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ds-7080a, a selective anti-robo4 antibody, shows anti-angiogenic efficacy with distinctly different profiles from anti-vegf agents.neovascular age-related macular degeneration (namd) results from choroidal neovascularization (cnv) and causes severe vision loss. intravitreal anti-vascular endothelial growth factor (vegf) therapies have significantly improved therapeutic outcomes; however, a substantial number of patients experience disease progression. roundabout 4 (robo4) has been reported to be a vascular-specific protein that stabilizes vasculature in ocular pathological angiogenesis. to explore robo4 targeting as a novel ...202032879763
proline protects boar sperm against oxidative stress through proline dehydrogenase-mediated metabolism and the amine structure of pyrrolidine.proline was reported to improve sperm quality in rams, stallions, cynomolgus monkeys, donkeys, and canines during cryopreservation. however, the underlying mechanism remains unclear. the aim of this study was to investigate the effect of proline on boar semen during liquid storage at 17 °c and explore the underlying mechanism. freshly ejaculated boar semen was supplemented with different concentrations of proline (0, 25, 50, 75, 100, 125 mm) and stored at 17 °c for nine days. sperm motility patt ...202032883027
amg 701 induces cytotoxicity of multiple myeloma cells and depletes plasma cells in cynomolgus monkeys.multiple myeloma (mm) is a hematologic malignancy that is characterized by the accumulation of abnormal plasma cells (pcs) in the bone marrow (bm). patient outcome may be improved with bite (bispecific t-cell engager) molecules, which redirect t cells to lyse tumor cells. b-cell maturation antigen (bcma) supports pc survival and is highly expressed on mm cells. a half-life extended anti-bcma bite molecule (amg 701) induced selective cytotoxicity against bcma-expressing mm cells (average half-max ...202032886754
review: other helicobacter species.this review covers the most important, accessible, and relevant literature published between april 2019 and april 2020 in the field of non-helicobacter pylori helicobacter species (nhph). the initial part of the review covers new insights regarding the presence of gastric and enterohepatic nhph in humans and animals, while the subsequent section focuses on the progress in our understanding of animal models, the pathogenicity and omics of these species. over the last year, the clinical relevance ...202032918348
highly improved aqueous lubrication of polymer surface by noncovalently bonding hyaluronic acid-based hydration layer for endotracheal intubation.hydration lubrication is the key responsible for the exceptionally low boundary friction between biosurfaces. however, it is a challenge to settle a hydration layer on a polymer surface via a noncovalent manner. herein, we develop a highly lubricated coating absorbed onto the polymer surface via intermolecular association of hyaluronic acid (ha)-based micelles. a poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) triblock copolymer (pluronic, f127) is recruited to complex with h ...202032920428
assessment of hand motor function in a non-human primate model of ischemic stroke.ischemic stroke results from arterial occlusion and can cause irreversible brain injury. a non-human primate (nhp) model of ischemic stroke was previously developed to investigate its pathophysiology and for efficacy testing of therapeutic candidates; however, fine motor impairment remains to be well-characterized. we evaluated hand motor function in a cynomolgus monkey model of ischemic stroke. endovascular transient middle cerebral artery occlusion (mcao) with an angiographic microcatheter ind ...202032921642
topical nanoparticles interfering with the dna-ll37 complex to alleviate psoriatic inflammation in mice and monkeys.cell-free dna (cfdna) released from damaged or dead cells combines with ll37 and is converted into an immune response activator to exacerbate psoriasis. here, we show that cationic nanoparticles (cnps) efficiently compete for dna from the dna-ll37 immunocomplex and inhibit dna-ll37-induced cell activation. using phenotypical images, psoriasis area and severity index scoring, histology, and immunohistochemical analysis, we demonstrate that topical application of cnps on psoriasiform skin of a mou ...202032923608
experimental techniques for the development of a uterus transplantation model in cynomolgus macaques.uterus transplantation (utx) is now a treatment for women with uterine factor infertility to have a child. however, utx is still largely at the experimental stage, and many medical issues remain unsolved. therefore, adequate studies in large animals including non-human primates are required for validation of these issues. utx research, especially in non-human primates, can provide important information for its full establishment in humans due to the anatomical and physiological similarities betw ...202032924267
argx-117, a therapeutic complement inhibiting antibody targeting c2.activation of the classical and lectin pathway of complement may contribute to tissue damage and organ dysfunction of antibody-mediated diseases and ischemia-reperfusion conditions. complement factors are being considered as targets for therapeutic intervention objective: we here characterize argx-117, a humanized inhibitory monoclonal antibody against complement c2.202032926878
de novo lipogenesis is essential for platelet production in humans.acetyl-coa carboxylase (acc) catalyses the first step of de novo lipogenesis (dnl). pharmacologic inhibition of acc has been of interest for therapeutic intervention in a wide range of diseases. we demonstrate here that acc and dnl are essential for platelet production in humans and monkeys, but in not rodents or dogs. during clinical evaluation of a systemically distributed acc inhibitor, unexpected dose-dependent reductions in platelet count were observed. while platelet count reductions were ...202032929234
an engineered antibody binds a distinct epitope and is a potent inhibitor of murine and human vista.v-domain immunoglobulin (ig) suppressor of t cell activation (vista) is an immune checkpoint that maintains peripheral t cell quiescence and inhibits anti-tumor immune responses. vista functions by dampening the interaction between myeloid cells and t cells, orthogonal to pd-1 and other checkpoints of the tumor-t cell signaling axis. here, we report the use of yeast surface display to engineer an anti-vista antibody that binds with high affinity to mouse, human, and cynomolgus monkey vista. our ...202032938950
terumo spectra optia leukapheresis of cynomolgus macaques for hematopoietic stem cell and t cell collection.macaques are physiologically relevant animal models of human immunology and infectious disease that have provided key insights and advanced clinical treatment in transplantation, vaccinology, and hiv/aids. however, the small size of macaques is a stumbling block for studies requiring large numbers of cells, such as hematopoietic stem cells (hscs) for transplantation, antigen-specific lymphocytes for in-depth immunological analysis, and latently-infected cd4+ t-cells for hiv cure studies. here, w ...202032941672
generation of nonhuman primate model of cone dysfunction through in situ aav-mediated cngb3 ablation.a major challenge to the development of therapies for human retinal degenerative diseases is the lack of an ideal preclinical model because of the physiological differences between humans and most model animals. despite the successful generation of a primate model through germline knockout of a disease-causing gene, the major issues restricting modeling in nonhuman primates (nhps) are their relatively long lifespan, lengthy gestation, and dominant pattern of singleton births. herein, we generate ...202032953936
