Autonomous cage-side system for remote training of non-human primates.

BACKGROUND: Training non-human primates (NHPs) for translational medical experimentation is an essential yet time consuming process. To increase training efficiency, some training systems have been designed for NHPs to use at their home cages. Several autonomous cage-side tablet-based systems have been proposed, but none of these systems allow for remote monitoring and task modification while also being wireless, low-cost, light weight, and portable. NEW METHOD: Here we present ACTS: an Autonomous Cage-side Training System which meets all these criteria. ACTS consists of 1) a touchscreen tablet and a speaker attached to the subject's home cage, 2) an inexpensive reward system made from a slightly modified fish feeder, and 3), a laptop operating the system wirelessly and remotely via a router. RESULTS: We were able to test the system and wirelessly train two macaques in their home cages. Remote access enabled us to control ACTS from up to 90 m, through up to 3 walls, and through a floor of a building. The device is compatible with different reward pellet sizes and could run about two hours with a ∼4 mm pellet size. The animals were able to generalize the task when transferred to a traditional experimental rig. COMPARISON WITH EXISTING METHODS: The low cost and modest skill required to build and implement ACTS lowers the barrier for NHP researchers and caregivers to deploy autonomous, remotely controlled tablet-based cage-side systems. CONCLUSION: ACTS can be used for low-cost, wireless cage-side training of NHPs being prepared for translational medical experimentation.

Microbial structure and function in infant and juvenile rhesus macaques are primarily affected by age, not vaccination status.

Although thimerosal, an ethylmercury-based preservative, has been removed from most pediatric vaccines in the United States, some multidose vaccines, such as influenza vaccines, still contain thimerosal. Considering that a growing number of studies indicate involvement of the gut microbiome in infant immune development and vaccine responses, it is important to elucidate the impact of pediatric vaccines, including thimerosal-containing vaccines, on gut microbial structure and function. Here, a non-human primate model was utilized to assess how two vaccine schedules affect the gut microbiome in infants (5-9 days old) and juveniles (77-88 weeks old) through 16S ribosomal RNA sequencing and metabolomics analyses of the fecal samples. Two treatment groups (n = 12/group) followed either the vaccine schedule that was in place during the 1990s (intensive exposure to thimerosal) or an expanded schedule administered in 2008 (prenatal and postnatal exposure to thimerosal mainly via influenza vaccines), and were compared with a control group (n = 16) that received saline injections. The primary impact on gut microbial structure and function was age. Although a few statistically significant impacts of the two common pediatric vaccine schedules were observed when confounding factors were considered, the magnitude of the differences was small, and appeared to be positive with vaccination.

Examination of the safety of pediatric vaccine schedules in a non-human primate model: assessments of neurodevelopment, learning, and social behavior.

BACKGROUND: In the 1990s, the mercury-based preservative thimerosal was used in most pediatric vaccines. Although there are currently only two thimerosal-containing vaccines (TCVs) recommended for pediatric use, parental perceptions that vaccines pose safety concerns are affecting vaccination rates, particularly in light of the much expanded and more complex schedule in place today. OBJECTIVES: The objective of this study was to examine the safety of pediatric vaccine schedules in a non-human primate model. METHODS: We administered vaccines to six groups of infant male rhesus macaques (n = 12-16/group) using a standardized thimerosal dose where appropriate. Study groups included the recommended 1990s Pediatric vaccine schedule, an accelerated 1990s Primate schedule with or without the measles-mumps-rubella (MMR) vaccine, the MMR vaccine only, and the expanded 2008 schedule. We administered saline injections to age-matched control animals (n = 16). Infant development was assessed from birth to 12 months of age by examining the acquisition of neonatal reflexes, the development of object concept permanence (OCP), computerized tests of discrimination learning, and infant social behavior. Data were analyzed using analysis of variance, multilevel modeling, and survival analyses, where appropriate. RESULTS: We observed no group differences in the acquisition of OCP. During discrimination learning, animals receiving TCVs had improved performance on reversal testing, although some of these same animals showed poorer performance in subsequent learning-set testing. Analysis of social and nonsocial behaviors identified few instances of negative behaviors across the entire infancy period. Although some group differences in specific behaviors were reported at 2 months of age, by 12 months all infants, irrespective of vaccination status, had developed the typical repertoire of macaque behaviors. CONCLUSIONS: This comprehensive 5-year case-control study, which closely examined the effects of pediatric vaccines on early primate development, provided no consistent evidence of neurodevelopmental deficits or aberrant behavior in vaccinated animals.