Safety and Immunogenicity Study of a Bivalent Vaccine for Combined Prophylaxis of COVID-19 and Influenza in Non-Human Primates.

Background: Influenza and SARS-CoV-2 viruses are two highly variable pathogens. We have developed a candidate bivalent live vaccine based on the strain of licensed A/Leningrad/17-based cold-adapted live attenuated influenza vaccine (LAIV) of H3N2 subtype, which expressed SARS-CoV-2 immunogenic T-cell epitopes. A cassette encoding fragments of S and N proteins of SARS-CoV-2 was inserted into the influenza NA gene using the P2A autocleavage site.

A spontaneous hyperglycaemic cynomolgus monkey presents cognitive deficits, neurological dysfunction and cataract.

Chronic hyperglycaemia is a chief feature of diabetes mellitus and complicates with many systematic anomalies. Non-human primates (NHPs) are excellent for studying hyperglycaemia or diabetes and associated comorbidities, but lack behavioural observation. In the study, behavioural, brain imaging and histological analysis were performed in a case of spontaneously hyperglycaemic (HGM) Macaca fascicularis.

Markers of antroponotic viral infections in vervet monkeys arrived from their natural habitat (Tanzania).

Introduction: Various human viruses have been identified in wild monkeys and in captive primates. Cases of transmission of viruses from wild monkeys to humans and vice versa are known. The aim of this study was to identify markers of anthroponotic viral infections in vervet monkeys ( ) arrived from their natural habitat (Tanzania).

[Indicators of spontaneous behavior of rhesus monkeys with short-term course alcohol self-administration under free choice].

Objective: To analyze spontaneous behavior in 36 male rhesus macaques during formation of alcoholic motivation under free choice.

Material And Methods: The model composed the initiation stage with the provision of an aqueous ethanol solution of increasing concentration from 1 to 4% with a sweetener and restricted access to the tap water supply and the subsequent stage of the formation of alcoholic motivation with a free choice between 4% ethanol solution without sweetener and water. The behavior was recorded by the «One-Zero» method with ethogram compiled in accordance with the behavioral peculiarities of rhesus monkeys when housed individually.

Individual Features of the Hypothalamic-Pituitary-Thyroid Axis Functioning during Aging in Non-Human Primates.

Individual features of age-related changes in the function of the neuroendocrine systems are an important problem as the basic component of a personalized approach to predicting and treating age-related pathologies. We studied the age-related features of the function of the hypothalamic-pituitary-thyroid axis in laboratory primates with depression- and anxiety-like behavior (DAB). It was found that in young female rhesus monkeys with DAB, the basal and thyrotropin-releasing hormone-stimulated levels of thyroid-stimulating hormone were significantly lower than in young animals with standard behavior (control).

Genotyping of Macaque Population on the Brain-Derived Neurotrophic Factor Gene Polymorphism by Mismatch Amplification Mutation Assay (MAMA)-PCR.

Human rs6265 (196G>A) polymorphism in the BDNF gene is associated with many clinically significant phenotypic manifestations. Rhesus monkey (Macaca mulatta) has a functionally significant rs309950446 ( 136G>A) polymorphism. To determine this polymorphism in macaques, we used mismatch amplification mutation assay (MAMA)-PCR method with non-complementary nucleotide to the template chain at the 3rd position from the 3'-end of the allele-specific primers (mismatch primers), which allowed the best discrimination of the alleles.

Analysis of the Ability to Skill Formation and Stability of the Formed Skill in Mature Male Rhesus Monkeys (Macaca mulatta) and Hamadryas Baboons (Papio hamadryas).

A comparative study of the ability to form a skill, the dynamics of its formation, and repeatability in sexually mature male rhesus monkeys (Macaca mulatta) and hamadryas baboons (Papio hamadryas) was carried out. It was found that male hamadryas baboons of the study group demonstrate higher learning ability, training level, and repeatability of the formed skill compared to the studied male rhesus monkeys. At the same time, animals of both species demonstrated similar dynamics of skill formation.

Clearance and Utilization of Dicarbonyl-Modified LDL in Monkeys and Humans.