comparative evaluation of prophylactic siv vaccination modalities administered to the oral cavity.attempts to develop a protective human immunodeficiency virus (hiv) vaccine have had limited success, especially in terms of inducing protective antibodies capable of neutralizing different viral strains. as hiv transmission occurs mainly via mucosal surfaces, hiv replicates significantly in the gastrointestinal tract, and the oral route of vaccination is a very convenient one to implement worldwide, we explored three siv vaccine modalities administered orally and composed of simian immunodefici ...202032962398
trimethylamine n-oxygenation in cynomolgus macaques genotyped for flavin-containing monooxygenase 3 (fmo3).polymorphic human and cynomolgus macaque flavin-containing monooxygenases (fmo) 3 are important oxygenation enzymes for nitrogen-containing drugs. inter-animal variability of fmo3-dependent drug oxygenations in vivo is suspected in cynomolgus macaques because such variability is evident in humans. therefore, this follow-up study was performed to investigate the pharmacokinetics of orally administered deuterium-labeled trimethylamine in three cynomolgus macaques genotyped for fmo3. trimethylamine ...202032967780
preclinical development of mgc018, a duocarmycin-based antibody-drug conjugate targeting b7-h3 for solid cancer.b7-h3, also referred to as cd276, is a member of the b7 family of immune regulatory proteins. b7-h3 is overexpressed on many solid cancers, including prostate cancer, renal cell carcinoma, melanoma, squamous cell carcinoma of the head and neck, non-small cell lung cancer and breast cancer. over-expression of b7-h3 is associated with disease severity, risk of recurrence and reduced survival. in this article, we report the preclinical development of mgc018, an antibody-drug conjugate targeted agai ...202032967924
foreign body reaction, retinal degeneration, and epiretinal membranes associated with intravitreal administration of plga rods.long-acting delivery platforms for intravitreal therapies are an active area of research in ophthalmic drug development. the aim of these platforms is to decrease the burden of intravitreal therapies for patients, by increasing the period between intravitreal injections. this brief communication describes the in-life, histologic and immunohistochemical findings associated with repeat-dose intravitreal administration of poly d, l sustained lactide-co-glycolide polymeric rods, an intravitreal depo ...202032975492
aerosolized ph1n1 influenza infection induces less systemic and local immune activation in the lung than combined intrabronchial, nasal and oral exposure in cynomolgus macaques.non-human primates form an important animal model for the evaluation of immunogenicity and efficacy of novel 'universal' vaccine candidates against influenza virus. however, in most studies a combination of intra-tracheal or intra-bronchial, oral and nasal virus inoculation is used with a standard virus dose of between 1 and 10 million tissue culture infective doses, which differs from typical modes of virus exposure in humans. this paper studies the systemic and local inflammatory and immune ef ...202032975505
oral-fecal mycobiome in wild and captive cynomolgus macaques (macaca fascicularis).cynomolgus macaque (macaca fascicularis) is currently a common animal model for biomedical research. the national primate research center of thailand, chulalongkorn university (nprct-cu) translocated wild-borne macaques to reared colony for research purposes. at present, no studies focus on fungal microbiome (mycobiome) of this macaque. the functional roles of mycobiome and fungal pathogens have not been elucidated. thus, this study aimed to investigate and compare oral and fecal mycobiome betwe ...202032980453
cervico-vaginal inflammatory cytokine and chemokine responses to two different siv immunogens.studies have shown that vaccine vectors and route of immunization can differentially activate different arms of the immune system. however, the effects of different hiv vaccine immunogens on mucosal inflammation have not yet been studied. because mucosal sites are the primary route of hiv infection, we evaluated the cervico-vaginal inflammatory cytokine and chemokine levels of mauritian cynomolgus macaques following immunization and boost using two different siv vaccine immunogens. the pcs vacci ...202032983121
sleep problems in rett syndrome animal models: a systematic review.due to the discovery of rett syndrome (rtt) genetic mutations, animal models have been developed. sleep research in rtt animal models may unravel novel neural mechanisms for this severe neurodevelopmental heritable rare disease. in this systematic literature review we summarize the findings on sleep research of 13 studies in animal models of rtt. we found disturbed efficacy and continuity of sleep in all genetically mutated models of mice, cynomolgus monkeys, and drosophila. models presented hig ...202032985711
predicting the human hepatic clearance of acidic and zwitterionic drugs.prospective predictions of human hepatic clearance for anionic/zwitterionic compounds, which are oftentimes subjected to transporter-mediated uptake, are challenging in drug discovery. we evaluated the utility of preclinical species, rats and cynomolgus monkeys [nonhuman primates (nhps)], to predict the human hepatic clearance using a diverse set of acidic/zwitterionic drugs. preclinical clearance data were generated following intravenous dosing in rats/nhps and compared to the human clearance d ...202032985885
development of rabbit monoclonal antibodies for quantitation of therapeutic human antibodies in preclinical non-human primate studies.during preclinical studies, there is a great need to develop monoclonal antibodies (mabs) that are specific to human immunoglobulin (igg), without binding to monkey igg, to detect therapeutic human mab in non-human primates. we took advantage of the latest rabbit b cell cloning technology to develop six unique rabbit anti-human igg mab clones for this purpose. these clones are capable of binding to both human igg and fab with high affinity without nonspecific binding to cynomolgus monkey igg. th ...202032996830
malaria parasites in macaques in thailand: stump-tailed macaques (macaca arctoides) are new natural hosts for plasmodium knowlesi, plasmodium inui, plasmodium coatneyi and plasmodium fieldi.certain species of macaques are natural hosts of plasmodium knowlesi and plasmodium cynomolgi, which can both cause malaria in humans, and plasmodium inui, which can be experimentally transmitted to humans. a significant number of zoonotic malaria cases have been reported in humans throughout southeast asia, including thailand. there have been only two studies undertaken in thailand to identify malaria parasites in non-human primates in 6 provinces. the objective of this study was to determine t ...202033004070
immunoaffinity enrichment lc-ms/ms quantitation of cdh17 in tissues.aim: there is little information in the literature regarding assays for measuring cdh17 in tissues. numerous studies indicate overexpression of cdh17 in a variety of diseases including hepatocellular carcinoma, colorectal and gastric cancer. here we present an immunoaffinity enrichment lc-ms/ms approach for analysis of cdh17 in human tissues, plasma and serum as well as preclinical models. results: cdh17 levels were measured in colon and ileum tissues from healthy donors and inflamed tissues fro ...202033006478
