The mammalian gastrointestinal tract harbors a highly diverse and dynamic community of bacteria. The array of this gut bacterial community, which functions collectively as a fully unified organ in the host metabolism, varies greatly among different host species and can be shaped by long-term nutritional interventions. Non-human primates, our close phylogenetic relatives and ancestors, provide an excellent model for studying diet-microbiome interaction; however, compared to clinical and rodent studies, research targeting primate gut microbiome has been limited. Herein, we analyze the gut microbiome composition in female cynomolgus macaques (Macaca fascicularis; n = 20) after the long-term (2.5 years) consumption of diets designed to mimic recent human Western- (WD; n = 10) or Mediterranean-type (MD; n = 10) diets. Microbiome diversity in MD consumers was significantly higher by the Shannon diversity index compared to the WD consumers, with similar but non-significant trends noted for the diversity metrics of species richness (Chao 1), observed operational taxonomic units (OTUs) and phylogenetic diversity (PD) whole Tree. Compared to the MD, the WD group demonstrated a higher Firmicutes-Bacteroides ratio and a significantly higher abundance of families Clostridiacea and Lactobacillaceae. Further analyses reveal significantly higher abundance of genera Lactobacillus, Clostridium, Faecalibacterium, and Oscillospira and lower abundance of Ruminococcus and Coprococcus in MD consumers relative to WD consumers. OTUs belonging to several species also show significant differences between the two groups, with Lactobacillus species demonstrating a prominently higher abundance in the MD consumers. The data reveal several differences in the gut microbiome of primates consuming the two different diets and should be useful for further studies aimed at understanding the diet-microbiome-health interactions in primates.

Objective This study aimed to determine the effects of humanlike Western and Mediterranean diets on caloric intake, obesity, metabolism, and hepatosteatosis in an established nonhuman primate model of obesity, cardiometabolic syndrome, type 2 diabetes, and atherosclerosis. Methods A 38‐month, randomized, preclinical, nonhuman primate primary prevention trial of 38 socially housed, middle‐aged adult females was conducted. The monkeys were characterized during a 7‐month baseline phase while consuming chow and then randomized to either Western or Mediterranean diets; the groups were balanced on baseline characteristics. Western and Mediterranean diets were formulated to closely reflect human diets, matched on macronutrient content, with protein and fat derived largely from animal sources in the Western diet and plant sources in the Mediterranean diet. Food consumption, activity levels, energy expenditure, body composition, carbohydrate metabolism, and hepatosteatosis were measured during baseline and treatment phases. Results The Western diet increased caloric intake for the first 6 months and body fat, activity, energy expenditure, insulin resistance, and hepatosteatosis after 2.5 years, whereas the Mediterranean diet reduced triglyceride levels. Conclusions This is the first report of differential caloric intake and obesity with long‐term consumption of a Western versus Mediterranean diet under controlled experimental conditions and the first experimental evidence that a Mediterranean diet protects against hepatosteatosis compared with a Western diet.

The SARS-CoV-2 pandemic has affected more than 185 million people worldwide resulting in over 4 million deaths. To contain the pandemic, there is a continued need for safe vaccines that provide durable protection at low and scalable doses and are easily delivered. Here, AAVCOVID-1, an adeno-associated viral (AAV), Spike gene-based vaccine candidate demonstrates potent immunogenicity in mouse and nonhuman primates following a single injection and confers complete protection from SARS-CoV-2 challenge in macaques. Peak neutralizing antibody titers are sustained at 1 year and complemented by functional memory T-cell responses. The AAVCOVID vector has no relevant pre-existing immunity in humans, does not elicit cross-reactivity to common AAVs used in gene therapy, and its persistence and expression wanes following injection. The single, low dose requirement, high yield manufacturability, and 1-month stability for storage at room-temperature may make this technology well-suited to support effective immunization campaigns for emerging pathogens on a global scale.

SARS-CoV-2 variants have emerged with enhanced pathogenicity and transmissibility, and escape from pre-existing immunity, suggesting first-generation vaccines and monoclonal antibodies may now be less effective. Here we present an approach for preventing clinical sequelae and the spread of SARS-CoV-2 variants. First, we affinity matured an angiotensin-converting enzyme 2 (ACE2) decoy protein, achieving 1000-fold binding improvements that extend across a wide range of SARS-CoV-2 variants and distantly related, ACE2-dependent coronaviruses. Next, we demonstrated the expression of this decoy in proximal airway when delivered via intranasal administration of an AAV vector. This intervention significantly diminished clinical and pathologic consequences of SARS-CoV-2 challenge in a mouse model and achieved therapeutic levels of decoy expression at the surface of proximal airways when delivered intranasally to nonhuman primates. Importantly, this long-lasting, passive protection approach is applicable in vulnerable populations such as the elderly and immune-compromised that do not respond well to traditional vaccination. This approach could be useful in combating COVID-19 surges caused by SARS-CoV-2 variants and should be considered as a countermeasure to future pandemics caused by one of the many pre-emergent, ACE2-dependent CoVs that are poised for zoonosis.

Heart disease is an increasingly recognized, serious late effect of radiation exposure, most notably among breast cancer and Hodgkin’s disease survivors, as well as the Hiroshima and Nagasaki atomic bomb survivors. The purpose of this study was to evaluate the late effects of total-body irradiation (TBI) on cardiac morphology, function and selected circulating biomarkers in a well-established nonhuman primate model. For this study we used male rhesus macaques that were exposed to a single total-body dose of ionizing gamma radiation (6.5–8.4 Gy) 5.6–9.7 years earlier at ages ranging from ~3–10 years old and a cohort of nonirradiated controls. Transthoracic echocardiography was performed annually for 3 years on 20 irradiated and 11 control animals. Myocardium was examined grossly and histologically, and myocardial fibrosis/collagen was assessed microscopically and by morphometric analysis of Masson’s trichrome-stained sections. Serum/plasma from 27 irradiated and 13 control animals was evaluated for circulating biomarkers of cardiac damage [N-terminal pro B-type natriuretic protein (nt-proBNP) and troponin-I], inflammation (CRP, IL-6, MCP-1, sICAM) and microbial translocation [LPS-binding protein (LBP) and sCD14]. A higher prevalence of histological myocardial fibrosis was observed in the hearts obtained from the irradiated animals (9/14) relative to controls (0/3) (P = 0.04, χ2). Echocardiographically determined left ventricular end diastolic and systolic diameters were significantly smaller in irradiated animals (repeated measures ANOVA, P < 0.001 and P < 0.008, respectively). Histomorphometric analysis of trichrome-stained sections of heart tissue demonstrated ~14.9 ± 1.4% (mean ± SEM) of myocardial area staining for collagen in irradiated animals compared to 9.1 ± 0.9 % in control animals. Circulating levels of MCP-1 and LBP were significantly higher in irradiated animals (P < 0.05). A high incidence of diabetes in the irradiated animals was associated with higher plasma triglyceride and lower HDLc but did not appear to be associated with cardiovascular phenotypes. These results demonstrate that single total-body doses of 6.5–8.4 Gy produced long-term effects including a high incidence of myocardial fibrosis, reduced left ventricular diameter and elevated systemic inflammation. Additional prospective studies are required to define the time course and mechanisms underlying radiation-induced heart disease in this model.