The kinetics of elimination of various dicarbonyl-modified low-density lipoproteins from the bloodstream of monkeys were investigated. The low-density lipoproteins (LDL) in the monkey blood plasma were isolated by density gradient ultracentrifugation and labeled in vitro with the fluorescent dye FITC; thereupon, they were modified with different natural low molecular-weight dicarbonyls: malondialdehyde (MDA), glyoxal, or methylglyoxal. The control native FITC-labeled LDL and dicarbonyl-modified FITC-labeled LDL were injected into the monkey's ulnar vein; thereafter, blood samples were taken at fixed time intervals during 24 h.

Comparability of biosimilar romiplostim with originator: Protein characterization, animal pharmacodynamics and pharmacokinetics.

The results of preclinical studies of romiplostim analogue GP40141 are presented. The effect of a cell proliferation, phosphorylation of the TPO receptor and JAK2 phosphorylation were studied in the presence of romiplostim and in the presence of GP40141 in a cell line of mice (Mus musculus) lymphoblasts with stable expression of human TPO receptor 32D-hTPOR clone 63. Binding to the TPO receptor and to the neonatal Fc receptor (FcRn) was examined for both romiplostim and the developed analogue.

Age-Related Changes in the Clustering of Blood Populations in Cynomolgus Monkeys Depend on Sex and Immune Status.

Non-anthropoid primates cynomolgus monkeys (), also known as crab-eating macaques, are increasingly used in biomedical and preclinical studies due to their evolutionary proximity to humans, sharing similar diets, infectious and senile diseases. Age-related changes and sexual dimorphism of the immune system of C. monkeys have not been sufficiently characterized in literature, though age and sex differences affect the course of diseases and sensitivity to medications.

Composition of Bacteriophages for Therapeutic and Prophylactic Use in Monkeys.

Keeping rhesus monkeys as laboratory animals requires timely prevention and treatment of infections, including diseases of bacterial etiology. Based on our own studies of the microflora of healthy and sick monkeys, as well as analysis of published reports, we identified clinically significant representatives of pathogenic and opportunistic bacteria: E. coli, Staphylococcus aureus, Klebsiella spp.

Age-related and individual features of the HPA axis stress responsiveness under constant light in nonhuman primates.

The hypothalamic-pituitary-adrenal (HPA) axis is a key adaptive neuroendocrine system, dysfunction of which plays an important role in the increasing incidence of stress-dependent age-related pathology. Among the environmental factors effecting increase age-related diseases, great importance is given to disturbances of the light-dark schedule, particularly with increased illumination at night. While disruption of the light-dark schedule has long been recognized as a powerful behavioral stressor, little is known regarding stress reactivity of the HPA under constant light (CL) conditions, especially with aging and depending on the features of stress behavior.

Antigenotoxic and antimutagenic effects of lignin derivative BP-C2 against dioxidine and cyclophosphamide in vivo in murine cells.

The study investigated antigenotoxic and antimutagenic activity of novel lignin-derived polyphenolic composition (BP-C2) with ammonium molybdate towards cyclophosphamide and dioxidine in the bone marrow, blood and liver cells of BALB/c mice. BP-C2 was given to mice via gavage at 60, 80 and 120 mg/kg once 1 h before single intraperitoneal injection of a genotoxic agent. 1.

Measles in non-human primates.

It is six decades since the measles vaccine was first introduced, and yet we continue to see frequent outbreaks of this disease occurring all over the world. Many non-human primate (NHP) species, including apes, are susceptible to the measles virus. Spontaneous measles outbreaks have been described in a number of zoos and primate centers worldwide.

Effects of Combined Treatment with Compounds Affecting Mitochondria on Physiological Parameters in Old Monkey.

Correction of mitochondrial function is a promising direction for modulating aging processes. The effect of NAD (in the form of its precursor nicotinamide mononucleotide, NMN) and antioxidant MitoQ specifically affecting mitochondria was studied on male rhesus monkeys (Macaca mulatta). The first group of animals initially received only NMN, the second group received only MitoQ, and then both groups received both drugs simultaneously.

Inflammatory and autoimmune predictive markers of response to anti-PD-1/PD-L1 therapy in NSCLC and melanoma.