non-human primate determinants of natural killer cells in tissues at steady-state and during simian immunodeficiency virus infection.natural killer (nk) cells play essential roles in immunity to viruses and tumors. their function is genetically determined but also modulated by environmental factors. the distribution and functional regulation of these cells vary depending on the tissue. nk cell behavior in lymphoid tissues is so far understudied. non-human primate (nhp) models are essential for the development of therapies and vaccines against human diseases, and access to nhp tissues allows insights into spatial regulations o ...202033013901
passive immunisation of convalescent human anti-zika plasma protects against challenge with new world zika virus in cynomolgus macaques.zika virus (zikv) causes neurological complications in susceptible individuals, highlighted in the recent south american epidemic. natural zikv infection elicits host responses capable of preventing subsequent re-infection, raising expectations for effective vaccination. defining protective immune correlates will inform viral intervention strategies, particularly vaccine development. non-human primate (nhp) species are susceptible to zikv and represent models for vaccine development. the protect ...202033014434
age-related decline in expression of molecular chaperones induces endoplasmic reticulum stress and chondrocyte apoptosis in articular cartilage.aging is a major risk factor for the development of osteoarthritis (oa). one hallmark of aging is loss of proteostasis resulting in increased cellular stress and cell death. however, its effect on the development of oa is not clear. here, using knee articular cartilage tissue from young and old cynomolgus monkeys (macaca fascicularis), we demonstrate that with aging there is loss of molecular chaperone expression resulting in endoplasmic reticulum (er) stress and cell death. chondrocytes from ag ...202033014525
site directed mutagenesis at the moco site of the human aldehyde oxidase: interrogating the kinetic differences between human and cynomolgus monkey.the estimation of the drug clearance by aldehyde oxidase (ao) has been complicated because of this enzyme's atypical kinetics and species and substrate specificity. since humans (hao) and cynomolgus monkeys (mao) have a 95.1% sequence identity, cynomolgus monkeys may be the best species for estimating ao clearance in humans. here, o6-benzylguanine (o6bg) and dantrolene were used under anaerobic conditions, as oxidative and reductive substrates of ao respectively, to compare and contrast the kine ...202033020066
preclinical comparison of the blood-brain barrier permeability of osimertinib with other egfr tkis.osimertinib is a potent and selective egfr tyrosine kinase inhibitor (egfr-tki) of both sensitizing and t790m resistance mutations. to treat metastatic brain disease, blood-brain barrier (bbb) permeability is considered desirable for increasing clinical efficacy.202033028591
detection of tuberculosis in cynomolgus macaques (macaca fascicularis) using a supplementary monkey interferon gamma releasing assay (migra).cynomolgus monkeys (macaca fascicularis; mf) are commonly used as nonhuman primate models for pharmaceutical product testing. in their habitat range, monkeys have close contact with humans, allowing the possibility of bidirectional transmission of tuberculosis (tb) between the two species. although the intradermal tuberculin skin test (tst) is used for tb detection in mf, it has limitations. herein, we established the migra, combining human quantiferon-tb gold-plus and monkey ifn-γ elisapro syst ...202033028865
assessment of availability, clinical testing, and us food and drug administration review of biosimilar biologic products.biosimilar biologic products were authorized in 2010, after the us congress established an expedited pathway for approval of clinically similar versions of approved biologic products. unlike for most small-molecule generic drugs, approval requirements for a biosimilar included animal studies and a comparative efficacy clinical trial.202033031559
effects of sevoflurane anaesthesia on radioligand binding to monoamine oxidase-b in vivo.the molecular actions underlying the clinical effects of inhaled anaesthetics such as sevoflurane and isoflurane are not fully understood. unexpected observations in positron emission tomography (pet) studies with [11c]azd9272, a metabotropic glutamate receptor 5 (mglur5) radioligand with possible affinity for monoamine oxidase-b (mao-b), suggest that its binding is sensitive to anaesthesia with sevoflurane. the objective of the present study was to assess the effects of sevoflurane anaesthesia ...202033036760
effective cryopreservation protocol for preservation of male primate (macaca fascicularis) prepubertal fertility.can specimen types (cells versus tissues) and additive cryoprotectant agents contribute to efficient cryopreservation of primate spermatogonial stem cells (ssc)?202033036927
in vitro hepatic uptake in human and monkey hepatocytes in the presence and absence of serum protein and its in vitro to in vivo extrapolation.it is well documented that human hepatic clearance based on in vitro metabolism or transporter assays systematically resulted in underprediction; therefore, large empirical scalars are often needed in either static or physiologically based pharmacokinetic (pbpk) models to accurately predict human pharmacokinetics (pk). in our current investigation, we assessed hepatic uptake (clint,uptake) in hepatocyte suspension in krebs-henseleit buffer (khb) in the presence and absence of serum. the results ...202033037043
blood rna signatures predict recent tuberculosis exposure in mice, macaques and humans.tuberculosis (tb) is the leading cause of death due to a single infectious disease. knowing when a person was infected with mycobacterium tuberculosis (m.tb) is critical as recent infection is the strongest clinical risk factor for progression to tb disease in immunocompetent individuals. however, time since m.tb infection is challenging to determine in routine clinical practice. to define a biomarker for recent tb exposure, we determined whether gene expression patterns in blood rna correlated ...202033037303
use of the illumina epic methylation array for epigenomic research in the crab-eating macaque (macaca fascicularis).commercially available illumina dna methylation arrays (humanmethylation 27k, humanmethylation450, and methylationepic beadchip) can be used for comprehensive dna methylation analyses of not only the human genome but also other mammalian genomes, ranging from those of nonhuman primates to those of rodents. however, practical application of the epic array to the crab-eating macaque has not been reported.202033037870
morphologic characterization of trigeminothalamic terminal arbors arising from the principal nucleus in the macaque.the ventral posterior medial nucleus (vpm) is amandatory relay for orofacial sensory information targeting the primary somatosensory cortex. we characterized the morphology of vpm axons arising in the principal trigeminal sensory nucleus (pv) through injections of biotinylated dextran amine (bda) placed in pv of macaca fascicularis and mulatta monkeys. labeled terminals formed a patchy bilateral distribution. within contralateral vpm, patches were found primarily, but not exclusively, within the ...202033041774
preclinical activity of sar408701: a novel anti-ceacam5-maytansinoid antibody-drug conjugate for the treatment of ceacam5-positive epithelial tumors.carcinoembryonic antigen-related cell adhesion molecule 5 (ceacam5) is a glycoprotein that has limited expression in normal adult tissues, but is overexpressed in carcinomas of the gastrointestinal tract, the genitourinary and respiratory systems, and breast cancer. as such, ceacam5 is an attractive target for antibody-based therapies designed to selectively deliver cytotoxic drugs to certain epithelial tumors. here, we describe preclinical data for a novel antibody-drug conjugate (adc), sar4087 ...202033046521
