBP 169.04±24.19mmHg) and 41% NT (average SBP 101.32 ±13.28mmHg, n=66) animals. Borderline hypertension (BHT) was identified with an average SBP of 129.09±5.85mmHg (n=44). A randomized group of animals (n=51) were re‐measured in September/October. HT monkeys (n=21) decreased blood pressure from 174.14±27.48mmHg to 128.61±28.48mmHg (p&lt;0.05). SBPs of NT (n=21) and BHT animals (n=9) were unchanged (p&gt;0.05). A third of adult male vervet monkeys in this colony exhibit spontaneous hypertension with unique seasonal variation compared to NT or BHT animals. This model of hypertension in an Old World non‐human primate is highly translational to human essential hypertension and allows for new research directions in a novel genetically similar species.Grant Funding Source: Supported by Behavioural Science Foundation

Orchidectomy does not significantly affect spine synapse density in the CA3 hippocampal subfield in St. Kitts vervet monkeys (Chlorocebus aethiops sabaeus)

Gonadal hormones induce significant changes in cognitive function, associated with alterations in the structure of the hippocampus. We have previously shown that androgens increase the number of spine synapses in the CA1 stratum radiatum of the monkey hippocampus. Recent evidence, however, suggests that loss of testicular hormone production may have variable effects on neuroplasticity in different regions of the hippocampus. To test this hypothesis, we examined the effects of orchidectomy in the dentate gyrus and CA3 subfield of the hippocampus in male St. Kitts vervet monkeys (Chlorocebus aethiops sabaeus). Spine synapse density was significantly reduced (39%) after orchidectomy in the dentate gyrus, consistent with previously published reports in CA1 (40%). However, in CA3 orchidectomy induced a much smaller (22%) reduction in synapse density, which did not reach the limits of statistical significance. These results suggest that orchidectomy exerts heterogeneous effects on hippocampal spine synapse density, the CA3 subfield being relatively spared compared to CA1 and the dentate gyrus. This heterogeneity may contribute to the mixed functional responses observed in males following loss of testicular hormone secretions.

Significant Genotype by Diet (G × D) Interaction Effects on Cardiometabolic Responses to a Pedigree‐Wide, Dietary Challenge in Vervet Monkeys (Chlorocebus aethiops sabaeus)

Nutrient composition of a diet (D) has been shown to interact with genetic predispositions (G) to affect various lipid phenotypes. Our aim in this study was to confirm G × D interaction and determine whether the interaction extends to other cardiometabolic risk factors such as glycemic measures and body weight. Subjects were vervet monkeys (Chlorocebus aethiops sabaeus; n = 309) from a multigenerational pedigreed colony initially fed with a plant-based diet, standard primate diet (18% calories from protein, 13% from fat, and 69% from carbohydrates), and subsequently challenged for 8 weeks with a diet modeled on the typical American diet (18% calories from protein, 35% from fat, and 47% from carbohydrates). Our results showed that although exposure to the challenge diet did not result in significant changes in weight, most lipid and glycemic biomarkers moved in an adverse direction (P < 0.01). Quantitative genetic analyses showed that cardiometabolic phenotypes were significantly heritable under both dietary conditions (P < 0.05), and there was significant evidence of G × D interaction for these phenotypes. We observed significant differences in the additive genetic variances for most lipid phenotypes (P < 10(-4) ), indicating that the magnitude of genetic effects varies by diet. Furthermore, genetic correlations between diets differed significantly from 1 with respect to insulin, body weight, and some lipid phenotypes (P < 0.01). This implied that distinct genetic effects are involved in the regulation of these phenotypes under the two dietary conditions. These G × D effects confirm and extend previous observations in baboons (Papio sp.) and suggest that mimicking the typical human nutritional environment can reveal genetic influences that might not be observed in animals consuming standard, plant-based diets.

