Maternal Immunization with Adjuvanted Recombinant Receptor-Binding Domain Protein Provides Immune Protection against SARS-CoV-2 in Infant Monkeys.

Maternal vaccinations administered prior to conception or during pregnancy enhance the immune protection of newborn infants against many pathogens. A feasibility experiment was conducted to determine if monkeys can be used to model the placental transfer of maternal antibody against SARS-CoV-2. Six adult rhesus monkeys were immunized with adjuvanted recombinant-protein antigens comprised of receptor-binding domain human IgG1-Fc fusion proteins (RBD-Fc) containing protein sequences from the ancestral-Wuhan or Gamma variants.

Prognostic Performance of Hematological and Serum Iron and Metabolite Indices for Detection of Early Iron Deficiency Induced Metabolic Brain Dysfunction in Infant Rhesus Monkeys.

Background: The current pediatric practice of monitoring for infantile iron deficiency (ID) via hemoglobin (Hgb) screening at one y of age does not identify preanemic ID nor protect against later neurocognitive deficits.

Objectives: To identify biomarkers of iron-related metabolic alterations in the serum and brain and determine the sensitivity of conventional iron and heme indices for predicting risk of brain metabolic dysfunction using a nonhuman primate model of infantile ID.

Methods: Simultaneous serum iron and RBC indices, and serum and cerebrospinal fluid (CSF) metabolomic profiles were determined in 20 rhesus infants, comparing iron sufficient (IS; N = 10) and ID (N = 10) infants at 2 and 4 mo of age.

Significant Microbial Changes Are Evident in the Reproductive Tract of Pregnant Rhesus Monkeys at Mid-Gestation but Their Gut Microbiome Does Not Shift until Late Gestation.

Vaginal and rectal specimens were obtained from cycling, pregnant, and nursing rhesus monkeys to assess pregnancy-related changes in the commensal bacteria in their reproductive and intestinal tracts. Using 16S rRNA gene amplicon sequencing, significant differences were found only in the vagina at mid-gestation, not in the hindgut. To verify the apparent stability in gut bacterial composition at mid-gestation, the experiment was repeated with additional monkeys, and similar results were found with both 16S rRNA gene amplicon and metagenomic sequencing.

Effects of anesthesia exposure on postnatal maturation of white matter in rhesus monkeys.

There is increasing concern about the potential effects of anesthesia exposure on the developing brain. The effects of relatively brief anesthesia exposures used repeatedly to acquire serial magnetic resonance imaging scans could be examined prospectively in rhesus macaques. We analyzed magnetic resonance diffusion tensor imaging (DTI) of 32 rhesus macaques (14 females, 18 males) aged 2 weeks to 36 months to assess postnatal white matter (WM) maturation.

Reticulocyte Hemoglobin Equivalent has Comparable Predictive Accuracy as Conventional Serum Iron Indices for Predicting Iron Deficiency and Anemia in a Nonhuman Primate model of Infantile Iron Deficiency.

Background: Infantile iron deficiency (ID) causes anemia and compromises neurodevelopment. Current screening relies on hemoglobin (Hgb) determination at 1 year of age, which lacks sensitivity and specificity for timely detection of infantile ID. Low reticulocyte Hgb equivalent (RET-He) indicates ID, but its predictive accuracy relative to conventional serum iron indices is unknown.

Tandem mass tag proteomic and untargeted metabolomic profiling reveals altered serum and CSF biochemical datasets in iron deficient monkeys.

The effects of early-life iron deficiency anemia (IDA) extend past the blood and include both short- and long-term adverse effects on many tissues including the brain. Prior to IDA, iron deficiency (ID) can cause similar tissue effects, but a sensitive biomarker of iron-dependent brain health is lacking. To determine serum and CSF biomarkers of ID-induced metabolic dysfunction we performed proteomic and metabolomic analysis of serum and CSF at 4- and 6- months from a nonhuman primate model of infantile IDA.

Multiomic profiling of iron-deficient infant monkeys reveals alterations in neurologically important biochemicals in serum and cerebrospinal fluid before the onset of anemia.

The effects of iron deficiency (ID) during infancy extend beyond the hematologic compartment and include short- and long-term adverse effects on many tissues including the brain. However, sensitive biomarkers of iron-dependent brain health are lacking in humans. To determine whether serum and cerebrospinal fluid (CSF) biomarkers of ID-induced metabolic dysfunction are concordant in the pre/early anemic stage of ID before anemia in a nonhuman primate model of infantile iron deficiency anemia (IDA).

Lyticase Facilitates Mycobiome Resolution Without Disrupting Microbiome Fidelity in Primates.

Background: Microbiome research has expanded to consider contributions of microbial kingdoms beyond bacteria, including fungi (i.e., the mycobiome).