factors influencing taxonomic unevenness in scientific research: a mixed-methods case study of non-human primate genomic sequence data generation.scholars have noted major disparities in the extent of scientific research conducted among taxonomic groups. such trends may cascade if future scientists gravitate towards study species with more data and resources already available. as new technologies emerge, do research studies employing these technologies continue these disparities? here, using non-human primates as a case study, we identified disparities in massively parallel genomic sequencing data and conducted interviews with scientists ...202033047065
humoral immune responses to burkholderia pseudomallei antigens in captive and wild macaques in the western part of java, indonesia.burkholderia pseudomallei, the gram-negative bacterium which causes melioidosis, is a threat to human and a wide range of animal species. there is an increased concern of melioidosis in indonesian primate facilities, especially following case reports of fatal melioidosis in captive macaques and orangutans. our preliminary serosurveillance of immunoglobulin g (igg) to b. pseudomallei lipopolysaccharide showed that a significant number of captive and wild macaques in the western part of java, indo ...202033050516
interstitial pneumonitis related to trastuzumab deruxtecan, a human epidermal growth factor receptor 2-targeting ab-drug conjugate, in monkeys.trastuzumab deruxtecan (t-dxd: ds-8201a) is an anti-human epidermal growth factor receptor 2 (her2) ab-drug conjugated with deruxtecan (dxd), a derivative of exatecan. the objective of this study was to characterize t-dxd-induced lung toxicity in cynomolgus monkeys. trastuzumab deruxtecan was injected i.v. into monkeys once every 3 weeks for 6 weeks (10, 30, and 78.8 mg/kg) or for 3 months (3, 10, and 30 mg/kg). to evaluate the involvement of dxd alone in t-dxd-induced toxicity, dxd monohydrate ...202033051938
[a comparative study of 3.0t (1)h-mrs for varying degrees of liver fibrosis in cynomolgus monkeys].objective: to investigate the changing rules with (1)h magnetic resonance spectroscopy ((1)h-mrs) in order to provide human research theoretical basis with varying degrees of liver fibrosis in cynomolgus monkeys. methods: liver fibrosis model in twenty-two cynomolgus monkey was successfully established with carbon tetrachloride (ccl(4)). among them, fifteen cynomolgus monkey developed to early-stage liver cirrhosis (s4 stage). a comparative study was conducted in 15 cynomolgus monkeys that had f ...202033053977
cd40l-stimulated b cells for ex vivo expansion of polyspecific nonhuman primate regulatory t cells for translational studies.the therapeutic applications of regulatory t cells (tregs) include treating autoimmune diseases, graft-versus-host disease, and induction of transplantation tolerance. for ex vivo expanded tregs to be used in deceased donor transplantation, they must be able to suppress t-cell responses to a broad range of hla. here, we present a novel approach for the expansion of polyspecific tregs in cynomolgus macaques that was adapted from a good manufacturing practice-compliant protocol.202033058141
comparative pharmacokinetics of puerarin alone and in pueraria mirifica extract in female cynomolgus monkeys.pueraria mirifica is an endemic thai plant that has been used for rejuvenation and in the relief of various aging diseases. puerarin is one of the major isoflavones found in this plant and shows several pharmacological activities in relation to the thai traditional use of p. mirifica. therefore, comparative pharmacokinetics of pure puerarin alone and that in a p. mirifica extract in cynomolgus monkeys were conducted in order to investigate the pharmacokinetic profiles of the 2 preparations. to t ...202033063303
impact of concurrent remifentanil on the sedative effects of remimazolam, midazolam and propofol in cynomolgus monkeys.drug-drug interactions can substantially change pharmacological effects of the individual substances involved. for the use of sedatives or anaesthetics, having knowledge of the extent and characteristics of such interactions is crucial for ensuring the proper protection of patients undergoing any kind of sedation. remimazolam is a new ultra-short acting benzodiazepine that is currently under development for intravenous use in procedural sedation and general anaesthesia. it exhibits a fast onset ...202033065095
decreased immune response in monkeys administered a human t-effector cell agonist (ox40) antibody.the ox40 receptor plays a crucial co-stimulatory role in t effector cell survival, expansion, cytokine production, and cytotoxicity to tumor cells; therefore, ox40 agonists are being evaluated as anti-cancer immunotherapies, especially in combination with checkpoint inhibitors. to support clinical development of bms-986178 (an ox40 agonist antibody), two repeat-dose toxicity studies were conducted in cynomolgus monkeys. in the first study, bms-986178 was administered intravenously (iv) once week ...202033069749
ibi112, a selective anti-il23p19 monoclonal antibody, displays high efficacy in il-23-induced psoriasiform dermatitis.psoriasis is a highly prevalent inflammatory skin disease. plaque psoriasis is the most common type of psoriasis, and the interleukin (il)-23/il-17 axis plays a key role in disease progression. in this article, we describe ibi112, a highly potent anti-il-23 monoclonal antibody under clinical development, which efficiently neutralizes il23p19, a subunit of il-23, to abrogate il-23 binding to its receptor and block downstream signal transducer and activator of transcription 3 (stat3) phosphorylati ...202033069927
comparison of the anatomical morphology of cervical vertebrae between humans and macaques: related to a spinal cord injury model.non-human primates are most suitable for generating cervical experimental models, and it is necessary to study the anatomy of the cervical spine in non-human primates when generating the models. the purpose of this study was to provide the anatomical parameters of the cervical spine and spinal cord in long-tailed macaques (macaca fascicularis) as a basis for cervical spine-related experimental studies. cervical spine specimens from 8 male adult subjects were scanned by micro-computed tomography, ...202033071271
chloroquine potentiates primaquine activity against active and latent hepatic plasmodia ex vivo: potentials and pitfalls.8-aminoquinoline compounds have long been the only therapeutic agents against latent hepatic malaria parasites. these have poor activity against the blood stage plasmodia causing acute malaria and must be used in conjunction with partner blood schizontocidal agents. we examined the impacts of one such agent, chloroquine, upon the activity of primaquine, an 8-aminoquinoline, against hepatic stages of plasmodium cynomolgi, plasmodium yoelii, plasmodium berghei, and plasmodium falciparum within sev ...202033077656
pharmacokinetics of novel fc-engineered monoclonal and multispecific antibodies in cynomolgus monkeys and humanized fcrn transgenic mouse models.monoclonal antibodies (mabs) are among the fastest growing and most effective therapies for myriad diseases. multispecific antibodies are an emerging class of novel therapeutics that can target more than one tumor- or immune-associated modulators per molecule. the combination of different binding affinities and target classes, such as soluble or membrane-bound antigens, within multispecific antibodies confers unique pharmacokinetic (pk) properties. numerous factors affect an antibody's pk, with ...202033079615
