Effects of Social Housing Changes on Immunity and Vaccine-Specific Immune Responses in Adolescent Male Rhesus Macaques

Abstract

Nonhuman primates (NHPs) in research institutions may be housed in a variety of social settings, such as group housing, pair housing or single housing based on the needs of studies. Furthermore, housing may change over the course of studies. The effects of housing and changes in housing on cell activation and vaccine mediated immune responses are not well documented. We hypothesized that animals moved indoors from group to single housing (GH-SH) would experience more stress than those separated from groups into pair housing (GH-PH), or those placed briefly into pair housing and separated 5 weeks later into single housing (GH-PH-SH). We also compared the effects of separation from group to pair housing with the separation from pair to single housing. Eighteen male rhesus macaques were followed over the course of changes in housing condition over 10-14 weeks, as well as prior to and after primary vaccination with a commercially available measles vaccine. We identified two phenotypic biomarkers, namely total CD8 population and proliferating B cells, that differed significantly across treatment groups over time. At 10 weeks post-separation, levels of proliferating B cells were higher in GH-SH subjects compared to GH-PH subjects, and in the latter, levels were lower at 10 weeks than prior to removal from group housing. At 2 weeks postseparation from group to single housing, the frequency of CD8+ T cells was higher in GH-SH subjects compared to one week post separation from pair into single housing in the GH-PH-SH subjects. Comparing the same elapsed time since the most recent separation activated CD20 populations were persistently higher in the GH-SH animals than the GH-PH-SH animals. Housing configuration did not influence vaccine-mediated responses. Overall, our study found benefits of pair housing over single housing, suggesting that perturbations in immune function will be more severe following separation from group to single housing than from pair to single housing, and supporting the use of short-duration pair housing even when animals must subsequently be separated. These findings are

Effect of single housing on innate immune activation in SIV-infected pigtail macaques (Macaca nemestrina) as a model of psychosocial stress in acute HIV infection

“…We acknowledge that this is a significant limitation of this study given that the complexity of social interactions in macaques can sometimes lead to individuals who experience greater stress from their social status than they would without contact with conspecifics ( 54 – 57 ). However, numerous publications have demonstrated the overall positive impact of social housing in comparison to single housing in diverse populations of macaques as assessed by both behavioral outcomes and immune function ( 53 , 58 – 60 ). One of these positive impacts is the phenomenon of social buffering.…”

“…Macaques are naturally social animals that require interaction with conspecifics to maintain their psychological welfare (49,50). This trait makes them a natural model to recapitulate psychosocial stress in a controlled setting, and multiple experimental designs have been used to validate the physiological and behavioral changes that occur in macaques under different social conditions (29,(51)(52)(53). Because this was a retrospective investigation, no stress biomarkers or behavioral assessments are available for the animals in this study.…”

Opportunities for Refinement of Non-Human Primate Vaccine Studies

“…In the opinion of these research teams, pair- and group-housed animals are more content, calmer, and may recover more quickly from procedures than singly housed animals on studies involving high containment pathogens. Social buffering studies (including in BSL-2) have shown the powerful role of social housing in mitigating reactions of NHPs to stressful events, enhancing immune responses, and optimizing the ability to cope with disease, potentially leading to models that are more representative of the human condition [ 13 , 40 , 41 , 42 , 43 , 44 , 45 ]. It is conceivable that working with calmer, less stressed subjects could also result in less variable data and more reproducible findings, which may enable a reduction in NHP use, though to our knowledge, this has not yet been proven in specifically designed studies.…”

Improving transparency—A call to include social housing information in biomedical research articles involving nonhuman primates

“…Interestingly, both stereotypic behaviors and SIB were associated with physiological consequences, including suggested malfunction of neurological loops connecting the cortex and the basal ganglia (Pomerantz et al, 2012), altered dopamine receptor levels in various brain regions (Freeman et al, 2015), and altered serotonin and opioid measures, in addition to changing responses to stress (see Tiefenbacher et al, 2005 for a review). The variation introduced by social housing conditions may be also be manifested in by additional outcome measures, including urinary cortisol (Hannibal et al, 2018), fecal cortisol and heart rate (Doyle et al, 2008), proliferating B cells (Pahar et al, 2020), neuroendocrine function (e.g., see review by Cacioppo et al, 2015), and the ratio of CD4 to CD8 lymphocytes (Schapiro et al, 2000). Furthermore, several serum biochemical and hematological parameters, such as blood urea nitrogen, glucose, alanine aminotransferase, and serum calcium concentrations, differed significantly between singly housed and socially housed cynomolgus macaques ( Macaca fascicularis ) (Koyama et al, 2018; Xie et al, 2014).…”