25(OH)D3and Cardiovascular Risk Factors in Female Nonhuman Primates

To determine if interindividual differences in plasma concentrations of 25-hydroxyvitamin D(3) (25(OH)D(3)) have pathophysiologic significance, we evaluated a cohort of female monkeys, seeking to identify associations with clinically relevant cardiovascular risk factors, including age, abdominal obesity (waist circumference), and high-density lipoprotein cholesterol (HDL-C). One hundred fifty-five female vervet monkeys (Chlorocebus aethiops sabaeus) aged 3-25 years consumed a typical western diet for 7-8 weeks that provided a woman's equivalent of approximately 1000 IU/day of vitamin D(3). Measurements of vitamin D(3) and HDL-C concentrations, as well as waist circumference, were obtained. Among young monkeys (aged 3-5 years), compared to older monkeys (aged 16-25 years), the mean plasma 25(OH)D(3) concentrations were 82.3±3.2 ng/mL and 58.6±2.9 ng/mL (p<0.0001), respectively. Plasma 25(OH)D(3) concentrations had a range of 19.6-142.0 ng/mL (mean±standard error [SE] 66.4±1.7 ng/mL). 25(OH)D(3) concentrations were inversely associated with age (p<0.0001) and waist circumference (p=0.016) and were positively correlated with HDL-C (p=0.01). However, when statistically controlling for age, none of these relationships remained significant. Higher plasma concentrations of 25(OH)D(3) were associated with more favorable cardiovascular risk factors, with inverse associations observed between 25(OH)D(3) and abdominal obesity, HDL-C, and age. These associations were no longer significant when controlling for age.

PHENOTYPIC AND GENOTYPIC CHARACTERIZATION OF KLEBSIELLA PNEUMONIAE ISOLATES RECOVERED FROM NONHUMAN PRIMATES

Klebsiella pneumoniae is a zoonotic, Gram-negative member of the family Enterobacteriaceae and is the causative agent of nosocomial septicemic, pneumonic, and urinary tract infections. Recently, pathogenic strains of K. pneumoniae sharing a hypermucoviscosity (HMV) phenotype have been attributed to multisystemic abscessation in both human and nonhuman primates. Although K. pneumoniae is a well-recognized zoonotic agent, there is a lack of general information including adequate diagnostic methods or treatments for nonhuman primates. In an effort to increase the body of knowledge of this enigmatic pathogen, K. pneumoniae isolates from African green monkeys (Chlorocebus aethiops sabaeus) on the island of St. Kitts, West Indies were genotypically and phenotypically characterized. Genetic fingerprints generated by PCR-mediated genomic fingerprinting, phenotypic characterization, and antimicrobial susceptibility all identified a high degree of similarity between the HMV and non-HMV K. pneumoniae isolates. The results obtained from this work will help establish a baseline for the development of efficacious diagnostic methods and treatment strategies for both human and nonhuman primates.

A non-human primate system for large-scale genetic studies of complex traits.

Non-human primates provide genetic model systems biologically intermediate between humans and other mammalian model organisms. Populations of Caribbean vervet monkeys (Chlorocebus aethiops sabaeus) are genetically homogeneous and large enough to permit well-powered genetic mapping studies of quantitative traits relevant to human health, including expression quantitative trait loci (eQTL). Previous transcriptome-wide investigation in an extended vervet pedigree identified 29 heritable transcripts for which levels of expression in peripheral blood correlate strongly with expression levels in the brain. Quantitative trait linkage analysis using 261 microsatellite markers identified significant (n = 8) and suggestive (n = 4) linkages for 12 of these transcripts, including both cis- and trans-eQTL. Seven transcripts, located on different chromosomes, showed maximum linkage to markers in a single region of vervet chromosome 9; this observation suggests the possibility of a master trans-regulator locus in this region. For one cis-eQTL (at B3GALTL, beta-1,3-glucosyltransferase), we conducted follow-up single nucleotide polymorphism genotyping and fine-scale association analysis in a sample of unrelated Caribbean vervets, localizing this eQTL to a region of <200 kb. These results suggest the value of pedigree and population samples of the Caribbean vervet for linkage and association mapping studies of quantitative traits. The imminent whole genome sequencing of many of these vervet samples will enhance the power of such investigations by providing a comprehensive catalog of genetic variation.

Delayed match-to-sample performance in African green monkeys (Chlorocebus aethiops sabaeus)

Delayed match-to-sample (DMTS) procedures are among the most commonly used attention and memory tasks in behavioral pharmacology and have been utilized in a variety of species. Although macaque species such as the rhesus and cynomolgus macaque are often used for such studies, availability and disease transmission raise concerns over their use. The present study investigated whether the African green monkey might function as a suitable alternative by evaluating operant performance on a DMTS task and comparing this species' response to some commonly used drugs (0.025-0.075 mg/kg physostigmine, 0.0033-0.03 mg/kg scopolamine, 0.014-0.44 mg/kg atropine, 0.125-1.0 mg/kg midazolam, and 0.125-2.0 mg/kg diazepam) to the responses previously reported in macaques. Results demonstrated that African green monkeys are capable of learning and performing a DMTS task, and dose-effect functions for behavioral pharmacology were quite similar to those reported for rhesus macaques and other nonhuman primate species. Thus, the African green monkey may function as a suitable alternative to macaque species in behavioral pharmacology research.