dualseqdb: the host-pathogen dual rna sequencing database for infection processes.despite antibiotic resistance being a matter of growing concern worldwide, the bacterial mechanisms of pathogenesis remain underexplored, restraining our ability to develop new antimicrobials. the rise of high-throughput sequencing technology has made available a massive amount of transcriptomic data that could help elucidate the mechanisms underlying bacterial infection. here, we introduce the dualseqdb database, a resource that helps the identification of gene transcriptional changes in both p ...202033084904
novel lcat (lecithin:cholesterol acyltransferase) activator ds-8190a prevents the progression of plaque accumulation in atherosclerosis models.enhancement of lcat (lecithin:cholesterol acyltransferase) activity has possibility to be beneficial for atherosclerosis. to evaluate this concept, we characterized our novel, orally administered, small-molecule lcat activator ds-8190a, which was created from high-throughput screening and subsequent derivatization. we also focused on its mechanism of lcat activation and the therapeutic activity with improvement of hdl (high-density lipoprotein) functionality. approach and results: ds-8190a activ ...202033086872
cd8 t cells show protection against highly pathogenic simian immunodeficiency virus (siv) after vaccination with siv gene-expressing bcg prime and vaccinia virus/sendai virus vector boosts.toward development of a dual vaccine for human immunodeficiency virus (hiv)-1 and tuberculosis infections, we developed a urease-deficient bacillus calmette-guérin (bcg) strain tokyo172 (bcgδurease) to enhance its immunogenicity. bcgδurease expressing simian immunodeficiency virus (siv) gag induced bcg antigen-specific cd4+ and cd8+ t cells more efficiently, and more gag-specific cd8+ t cells. we evaluated its protective efficacy against siv infection in cynomolgus monkeys of asian origin, shown ...202033087465
nonclinical safety, tolerance and pharmacodynamics evaluation for meplazumab treating chloroquine-resistant plasmodium falciparum.meplazumab is an anti-cd147 humanized igg2 antibody. the purpose of this study was to characterize the nonclinical safety, tolerance and efficacy evaluation of meplazumab treating chloroquine resistant plasmodium falciparum. meplazumab was well tolerated in repeat-dose toxicology studies in cynomolgus monkeys. no observed adverse effect level was 12 mg/kg. no difference between genders in the primary toxicokinetic parameters after repeat intravenous injection of meplazumab. no increased levels o ...202033088688
vaccination with intradermal bacillus calmette-guérin provides robust protection against extrapulmonary tuberculosis but not pulmonary infection in cynomolgus macaques.recently, the efficacy of mycobacterium bovis bacillus calmette-guérin (bcg) vaccination is being reassessed in accordance with the achievements of clinical tuberculosis (tb) vaccine research. however, the mechanisms ultimately determining the success or failure of bcg vaccination to prevent pulmonary tb remain poorly understood. in this study, we analyzed the protective effects of intradermal bcg vaccination by using specific pathogen-free cynomolgus macaques of asian origin that were intraderm ...202033097574
pet/ct imaging of 89zr-n-sucdf-pembrolizumab in healthy cynomolgus monkeys.programmed cell death-1 receptor (pd-1) and its ligand (pd-l1) are the targets for immunotherapy in many cancer types. although pd-1 blockade has therapeutic effects, the efficacy differs between patients. factors contributing to this variability are pd-l1 expression levels and immune cells present in tumors. however, it is not well understood how pd-1 expression in the tumor microenvironment impacts immunotherapy response. thus, imaging of pd-1-expressing immune cells is of interest. this study ...202033104972
genome editing of ccr5 by crispr-cas9 in mauritian cynomolgus macaque embryos.the discovery that ccr5 serves as an r5-hiv-1 co-receptor, coupled with findings of protection from hiv infection in individuals lacking ccr5, led to the exploration of novel therapeutic strategies for hiv infection based on genome editing of ccr5. advancing translation of ccr5-mutant-based cellular therapies for hiv requires development of novel physiologically relevant animal models. mauritian cynomolgus macaques (mcms), with high degree of mhc allele sharing, are valuable models for hiv-1 res ...202033116147
central nervous system migration of astaxanthin and adonixanthin following their oral administration in cynomolgus monkeys.astaxanthin, which has been shown to have significant antioxidant activity, is rapidly spreading as a health functioning ingredient in the health food and cosmetics sectors worldwide. it is well known that astaxanthin acts on the brain; however, there is little evidence of brain translocation due to the difficulty in identifying astaxanthin in tissues. therefore, in this study, we investigated the concentrations of astaxanthin and adonixanthin, the latter being a biosynthetic intermediate from β ...202033132354
nvx-cov2373 vaccine protects cynomolgus macaque upper and lower airways against sars-cov-2 challenge.there is an urgent need for a safe and protective vaccine to control the global spread of sars-cov-2 and prevent covid-19. here, we report the immunogenicity and protective efficacy of a sars-cov-2 subunit vaccine (nvx-cov2373) produced from the full-length sars-cov-2 spike (s) glycoprotein stabilized in the prefusion conformation. cynomolgus macaques (macaca fascicularis) immunized with nvx-cov2373 and the saponin-based matrix-m™ adjuvant induced anti-s antibody that was neutralizing and blocke ...202033139139
antibody-mediated activation of the fgfr1/klothoβ complex corrects metabolic dysfunction and alters food preference in obese humans.fibroblast growth factor 21 (fgf21) controls metabolic organ homeostasis and eating/drinking behavior via fgf receptor 1/klothoβ (fgfr1/klb) complexes expressed in adipocytes, pancreatic acinar cells, and the nervous system in mice. chronic administration of recombinant fgf21 or engineered variants improves metabolic health in rodents, nonhuman primates, and humans; however, the rapid turnover of these molecules limits therapeutic utility. here we show that the bispecific anti-fgfr1/klb agonist ...202033139537
a novel dopamine d3r agonist sk609 with norepinephrine transporter inhibition promotes improvement in cognitive task performance in rodent and non-human primate models of parkinson's disease.mild cognitive impairment is present in a number of neurodegenerative disorders including parkinson's disease (pd). mild cognitive impairment in pd (pd-mci) often manifests as deficits in executive functioning, attention, and spatial and working memory. clinical studies have suggested that the development of mild cognitive impairment may be an early symptom of pd and may even precede the onset of motor impairment by several years. dysfunction in several neurotransmitter systems, including dopami ...202033141071
recombinant slamblind measles virus is a promising candidate for nectin-4-positive triple negative breast cancer therapy.one of the most refractory breast cancer types is triple negative (tn) breast cancer, in which cells are resistant to both hormone and herceptin treatments and, thus, often cause recurrence and metastasis. effective treatments are needed to treat tn breast cancer. we previously demonstrated that rmv-slamblind, a recombinant measles virus, showed anti-tumor activity against breast cancer cells. here, we examined whether rmv-slamblind is effective for treating tn breast cancer. nectin-4, a recepto ...202033145396