Immune checkpoint inhibitors (ICI) are a standard in cancer therapy, but few patients respond to the treatment. The aim of the present study was the determination of immunological markers for monitoring response to ICI. The present study included 74 patients receiving ICI in subsequent [group 1; non-small cell lung cancer (NSCLC)] and first-line setting (group 2; melanoma) and 30 patients with NSCLC receiving first-line chemotherapy.

[Enteral viral hepatitis in monkeys].

Within the last decade, a large number of viruses genetically related to human hepatitis viruses have been identified in different animal species, including monkeys. Numerous viruses related to human hepatitis A virus (HAV, Picornaviridae: Hepatovirus: Hepatovirus A) were detected in various mammalian species in 2015-2018, predominantly in bats and rodents, but also in shrews, seals and marsupials. Zoonotic hepatitis E virus (HEV, Hepeviridae: Orthohepevirus: Orthohepevirus A) genotypes have been found in wild boars, deer, camels, and rabbits, as well as in non human primates.

[Comparative analysis of residual neurovirulence of vaccine and low attenuated rubella virus (Matonaviridae: Rubivirus: Rubella virus) strains in the experiments on the macaque rhesus (Macaca mulatta) monkeys].

Introduction: Rubella is currently an infection controlled by specific prophylaxis. Not only the right vaccine prophylaxis strategy and tactics, but also the use of effective and safe vaccine preparations is crucial for the elimination of this disease.The aim of the investigation was to study the morphological and pathogenetic patterns of changes developing in the central nervous system (CNS) and internal organs of monkeys (Haplorhini) during intracerebral inoculation with 2 strains of rubella virus (Matonaviridae: Rubivirus: Rubella virus) (RV): highly attenuated Orlov-B, and low attenuated Orlov-14.

Seasonal Variability of Biochemical Parameters in Female Cynomolgus Macaques (Macaca fascicularis).

We study of seasonal variability of biochemical parameters of blood serum in female cynomolgus macaques (Macaca fascicularis) in the Adler nursery of the Research Institute of Medical Primatology kept under conditions of free access to the open enclosure. It was found that in the most favorable season for monkeys (from June to September) the serum levels of sodium, phosphorus, creatinine were significantly increased and cholesterol and calcium concentrations and lactate dehydrogenase activity were significantly reduced. There was no seasonal variability in the content of triglycerides, urea, potassium, activity of γ-glutamyltransferase, ALT, and AST.

SARS-like Coronaviruses in Horseshoe Bats ( spp.) in Russia, 2020.

We found and genetically described two novel SARS-like coronaviruses in feces and oral swabs of the greater () and the lesser () horseshoe bats in southern regions of Russia. The viruses, named Khosta-1 and Khosta-2, together with related viruses from Bulgaria and Kenya, form a separate phylogenetic lineage. We found evidence of recombination events in the evolutionary history of Khosta-1, which involved the acquisition of the structural proteins S, E, and M, as well as the nonstructural genes ORF3, ORF6, ORF7a, and ORF7b, from a virus that is related to the Kenyan isolate BtKY72.

[Prevalence of laboratory markers of human respiratory viruses in monkeys of Adler primate center].

Introduction: The relevance of studying the circulation of human respiratory viruses among laboratory primates is associated with the need to test vaccines and antiviral drugs against these infections on monkeys.The aim of this work was to study the prevalence of serological and molecular markers of human respiratory viral infections in laboratory primates born at the Adler Primate Center and in imported monkeys.

Material And Methods: Blood serum samples (n = 1971) and lung autopsy material (n = 26) were obtained from different monkey species.

Study the Differences between the Parameters of Learning and Exploratory Activities in Adult Male Rhesus Monkeys (Macaca mulatta) and Baboon Hamadryas (Papio hamadryas).

We studied exploratory activity and learning ability in sexually mature male rhesus monkeys (Macaca mulatta) and hamadryas baboons (Papio hamadryas). The interspecies differences were analyzed by the following parameters: the level of exploratory activity, diversity of exploratory activity, concentration on the object, learning ability, training levels, and dynamics of learning. The studied group of hamadryas baboons showed higher levels of exploratory activity and learning ability than the group of rhesus monkeys.