Increased mucosal CD4+ T cell activation in rhesus macaques following vaccination with an adenoviral vector.

UNLABELLED: The possibility that vaccination with adenovirus (AdV) vectors increased mucosal T cell activation remains a central hypothesis to explain the potential enhancement of HIV acquisition within the Step trial. Modeling this within rhesus macaques is complicated because human adenoviruses, including human adenovirus type 5 (HAdV-5), are not endogenous to macaques. Here, we tested whether vaccination with a rhesus macaque-derived adenoviral vector (simian adenovirus 7 [SAdV-7]) enhances mucosal T cell activation within rhesus macaques. Following intramuscular SAdV-7 vaccination, we observed a pronounced increase in SAdV-7-specific CD4(+) T cell responses in peripheral blood and, more dramatically, in rectal mucosa tissue. Vaccination also induced a significant increase in the frequency of activated memory CD4(+) T cells in SAdV-7- and HAdV-5-vaccinated animals in the rectal mucosa but not in peripheral blood. These fluctuations within the rectal mucosa were also associated with a pronounced decrease in the relative frequency of naive resting CD4(+) T cells. Together, these results indicate that peripheral vaccination with an AdV vector can increase the activation of mucosal CD4(+) T cells, potentially providing an experimental model to further evaluate the role of host-vector interactions in increased HIV acquisition after AdV vector vaccination. IMPORTANCE: The possibility that vaccination with a human adenovirus 5 vector increased mucosal T cell activation remains a central hypothesis to explain the potential enhancement of human immunodeficiency virus (HIV) acquisition within the Step trial. In this study, we tested whether vaccination with a rhesus macaque-derived adenoviral vector in rhesus macaques enhances mucosal CD4(+) T cell activation, the main cell target of simian immunodeficiency virus (SIV)/HIV. The results showed that vaccination with an adenoviral vector indeed increases activation of mucosal CD4(+) T cells and potentially increases susceptibility to SIV infection.

Cognitive Dissonance in Laboratory Animal Medicine and Implications for Animal Welfare.

People experience cognitive dissonance when they entertain 2 conflicting ideas at the same time. Cognitive dissonance may cause a negative emotional state, which can lead to engagement of compensation mechanisms to resolve the conflict. Here we describe a survey that explores cognitive dissonance in laboratory animal veterinarians and veterinary technicians and various ways in which veterinary staff manage dissonance associated with research animal use. Respondents-164 veterinarians and 145 veterinary technicians-were asked to rate their opinions of various statements on a sliding scale of 'strongly disagree' to 'strongly agree' or 'never' to 'always.' Statements assessed negative emotions (discomfort, powerlessness, frustration) and compensation mechanisms (devaluing, emotional distancing, shifting responsibility) as bases for inferring effects on welfare states of animals. Responses were evaluated overall and were compared according to level of training (veterinarian compared with veterinary technician), years of work experience (0 to 5, 6 to 10, greater than 10), and species tended (large, mixed, small species). Respondents strongly agreed that animal wellbeing and animal use in research were important. Respondents reported feelings of discomfort, powerlessness, and frustration associated with work. In addition, respondents reported feeling empowered to initiate changes affecting animal welfare. The most frequent compensation mechanism noted was shifting responsibility onto the IACUC and institutional rules. Devaluing the animals was another reported compensation mechanism. Responses to emotional distancing statements were divided. Survey responses supported the existence of cognitive dissonance associated with laboratory animal medicine. Potential negative and positive effects on animal welfare are discussed.

Hepatic Hemangiosarcoma in a Cynomolgus Macaque (Macaca fascicularis).

An experimentally naïve, 9-y-old, intact male cynomolgus macaque was reported for bleeding from an unidentified site. Sedated physical examination indicated mild gingival separation from the lingual aspect of the upper right canine tooth as the source of the hemorrhage. Physical exam revealed a firm mass adhered to the left zygomatic arch, 2 subcutaneous nodules on the chest, and a large mass in the cranial abdomen. Radiographs revealed a large soft-tissue mass in the cranial abdomen and multifocal nodules in the caudal lung fields. On ultrasonography, the liver was grossly enlarged and contained a cavi- tated mass. Hematology and serum chemistry results demonstrated severe regenerative anemia with normal clotting times and adequate platelet count. For humane reasons, euthanasia was elected. On gross examination, the liver was markedly enlarged by an expansile mass primarily affecting the median lobe, with multiple, smaller nodules throughout the remaining lobes. Multifocal round, firm nodules were observed on the surface of all lung lobes and throughout the omentum. Histologic examination of the hepatic, cutaneous, osseous, and pulmonary lesions demonstrated well-defined, endothelium-lined vascular channels arranged in cords with abundant hemorrhage; endothelial-cell immunomarkers confirmed these results. On the basis of these findings, hepatic hemangiosarcoma, with metastases to the lungs, omentum, subcutis, and bone, was diagnosed. This case study is the first report of spontaneous hepatic hemangiosarcoma in a cynomolgus macaque and the first case with metastasis to bone in a NHP.