predicted structural differences of four fertility-related y-chromosome proteins in macaca mulatta, m. fascicularis, and their indochinese hybrids.species in the genus macaca typically live in multimale-multifemale social groups with male macaques exhibiting some of the largest testis:body weight ratios among primates. males are believed to experience intense levels of sperm competition. several spermatogenesis genes are located on the y-chromosome and, interestingly, occasional hybridization between two species has led to the introgression of the rhesus macaque (macaca mulatta) y-chromosome deep into the range of the long-tailed macaque ( ...202033146441
development of highly optimized antibody-drug conjugates (adc) against cd33 and cd123 for acute myeloid leukemia.mortality due to acute myeloid leukemia (aml) remains high, and the management of relapsed or refractory aml continues to be therapeutically challenging. the reapproval of mylotarg, an anti-cd33-calicheamicin antibody-drug conjugate (adc), has provided a proof-of-concept for an adc-based therapeutic for aml. several other adcs have since entered clinical development of aml but have met with limited success. we sought to develop a next-generation adc for aml with a wide therapeutic index that ove ...202033148666
a novel fusion of il-10 engineered to traffic across intestinal epithelium to treat colitis.il-10 is a potent anti-inflammatory cytokine capable of suppressing a number of proinflammatory signals associated with intestinal inflammatory diseases, such as ulcerative colitis and crohn's disease. clinical use of human il-10 (hil-10) has been limited by anemia and thrombocytopenia following systemic injection, side effects that might be eliminated by a gut-restricted distribution. we have identified a transcytosis pathway used by cholix, an exotoxin secreted by nonpandemic forms of the inte ...202033148717
smarcb1 promotes ubiquitination and degradation of nr4a3 via direct interaction driven by ros in vascular endothelial cell injury.nuclear receptor subfamily 4 group a member 3 (nr4a3) protects the vascular endothelial cell (vec) against hypoxia stress, whose expression is primarily reported to be governed at a transcriptional level. however, the regulation of nr4a3 in the protein level is largely unknown. here, we report that nr4a3 protein abundance is decreased immensely in vec injury induced by reoxygenation after oxygen-glucose deprivation (ogd-r), which is significantly blocked by the administration of the antioxidativ ...202033163142
multisite analysis of lesions in the respiratory tract of the rat and nonhuman primate (cynomolgus monkey) exposed to air, vehicle, and inhaled small molecule compounds.this paper presents a review of the nature, range, and incidences of background pathology findings in the respiratory tract of cynomolgus monkeys and rats. data were collected from 81 inhalation studies and 133 non-inhalation studies evaluated at 3 geographically distinct contract research organization facilities. the inhalation studies were comprised of 44 different small molecule pharmaceuticals or chemicals which were also analyzed in order to understand the patterns of induced changes within ...202033167784
transplantation of t-cell receptor α/β-depleted allogeneic bone marrow in nonhuman primates.allogeneic hematopoietic stem cell transplantation (allohsct) is a potentially curative treatment for hematologic cancers and chronic infections such as human immunodeficiency virus (hiv). its success in these settings is attributed to the ability of engrafting immune cells to eliminate cancer cells or deplete the hiv reservoir (graft-versus-host effect [gvhe]). however, allohsct is commonly associated with graft-versus-host diseases (gvhds) causing significant morbidity and mortality, thereby r ...202033176119
plasma and hepatic concentrations of acetaminophen and its primary conjugates after oral administrations determined in experimental animals and humans and extrapolated by pharmacokinetic modeling.plasma concentrations of acetaminophen, its glucuronide and sulfate conjugates, and cysteinyl acetaminophen were experimentally determined after oral administrations of 10 mg/kg in humanized-liver mice, control mice, rats, common marmosets, cynomolgus monkeys, and minipigs; the results were compared with reported human pharmacokinetic data. among the animals tested, only rats predominantly converted acetaminophen to sulfate conjugates, rather than glucuronide conjugates. in contrast, the values ...202033179995
induction of durable antitumor response by a novel oncolytic herpesvirus expressing multiple immunomodulatory transgenes.oncolytic virotherapy is a promising new tool for cancer treatment, but direct lytic destruction of tumor cells is not sufficient and must be accompanied by strong immune activation to elicit anti-tumor immunity. we report here the creation of a novel replication-competent recombinant oncolytic herpes simplex virus type 1 (vg161) that carries genes coding for il-12, il-15, and il-15 receptor alpha subunit, along with a peptide fusion protein capable of disrupting pd-1/pd-l1 interactions. the vg1 ...202033182232
construction of a preliminary three-dimensional structure simian betaretrovirus serotype-2 (srv-2) reverse transcriptase isolated from indonesian cynomolgus monkey.simian betaretrovirus serotype-2 (srv-2) is an important pathogenic agent in asian macaques. it is a potential confounding variable in biomedical research. srv-2 also provides a valuable viral model compared to other retroviruses which can be used for understanding many aspects of retroviral-host interactions and immunosuppression, infection mechanism, retroviral structure, antiretroviral and vaccine development. in this study, we isolated the gene encoding reverse transcriptase enzyme (rt) of s ...202033214855
efficacy of a cap-dependent endonuclease inhibitor and neuraminidase inhibitors against h7n9 highly pathogenic avian influenza virus causing severe viral pneumonia in cynomolgus macaques.h7n9 highly pathogenic avian influenza virus (hpaiv) infection in a human was first reported in 2017. a/duck/japan/aq-he29-22/2017 (h7n9) (dk/he29-22), found in imported duck meat at an airport in japan, possesses a hemagglutinin with a multibasic cleavage site, indicating high pathogenicity in chickens, as in the case of other h7 hpaivs. in the present study, we examined the pathogenicity of dk/he29-22 and the effectiveness of a cap-dependent endonuclease inhibitor (baloxavir) and neuraminidase ...202133257455
a single-dose live-attenuated yf17d-vectored sars-cov-2 vaccine candidate.the expanding pandemic of coronavirus disease 2019 (covid-19) requires the development of safe, efficacious and fast-acting vaccines. several vaccine platforms are being leveraged for a rapid emergency response1. here we describe the development of a candidate vaccine (yf-s0) for severe acute respiratory syndrome coronavirus 2 (sars-cov-2) that uses live-attenuated yellow fever 17d (yf17d) vaccine as a vector to express a noncleavable prefusion form of the sars-cov-2 spike antigen. we assess vac ...202033260195
exposure to zoonotic west nile virus in long-tailed macaques and bats in peninsular malaysia.the role of wildlife such as wild birds, macaques, and bats in the spreading and maintenance of deadly zoonotic pathogens in nature have been well documented in many parts of the world. one such pathogen is the mosquitoes borne virus, namely the west nile virus (wnv). previous research has shown that 1:7 and 1:6 malaysian wild birds are wnv antibody and rna positive, respectively, and bats in north america may not be susceptible to the wnv infection. this study was conducted to determine the sta ...202033321964