Serum lipid levels influence cognitive performance in older vervet monkeys (Chlorocebus aethiops sabaeus) on a long‐term stable diet

Epidemiological data indicate high comorbidity between diseases linked to serum lipid levels, such as atherosclerosis, and cognitive decline. However, it is difficult to reduce the effects of poor general lifestyle to specific mechanisms that can produce these deficits. Here we used an animal model to determine the relation between serum lipids and cognitive decline in a population whose diet was stable across the lifespan. Serum lipids and cognitive performance were assessed in 61 African Green Monkeys, ranging in age from 3–24 years and maintained on a standard diet (high fiber, low fat, high protein) over the lifespan; female subjects were not pregnant at sampling. Learning and response inhibition were measured using a visual discrimination/reversal task. For those animals in the highest quintile for age (17–24 years), serum low density lipids were negatively associated and serum high density lipids were positively correlated with cognitive performance on all indices tested (p &lt;0.05). These relationships were not evident for younger subjects. Thus, the relation between serum lipids and cognitive performance is not independent of age and is present in individuals who maintain a healthy diet across the lifespan. Research supported by P40 RR019963, RL1 MH 083270, UL1‐DE019580.

Planum temporale grey matter asymmetries in chimpanzees (Pan troglodytes), vervet (Chlorocebus aethiops sabaeus), rhesus (Macaca mulatta) and bonnet (Macaca radiata) monkeys

Brain asymmetries, particularly asymmetries within regions associated with language, have been suggested as a key difference between humans and our nearest ancestors. These regions include the planum temporale (PT) – the bank of tissue that lies posterior to Heschl's gyrus and encompasses Wernicke's area, an important brain region involved in language and speech in the human brain. In the human brain, both the surface area and the grey matter volume of the PT are larger in the left compared to right hemisphere, particularly among right-handed individuals. Here we compared the grey matter volume and asymmetry of the PT in chimpanzees and three other species of nonhuman primate in two Genera including vervet monkeys (Chlorocebus aethiops sabaeus), rhesus macaques (Macaca mulatta) and bonnet macaques (Macaca radiata). We show that the three monkey species do not show population-level asymmetries in this region whereas the chimpanzees do, suggesting that the evolutionary brain development that gave rise to PT asymmetry occurred after our split with the monkey species, but before our split with the chimpanzees.

A novelty seeking phenotype is related to chronic hypothalamic-pituitary-adrenal activity reflected by hair cortisol

Reduced hypothalamic pituitary adrenal (HPA) activity is associated with greater novelty seeking in humans. Hair cortisol represents an integrated proxy measure of total cortisol production/release over an extended period of time and may be a valuable tool for tracking the HPA system. Sampling approaches (collection of blood, saliva, urine, or feces) for socially housed nonhuman primates present a number of technical challenges for collection particularly when repeated sampling is necessary. Herein we describe a relationship between cortisol levels measured in hair collected from 230 socially housed female vervet ( Chlorocebus aethiops sabaeus) monkeys and a free-choice novelty seeking phenotype. A predator-like object was placed at the periphery of the outdoor enclosures for 30 min and speed of approach (latency to approach within 1 m) and persistence of interest (number of 1 min intervals within 1 m) were scored. A composite Novelty Seeking score, combining these two measures, was calculated. The intra-class correlation coefficient (ICC = .68) for two different objects across years indicated that this score reflects a stable aspect of temperament. Hair samples were collected from each subject approximately 3–6 months following the second assessment; cortisol levels were determined from the hair. A significant inverse relationship of Novelty Seeking score with hair cortisol level (p < .01) was noted. The high hair cortisol groups had significantly lower Novelty Seeking scores than the low cortisol groups both years (p's < .05). These results suggest that low average cortisol levels promote novelty seeking, while high average levels inhibit novelty seeking behavior.