Using a Cageside Device for Testing Glycosylated Hemoglobin in Cynomolgus Macaques (Macaca fascicularis).

Nonhuman primates naturally develop type 2 diabetes mellitus and exhibit clinical features that are similar to those observed in humans, including obesity, insulin resistance, dyslipidemia, and pancreatic pathology. The glycosylated hemoglobin (HbA1C) test is the primary test used for diabetes management in humans because it reflects the average blood glucose levels over the previous 3 mo. The HbA1C results are a better predictor of potential risk of complications than are single or episodic measures of glucose levels. HbA1C levels have proven useful for the diagnosis and monitoring of blood glucose levels in NHP, but for testing by a commercial laboratory, the test requires a vial of whole blood, results are not available for several days, and the test is expensive. The cageside device requires a single drop of blood, it displays the HbA1C percentage in 5 min, and the cost per sample is less than for sending it to a commercial lab. We therefore assessed the correlation between a cageside test using a handheld unit and the commercial lab test for measuring HbA1C in cynomolgus macaques. From both normal and confirmed diabetic animals, 4 mL blood was collected from a peripheral vessel and sent to a commercial lab for HbA1C testing. At the same time, a drop of capillary blood was collected and tested immediately in the HbA1C cageside test. A comparison of the results revealed significant correlation between the cageside and commercial lab tests. Therefore, we feel that the HbA1C test using handheld device may help to rule out nondiabetics and indicate which animals require additional testing.

Neurocysticercosis in a Rhesus Macaque (Macaca mulatta).

An 8-y-old, intact, male rhesus macaque (Macaca mulatta) was sedated to undergo MRI in preparation for the implantation of cranial hardware. During imaging, 9 focal lesions were noted in the brain and musculature of the head. The lesions were hyperechoic with hypoechoic rims. The animal was deemed inappropriate for neuroscience research, and euthanasia was elected. Gross examination revealed multiple round, thick-walled, fluid-filled cysts (diameter, approximately 0.5 cm) in multiple tissues: one each in the left caudal lung lobe, left masseter muscle, and the dura overlying the brain and 8 throughout the gray and white matter of the brain parenchyma. Formalin-fixed sections of cyst-containing brain were stained with hematoxylin and eosin. Microscopic examination and molecular analysis of the COX1 (COI) gene recognized the causative organism as Taenia solium at 99.04% identity.

Recent refinements to cranial implants for rhesus macaques (Macaca mulatta).

The advent of cranial implants revolutionized primate neurophysiological research because they allow researchers to stably record neural activity from monkeys during active behavior. Cranial implants have improved over the years since their introduction, but chronic implants still increase the risk for medical complications including bacterial contamination and resultant infection, chronic inflammation, bone and tissue loss and complications related to the use of dental acrylic. These complications can lead to implant failure and early termination of study protocols. In an effort to reduce complications, we describe several refinements that have helped us improve cranial implants and the wellbeing of implanted primates.

Injury related to environmental enrichment in a dog (Canis familiaris): gastric foreign body.

A pregnant 7-y-old Beagle crossbred dog (Canis familiaris) presented with clinical signs of lethargy, dehydration, and occasional vomiting. The dog was managed with fluids, antibiotics, and supportive care for several days in an effort to maintain the pregnancy. The bitch aborted the pups at approximately 50 d of gestation and was euthanized due to her poor reproductive performance and age. Necropsy revealed a compact mass of plastic pieces in the pylorus of the stomach. The gastric foreign body was discovered to be the vinyl covering of a bed that was in the dog's run as part of the environmental enrichment program for this animal. The use of that type of dog bed was discontinued. This case emphasizes that any type of enrichment can cause harm and the risks must be assessed carefully before implementing any enrichment device.

Positive reinforcement training to enhance the voluntary movement of group-housed sooty mangabeys (Cercocebus atys atys).

Positive reinforcement training (PRT) has successfully been used to train diverse species to execute behaviors helpful in the everyday care and wellbeing of the animals. Because little information is available about training sooty mangabeys (Cercocebus atys atys), we analyzed PRT with a group of 30 adult males as they were trained to shift from 1 side of their enclosure to the other. Over a 4-mo period we conducted 57 training sessions totaling 26.5 h of training and recorded compliance information. During training, compliance increased from 76% of the animals during the first 5 training sessions to 86% of the animals shifting during the last 5 sessions. This result indicated progress but fell short of our goal of 90% compliance. After 25 training sessions, problem-solving techniques were applied to help the consistently noncompliant animals become more proficient. The techniques included reducing social stress by shifting animals so that noncompliant monkeys could shift into an unoccupied space, using more highly preferred foods, and 'jackpot'-sized reinforcement. To determine whether social rank affected training success, animals were categorized into high, medium, and low dominance groups, based on 7 h of behavioral observations. A Kruskal-Wallis test result indicated a significant difference in compliance according to the category of dominance. Although training a group this large proved challenging, the mangabeys cooperated more than 90% of the time during follow-up sessions. The training program improved efficiency in caring for the mangabeys.