nonhuman primate to human immunobridging to infer the protective effect of an ebola virus vaccine candidate.it has been proven challenging to conduct traditional efficacy trials for ebola virus (ebov) vaccines. in the absence of efficacy data, immunobridging is an approach to infer the likelihood of a vaccine protective effect, by translating vaccine immunogenicity in humans to a protective effect, using the relationship between vaccine immunogenicity and the desired outcome in a suitable animal model. we here propose to infer the protective effect of the ad26.zebov, mva-bn-filo vaccine regimen with a ...202033335092
bioinformatic evaluation of the potential animal models for studying sars-cov-2.recently, the severe acute respiratory syndrome coronavirus 2 (sars-cov-2), a novel coronavirus, which results in corona virus disease 2019 (covid-19), has caused over 40 millions of people infected and over 1 million fatalities, challenging the public health. the recognition of its functional receptor, angiotensin converting enzyme 2 (ace2), have facilitated the antivirus drugs testing and vaccines development. due to the natural resistance of mouse model to sars-cov-2, there is an urgent need ...202033364494
systemic viral spreading and defective host responses are associated with fatal lassa fever in macaques.lassa virus (lasv) is endemic in west africa and induces a viral hemorrhagic fever (vhf) with up to 30% lethality among clinical cases. the mechanisms involved in control of lassa fever or, in contrast, the ensuing catastrophic illness and death are poorly understood. we used the cynomolgus monkey model to reproduce the human disease with asymptomatic to mild or fatal disease. after initial replication at the inoculation site, lasv reached the secondary lymphoid organs. lasv did not spread furth ...202133398113
neutralizing antibody-dependent and -independent immune responses against sars-cov-2 in cynomolgus macaques.we examined the pathogenicity of severe acute respiratory syndrome coronavirus-2 (sars-cov-2) in cynomolgus macaques for 28 days to establish an animal model of covid-19 for the development of vaccines and antiviral drugs. cynomolgus macaques infected with sars-cov-2 showed body temperature rises and x-ray radiographic pneumonia without life-threatening clinical signs of disease. a neutralizing antibody against sars-cov-2 and t-lymphocytes producing interferon (ifn)-γ specifically for sars-cov-2 ...202033412411
tetravalent rabies-vectored filovirus and lassa fever vaccine induces long-term immunity in nonhuman primates.the objective of this study is to evaluate the immunogenicity of adjuvanted monovalent rabies virus-based vaccine candidates against ebola virus (filorab1), sudan virus (filorab2), marburg virus (filorab3), lassa virus (lassarab1), and combined trivalent vaccine candidate (filorab1-3) and tetravalent vaccine candidate (filorab1-3 and lassarab) in nonhuman primates.202133421072
west nile virus seroprevalence in an outdoor nonhuman primate breeding colony in south florida.west nile virus (wnv) was first detected in florida in july 2001, with 404 human cases reported to the centers for disease control and prevention as of february 2020. the subtropical climate of florida is ideal for the mosquitoes that transmit wnv. we investigated the wnv seroprevalence in 3 nhp species housed outdoors at the mannheimer foundation in south florida. from january to december 2016, 520 3 to 30 y old nhp were sampled at our 2 closed sites in homestead and labelle: 200 rhesus macaque ...202133441221
development and evaluation of a rapid and cost-efficient ngs-based mhc class i genotyping method for macaques by using a prevalent short-read sequencer.rhesus macaque is one of the most widely used primate model animals for immunological research of infectious diseases including human immunodeficiency virus (hiv) infection. it is well known that major histocompatibility complex (mhc) class i genotypes affect the susceptibility and disease progression to simian immunodeficiency virus (siv) in rhesus macaques, which is resembling to hiv in humans. it is required to convincingly determine the mhc genotypes in the immunological investigations, that ...202133447871
studies on the efficacy, potential cardiotoxicity and monkey pharmacokinetics of glp-26 as a potent hepatitis b virus capsid assembly modulator.while treatment options are available for hepatitis b virus (hbv), there is currently no cure. anti-hbv nucleoside analogs and interferon-alpha 2b rarely clear hbv covalently closed circular dna (cccdna), requiring lifelong treatment. recently, we identified glp-26, a glyoxamide derivative which modulates hbv capsid assembly. the impact of glp-26 on viral replication and integrated dna was assessed in an hbv nude mouse model bearing hbv transfected ad38 xenografts. at day 45 post-infection, glp- ...202133467678
development of a coronavirus disease 2019 nonhuman primate model using airborne exposure.airborne transmission is predicted to be a prevalent route of human exposure with sars-cov-2. aside from african green monkeys, nonhuman primate models that replicate airborne transmission of sars-cov-2 have not been investigated. a comparative evaluation of covid-19 in african green monkeys, rhesus macaques, and cynomolgus macaques following airborne exposure to sars-cov-2 was performed to determine critical disease parameters associated with disease progression, and establish correlations betw ...202133529233
physiological and immunological changes in the brain associated with lethal eastern equine encephalitis virus in macaques.aerosol exposure to eastern equine encephalitis virus (eeev) can trigger a lethal viral encephalitis in cynomolgus macaques which resembles severe human disease. biomarkers indicative of central nervous system (cns) infection by the virus and lethal outcome of disease would be useful in evaluating potential medical countermeasures, especially for therapeutic compounds. to meet requirements of the animal rule, a better understanding of the pathophysiology of eeev-mediated disease in cynomolgus ma ...202133534855
two-component spike nanoparticle vaccine protects macaques from sars-cov-2 infection.the severe acute respiratory syndrome coronavirus 2 (sars-cov-2) pandemic is continuing to disrupt personal lives, global healthcare systems, and economies. hence, there is an urgent need for a vaccine that prevents viral infection, transmission, and disease. here, we present a two-component protein-based nanoparticle vaccine that displays multiple copies of the sars-cov-2 spike protein. immunization studies show that this vaccine induces potent neutralizing antibody responses in mice, rabbits, ...202133577765
cova1-18 neutralizing antibody protects against sars-cov-2 in three preclinical models.one year into the coronavirus disease 2019 (covid-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (sars-cov-2), effective treatments are still needed 1-3 . monoclonal antibodies, given alone or as part of a therapeutic cocktail, have shown promising results in patients, raising the hope that they could play an important role in preventing clinical deterioration in severely ill or in exposed, high risk individuals 4-6 . here, we evaluated the prophylactic and therapeutic ef ...202133619476
comparison of rhesus and cynomolgus macaques as an infection model for covid-19.a novel coronavirus, sars-cov-2, has been identified as the causative agent of the current covid-19 pandemic. animal models, and in particular non-human primates, are essential to understand the pathogenesis of emerging diseases and to assess the safety and efficacy of novel vaccines and therapeutics. here, we show that sars-cov-2 replicates in the upper and lower respiratory tract and causes pulmonary lesions in both rhesus and cynomolgus macaques. immune responses against sars-cov-2 are also s ...202133627662