Proteobacteria abundance during nursing predicts physical growth and brain volume at one year of age in young rhesus monkeys.

Over the last decade, multiple studies have highlighted the essential role of gut microbiota in normal infant development. However, the sensitive periods during which gut bacteria are established and become associated with physical growth and maturation of the brain are still poorly defined. This study tracked the assembly of the intestinal microbiota during the initial nursing period, and changes in community structure after transitioning to solid food in infant rhesus monkeys (Macaca mulatta).

Correcting iron deficiency anemia with iron dextran alters the serum metabolomic profile of the infant Rhesus Monkey.

Background: The effects of infantile iron deficiency anemia (IDA) extend beyond hematological indices and include short- and long-term adverse effects on multiple cells and tissues. IDA is associated with an abnormal serum metabolomic profile, characterized by altered hepatic metabolism, lowered NAD flux, increased nucleoside levels, and a reduction in circulating dopamine levels.

Objectives: The objective of this study was to determine whether the serum metabolomic profile is normalized after rapid correction of IDA using iron dextran injections.

Infantile Iron Deficiency Affects Brain Development in Monkeys Even After Treatment of Anemia.

A high percent of oxidative energy metabolism is needed to support brain growth during infancy. Unhealthy diets and limited nutrition, as well as other environmental insults, can compromise these essential developmental processes. In particular, iron deficiency anemia (IDA) has been found to undermine both normal brain growth and neurobehavioral development.

Gut Microbial and Metabolic Profiling Reveal the Lingering Effects of Infantile Iron Deficiency Unless Treated with Iron.

Scope: Iron deficiency (ID) compromises the health of infants worldwide. Although readily treated with iron, concerns remain about the persistence of some effects. Metabolic and gut microbial consequences of infantile ID were investigated in juvenile monkeys after natural recovery (pID) from iron deficiency or post-treatment with iron dextran and B vitamins (pID+Fe).

General anaesthesia during infancy reduces white matter micro-organisation in developing rhesus monkeys.

Background: Non-human primates are commonly used in neuroimaging research for which general anaesthesia or sedation is typically required for data acquisition. In this analysis, the cumulative effects of exposure to ketamine, Telazol® (tiletamine and zolazepam), and the inhaled anaesthetic isoflurane on early brain development were evaluated in two independent cohorts of typically developing rhesus macaques.

Methods: Diffusion MRI scans were analysed from 43 rhesus macaques (20 females and 23 males) at either 12 or 18 months of age from two separate primate colonies.

Maternal determinants of gestation length in the rhesus monkey.

A gestation length of normal duration and natural delivery at term are considered to be important indicators of a healthy pregnancy, especially given the potentially adverse consequences for neonates of being born premature. While many have assessed the factors influencing gestation length in humans, and there has been considerable interest in the pregnancy duration of domesticated farm animals, this topic has not been re-assessed recently in rhesus monkeys, the most commonly used primate in biomedical research. In older articles, it's gestation length was typically reported to be 165 days, although most authors acknowledged that viable pregnancies could occur out to 180 days.

Effects of Iron Deficiency Anemia and Its Rapid Correction on the Serum Metabolomic Profile of Rhesus Infants.

Objectives: To determine whether rapid correction of iron deficiency using intramuscular iron dextran normalizes serum metabolomic changes in a nonhuman primate model of iron deficiency anemia (IDA).

Methods: Blood was collected from naturally iron-sufficient (IS;  = 10) and IDA ( = 12) male and female infant rhesus monkeys () at 6 months of age. IDA infants were treated with intramuscular injections of iron dextran, 10 mg/weekly for 4-8 weeks.

Transgenerational propensities for infant birth weight reflect fetal growth history of the mother in rhesus monkeys.

Birth weight (BW) at delivery is an important developmental milestone indicative of prenatal conditions and portends of the postnatal growth trajectory that will occur during infancy and childhood. Previous research has documented that there are also many physiological and health consequences of being born either small-for-gestational age (SGA) or large-for-gestational age (LGA). Analyses of breeding animals have demonstrated further that a gravid female exerts a strong influence on the size of her infant by term, and this permissiveness or constraint over fetal growth can be transmitted from mothers to their daughters.

Feasibility of successfully breeding rhesus macaques (Macaca mulatta) to obtain healthy infants year-round.

Rhesus monkeys are typically seasonal breeders but can be induced to extend the timing of their mating and births under captive conditions. The following analyses evaluated the potential impact of extending their pregnancies and deliveries year-round. Birth records from a large breeding colony housed in an indoor facility with a constant 14-hr light/10-hr dark cycle were analyzed across 25 years to examine seasonal trends in monkeys that mated in one of two ways: spontaneous in social groups or with a scheduled, timed-mating protocol.