Chromosomal Dynamics in Cercopithecini Studied by Williams-Beuren probe mapping

Abstract Chromosomal evolution in the tribe Cercopithecini and in related taxa is highly debated. Uncertainty in reconstruction is mainly related to the great genetic variability and polymorphism of the taxa. Recent molecular and karyological efforts individuate a split between genetically conservative, arbitrarily defined, “terrestrial” guenons and vervets, and genetically variable and derived “arboreal” guenons. We performed the mapping of WS loci probe (7q11.23) in order to verify the chromosomal dynamics of the genomes of three tree-dwelling species of the tribe: C. neglectus, C. mitis mitis, C. albogularis labiatus. Data from literature for the “ground-dwelling” Chlorocebus aethiops sabaeus has been compared with our results. The distribution of the WS probe showed a high genomic dynamics in the different species, with three different pattern of rearrangements. Starting from the ancestral synteny 7 found in Pongo pygmaeus (PPY), the present mapping demonstrates different location of the hybridization...

Prevalence of Hypermucoid Klebsiella pneumoniae among Wild-caught and Captive Vervet Monkeys (Chlorocebus aethiops sabaeus) on the Island of St. Kitts

Invasive, hypermucoid Klebsiella pneumoniae causes severe abscess formation in humans and in certain species of nonhuman primates. We conducted a survey of captive and wild-caught African green monkeys, or vervets (Chlorocebus aethiops sabaeus), on the Caribbean island of St. Kitts to assess their carriage rate of Klebsiella spp. Forty percent of rectal swabs from captive monkeys were positive for K. pneumoniae, and 20% of wild-caught animals were positive. Two wild-caught monkeys (4%) were positive for K. oxytoca, and one monkey (2%) was found to be infected with a hypermucoid rmpA-positive K. pneumoniae strain. Genotyping of this strain showed that it had an indistinguishable random amplified polymorphic DNA fingerprint to a strain that caused fatal abscessation in several African green monkeys in a research colony in the USA in 2005. This is the first report of hypermucoid K. pneumoniae isolation from a wild population of nonhuman primates and represents a potential health risk to these animals, as well as to the humans who come in contact with them.

Clinicopathologic Characterization of Naturally Occurring Diabetes Mellitus in Vervet Monkeys

Diabetes mellitus (DM) is a group of chronic metabolic diseases characterized by persistent fasting hyperglycemia, and it can be of either polygenic or monogenic origin. Animal models have played an important role in elucidating the pathophysiology of the polygenic Type 1 and type 2 DM forms; however, useful animal models of the monogenic forms do not exist. The authors describe 4 cases of naturally occurring DM in vervet monkeys (Chlorocebus aethiops sabaeus), 1 of which has clinicopathologic findings consistent with type 2 DM, including persistent hyperglycemia, hypertriglyceridemia, islet amyloidosis, and reduced islet insulin immunostaining. In contrast, the 3 remaining animals have clinicopathologic similarities to a monogenic form of the disease, including a lack of islet amyloidosis and hypertriglyceridemia, as well as normal islet insulin immunostaining. In addition, pedigree analysis conducted on one of these animals is consistent with either an autosomal dominant or mitochondrial inheritance pattern, which supports a monogenic form of DM. The authors thus hypothesize that a naturally occurring monogenic form of diabetes may occur in vervet monkeys, making them a potential animal model for future studies.

Immunogenicity and some safety features of a VEGF-based cancer therapeutic vaccine in rats, rabbits and non-human primates

We have developed a cancer vaccine candidate (hereafter denominated CIGB-247), based on recombinant modified human vascular endothelial growth factor (VEGF) as antigen, and the adjuvant VSSP (very small sized proteoliposomes of Neisseria meningitidis outer membrane). In mice, previous work of our group had shown that vaccination with CIGB-247 extended tumor-take time, slowed tumor growth, and increased animal survival. Immunization elicited anti-human and murine VEGF-neutralizing antibodies, and spleen cells of vaccinated mice are cytotoxic in vitro to tumor cells that produce VEGF. We have now tested the immunogenicity of CIGB-247 in Wistar rats, New Zealand White rabbits and the non-human primate Chlorocebus aethiops sabaeus. Using weekly, biweekly and biweekly plus montanide immunization schemes, all three species develop antigen-specific IgG antibodies that can block the interaction of VEGF and VEGF receptor 2 in an ELISA assay. Antibody titers decline after vaccination stops, but can be boosted with new immunizations. In monkeys, DTH and direct cell cytotoxicity experiments suggest that specific T-cell responses are elicited by vaccination. Immunization with CIGB-247 had no effect on normal behavior, hematology, blood biochemistry and histology of critical organs, in the tested animals. Skin deep wound healing was not affected in vaccinated rats and monkeys.