aerosolized exposure to h5n1 influenza virus causes less severe disease than infection via combined intrabronchial, oral, and nasal inoculation in cynomolgus macaques.infection with highly pathogenic avian h5n1 influenza virus in humans often leads to severe respiratory disease with high mortality. experimental infection in non-human primates can provide additional insight into disease pathogenesis. however, such a model should recapitulate the disease symptoms observed in humans, such as pneumonia and inflammatory cytokine response. while previous studies in macaques have demonstrated the occurrence of typical lesions in the lungs early after infection and a ...202133671829
development and validation of a triplex assay to study an antibody cocktail against ebola virus in cynomolgus serum.background: to support the rapid development of an antibody cocktail against ebola virus and avoid unnecessary exposure to infectious environments, an automatic and fast turnover triplex assay was developed using simoa® (quanterix corporation, ma, usa). materials & methods: a robust triplex assay was developed and validated for simultaneous quantification of the antibody cocktail against ebola virus in cynomolgus serum. results: the assay had a quantitation range of 78.1-5000 ng/ml. the intra- a ...202133792406
transcriptomic analysis reveals host mirnas correlated with immune gene dysregulation during fatal disease progression in the ebola virus cynomolgus macaque disease model.ebola virus is a continuing threat to human populations, causing a virulent hemorrhagic fever disease characterized by dysregulation of both the innate and adaptive host immune responses. severe cases are distinguished by an early, elevated pro-inflammatory response followed by a pronounced lymphopenia with b and t cells unable to mount an effective anti-viral response. the precise mechanisms underlying the dysregulation of the host immune system are poorly understood. in recent years, focus on ...202133806942
the neutralizing antibody, ly-cov555, protects against sars-cov-2 infection in nonhuman primates.severe acute respiratory syndrome coronavirus-2 (sars-cov-2) poses a public health threat for which preventive and therapeutic agents are urgently needed. neutralizing antibodies are a key class of therapeutics that may bridge widespread vaccination campaigns and offer a treatment solution in populations less responsive to vaccination. here, we report that high-throughput microfluidic screening of antigen-specific b cells led to the identification of ly-cov555 (also known as bamlanivimab), a pot ...202133820835
animal models of covid-19. i. comparative virology and disease pathogenesis.the coronavirus disease 2019 (covid-19) pandemic has fueled unprecedented development of animal models to understand disease pathogenesis, test therapeutics, and support vaccine development. models previously developed to study severe acute respiratory syndrome coronavirus (sars-cov) have been rapidly deployed to study sars-cov-2. however, it has become clear that despite the common use of ace2 as a receptor for both viruses, the host range of the 2 viruses does not entirely overlap. distinct ac ...202133836527
therapy for argentine hemorrhagic fever in nonhuman primates with a humanized monoclonal antibody.the covid-19 pandemic has reemphasized the need to identify safe and scalable therapeutics to slow or reverse symptoms of disease caused by newly emerging and reemerging viral pathogens. recent clinical successes of monoclonal antibodies (mabs) in therapy for viral infections demonstrate that mabs offer a solution for these emerging biothreats. we have explored this with respect to junin virus (junv), an arenavirus classified as a category a high-priority agent and the causative agent of argenti ...202133836604
immunogenicity and efficacy of mrna covid-19 vaccine mrt5500 in preclinical animal models.emergency use authorization of covid vaccines has brought hope to mitigate pandemic of coronavirus disease 2019 (covid-19). however, there remains a need for additional effective vaccines to meet the global demand and address the potential new viral variants. mrna technologies offer an expeditious path alternative to traditional vaccine approaches. here we describe the efforts to utilize an mrna platform for rational design and evaluations of mrna vaccine candidates based on the spike (s) glycop ...202133875658
sars-cov-2 in animals: potential for unknown reservoir hosts and public health implications.severe acute respiratory syndrome coronavirus 2 (sars-cov-2, previously 2019-ncov) is suspected of having originated in 2019 in china from a coronavirus infected bat of the genus rhinolophus. following the initial emergence, possibly facilitated by a mammalian bridge host, sars-cov-2 is currently transmitted across the globe via efficient human-to-human transmission. results obtained from experimental studies indicate that animal species such as cats, ferrets, raccoon dogs, cynomolgus macaques, ...202133892621
development and characterization of a highly sensitive nanoluciferase-based immunoprecipitation system for the detection of anti-influenza virus ha antibodies.antibody detection is crucial for monitoring host immune responses to specific pathogen antigens (ags) and evaluating vaccine efficacies. the luciferase immunoprecipitation system (lips) was developed for sensitive detection of ag-specific antibodies in sera from various species. in this study, we describe nanolips, an improved lips assay based on nanoluciferase (nluc), and employ the assay for monitoring antibody responses following influenza virus infection or vaccination. we generated recombi ...202133980684
plant-produced receptor-binding domain of sars-cov-2 elicits potent neutralizing responses in mice and non-human primates.the emergence of coronavirus disease 2019 (covid-19) caused by severe acute respiratory syndrome coronavirus 2 (sars-cov-2) has affected global public health and economy. despite the substantial efforts, only few vaccines are currently approved and some are in the different stages of clinical trials. as the disease rapidly spreads, an affordable and effective vaccine is urgently needed. in this study, we investigated the immunogenicity of plant-produced receptor-binding domain (rbd) of sars-cov- ...202134054909
a single-shot lassa vaccine induces long-term immunity and protects cynomolgus monkeys against heterologous strains.a safe and protective lassa virus vaccine is crucially needed in western africa to stem the recurrent outbreaks of lassa virus infections in nigeria and the emergence of lassa virus in previously unaffected countries, such as benin and togo. major challenges in developing a lassa virus vaccine include the high diversity of circulating strains and their reemergence from 1 year to another. to address each of these challenges, we immunized cynomolgus monkeys with a measles virus vector expressing t ...202134108251
distinct transcriptional responses to fatal ebola virus infection in cynomolgus and rhesus macaques suggest species-specific immune responses.ebola virus (ebov) is a negative single-stranded rna virus within the filoviridae family and the causative agent of ebola virus disease (evd). nonhuman primates (nhps), including cynomolgus and rhesus macaques, are considered the gold standard animal model to interrogate mechanisms of ebov pathogenesis. however, despite significant genetic similarity (>90%), nhp species display different clinical presentation following ebov infection, notably a ∼1-2 days delay in disease progression. consequentl ...202134112056
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