Early-Life Iron Deficiency and Its Natural Resolution Are Associated with Altered Serum Metabolomic Profiles in Infant Rhesus Monkeys.

Background: Iron deficiency is the most common nutrient deficiency in human infants aged 6 to 24 mo, and negatively affects many cellular metabolic processes, including energy production, electron transport, and oxidative degradation of toxins. There can be persistent influences on long-term metabolic health beyond its acute effects.

Objectives: The objective was to determine how iron deficiency in infancy alters the serum metabolomic profile and to test whether these effects persist after the resolution of iron deficiency in a nonhuman primate model of spontaneous iron deficiency.

Maternal and Breast Milk Influences on the Infant Gut Microbiome, Enteric Health and Growth Outcomes of Rhesus Monkeys.

Objectives: Gut bacteria play an essential role during infancy and are strongly influenced by the mode of birth and feeding. A primate model was used to investigate the benefits of exposure to the mother or conversely the negative impact of early nursery rearing on microbial colonization.

Method: Rectal swabs were obtained from rhesus macaques born vaginally and mother-reared (MR, N = 35) or delivered primarily via cesarean-section and human-reared (HR, N = 19).

Postcranial Skeletal Differences in Free-Range and Captive-Born Primates.

Skeletal morphology is important in evolutionary, genetic, developmental, physiological, and functional studies. Although samples from free-ranging individuals may be preferable, constraints of sample size, demography, or conservation status may necessitate the inclusion of captive-born individuals. Captivity may be associated with physical, physiological, or behavioral differences that may affect skeletal form.

Low Lactobacilli abundance and polymicrobial diversity in the lower reproductive tract of female rhesus monkeys do not compromise their reproductive success.

The lower reproductive tract of nonhuman primates is colonized with a diverse microbiota, resembling bacterial vaginosis (BV), a gynecological condition associated with negative reproductive outcomes in women. Our 4 aims were to: (i) assess the prevalence of low Lactobacilli and a BV-like profile in female rhesus monkeys; (ii) quantify cytokines in their cervicovaginal fluid (CVF); (iii) examine the composition and structure of their mucosal microbiota with culture-independent sequencing methods; and (iv) evaluate the potential influence on reproductive success. CVF specimens were obtained from 27 female rhesus monkeys for Gram's staining, and to determine acidity (pH), and quantify proinflammatory cytokines.

The UNC-Wisconsin Rhesus Macaque Neurodevelopment Database: A Structural MRI and DTI Database of Early Postnatal Development.

Rhesus macaques are commonly used as a translational animal model in neuroimaging and neurodevelopmental research. In this report, we present longitudinal data from both structural and diffusion MRI images generated on a cohort of 34 typically developing monkeys from 2 weeks to 36 months of age. All images have been manually skull stripped and are being made freely available via an online repository for use by the research community.

Social Influences on Prevotella and the Gut Microbiome of Young Monkeys.

Objective: Our aim was to evaluate the bacterial profiles of young monkeys as they were weaned into peer groups with a particular focus on Prevotella, an important taxon in both human and nonhuman primates. The weaning of infants and increased social contact with peers is a developmental stage that is likely to affect the gut microbiome.

Methods: Gut bacteria were assessed in 63 rhesus monkeys living in social groups comprised of 4 to 7 individuals.

Metabolomic analysis of CSF indicates brain metabolic impairment precedes hematological indices of anemia in the iron-deficient infant monkey.

Objectives: Iron deficiency (ID) anemia leads to long-term neurodevelopmental deficits by altering iron-dependent brain metabolism. The objective of the study was to determine if ID induces metabolomic abnormalities in the cerebrospinal fluid (CSF) in the pre-anemic stage and to ascertain the aspects of abnormal brain metabolism affected.

Methods: Standard hematological parameters [hemoglobin (Hgb), mean corpuscular volume (MCV), transferrin (Tf) saturation, and zinc protoporphyrin/heme (ZnPP/H)] were compared at 2, 4, 6, 8, and 12 months in iron-sufficient (IS; n = 7) and iron-deficient (ID; n = 7) infant rhesus monkeys.

Gestational Timing of Prenatal Disturbance and Fetal Sex Determine the Developmental Outcomes.

Background: Maternal stress during pregnancy can have deleterious consequences, increasing risk for prematurity and low birth weight, as well as postnatal effects on emotional regulation and neuromotor development. It is less clear, however, whether moderate and brief gestational disturbances have similar effects.

Objective: To determine the impact of a delimited period of moderate maternal stress on infant growth, emotional reactivity, and neurobehavioral maturity in a nonhuman primate model.