Bedding as an Enrichment Strategy in Group-housed Mauritian Cynomolgus Macaques (Macaca fascicularis).

The research community is committed to improving the well-being of nonhuman primates by providing opportunities to express species-specific behaviors such as foraging. In the wild, macaques spend a large part of their day foraging; this behavior is greatly limited in captivity. Bedding (wood shavings substrate) has been shown to promote foraging in rhesus macaques. However, the amount of bedding needed to affect these changes is unknown. Further, few studies have examined other benefits of bedding, including its potential to reduce noise levels, which can negatively impact welfare. We examined the use of bedding substrate in male Mauritius cynomolgus macaques (2-3-y-old) living in one of 2 social groups with either a full bale of bedding (that is, approximately 6 in of substrate) or a half bale (approximately 3 in) added to the pens for 10 d, followed by 4 d without bedding. We performed focal observations on 8 monkeys biweekly for 8 wk and used a dosimeter to measure sound in the room for 42 d. As expected, monkeys spent significantly more time foraging and less time self-grooming when bedding was present than when it was not. The amount of bedding did not make a difference. The presence of bedding did not affect social grooming or aggression, although it did help to dampen sound. Both peak and mean sound levels were lower with a full bale of bedding than with no bedding. Taken together, these results suggest that bedding is an effective enrichment strategy that can improve welfare of group-housed macaques.

A new group housing approach for non-human primate metabolism studies.

Understanding the absorption, distribution, metabolism and excretion (ADME) of candidate drugs in preclinical species is an integral part of the safety and efficacy evaluation in drug development. For this purpose, the housing of single animals in metabolism cages has historically been common practice for ADME studies. Whilst mini-pigs and dogs are selected wherever possible, non-human primates (NHPs) are used where there is no suitable scientific alternative. Having undergone only minimal revisions over the past 30 years, the traditional single-housing metabolism cage design for NHPs significantly limits normal vertical movement and social behaviours in primates. Minimising animal suffering and improving welfare is an important aspect of working with animals in research and Novo Nordisk A/S, together with collaborators, has focused on this area for many years. A novel metabolism cage for group housing of NHPs has been designed in a joint collaboration between Novo Nordisk A/S and Covance Inc. The advantages of this novel cage are extensive, including a significantly increased cage volume and ability for socialisation, as well as improvements to alleviate stress and boredom. The excretion balance data from six male NHPs housed in single or group metabolism cages were compared using the radiolabelled test compound [14C]-quetiapine. Welfare, in terms of stress and behaviour, when animals were single or group housed was also assessed. Mean recoveries of radioactivity were shown to be comparable irrespective of housing design (83.2% for group-housed animals vs. 87.1% for single-housed animals), supporting the potential suitability of NHP group housing for future metabolism ADME studies.

A novel welfare and scientific approach to conducting dog metabolism studies allowing dogs to be pair housed.

Metabolism cages are designed to conduct absorption, distribution, metabolism and excretion (ADME) studies, enabling an 'excretion balance' scientific objective to be met. Historically, the design of dog metabolism cages has involved single housing. This type of housing has limitations for normal social behaviours and has been largely unchanged for 25-30 years. Improving animal welfare is a focus area for the authorities as well as the industry throughout the European Union. A collaboration was developed between Novo Nordisk and Covance to enhance the design of metabolism cages, allowing dogs to be pair housed. The purpose of the study was to compare excretion balance data from pair-housed and singly housed dogs in order to demonstrate that conducting excretion balance studies with a pair-housing design improves animal welfare without compromising the scientific integrity of the study. A radiolabelled test compound, [14C]-Quetiapine, was selected for this investigation based on its excretion profile. The assessment of the dogs' stress levels was investigated by measuring the levels of serum cortisol as an indicative biomarker. Results were inconclusive due to large variations in cortisol levels. However, dogs appeared calmer in the pair-housing setting. The overall mean recovery (±standard deviation) for pair-housed animals (94.0 ± 0.66% of the dose) was equivalent to that from singly housed dogs (93.0 ± 2.29%). Based on these data, we conclude that pair housing of dogs for future metabolism ADME studies does not compromise the scientific integrity, and therefore is a major progression in the design of these studies, enhancing welfare.

Development of standard operating procedures to obtain longitudinal vaginal specimens from nulliparous rabbits as part of HIV vaccine mucosal immunogenicity studies.

The New Zealand white rabbit model (Oryctolagus cuniculus) is widely used to test whether HIV vaccine candidates elicit systemic antibody responses; however, its use in mucosal immunology has not been fully exploited due to the difficulty in collecting mucosal specimens longitudinally and reproducibly. Here we describe feasible and non-feasible methods to collect vaginal and nasal specimens from nulliparous rabbits. Non-feasible methods were those resulting in poor reproducibility and considerable animal twitching during sampling, whereas feasible methods resulted in no animal twitching and potential for sampling reproducibility. Standard operating procedures (SOPs) were implemented to collect vaginal swabs yielding total IgA titres ranging from 12,500 to 312,500. Intranasal immunisation with a naked DNA vaccine encoding HIV gp140 elicited HIV envelope-specific IgA detectable in nasal but not in vaginal secretions. Our methods provide an alternative to reliably assess pre- and post-vaccination mucosal antibody titres longitudinally in rabbits as part of mucosal HIV vaccine immunogenicity studies.

A mouse model for ricin poisoning and for evaluating protective effects of antiricin antibodies.

UNLABELLED: BACKGROUND. Ricin is a potential bioterrorism agent and no specific antidote or treatment exists for ricin poisoning. For this reason, we developed ricin-specific antibodies that were tested in a murine model of ricin poisoning for use as antidotes against symptoms of ricin poisoning. METHODS: Mice were poisoned with a lethal dose of ricin (5 microg) and their temperature and general condition were monitored for determination of a surrogate and humane end point. Mice were then treated with injections of ricin and different combinations of polyclonal anti-ricin antibodies. Antibody effect was evaluated for various doses and using various time points from ricin to antibody injection. Also, the effect of adjuvant symptomatic treatment was examined. Brain, heart, intestines, kidney, liver, lung, pancreas, spleen, and stomach tissues were sampled for histopathological analysis. RESULTS: The mouse model was reproducible and easy to use. A clear protective effect of both anti-ricin A-chain and anti-ricin B-chain antibodies-but not of irrelevant antibodies-was demonstrated with no added effect of symptomatic treatment. CONCLUSIONS: These data suggest that specific polyclonal antibodies against ricin A- and B-chain may reproducibly protect mice against ricin poisoning, even when the antibodies are administered up to 1.5 h after poisoning.