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alveolar ridge dimensional changes following ridge preservation procedure: part-2 - cbct 3d analysis in non-human primate model.the aim of this study was to evaluate the efficacy of ridge preservation involving novel devices used for obturation of socket orifice (socket cap; socketkap(™) ) and resorbable cage used for space maintenance in sites with facial wall dehiscence (socket cage; socketkage(™) ).201626498407
alveolar ridge dimensional changes following ridge preservation procedure with novel devices: part 1--cbct linear analysis in non-human primate model.this study sought to investigate dimensional changes to the alveolar bone following extraction and application of novel devices used for obturation of socket orifice (socket cap) and space maintenance in sockets with facial dehiscence (socket cage).201625655480
zika viral dynamics and shedding in rhesus and cynomolgus macaques.infection with zika virus has been associated with serious neurological complications and fetal abnormalities. however, the dynamics of viral infection, replication and shedding are poorly understood. here we show that both rhesus and cynomolgus macaques are highly susceptible to infection by lineages of zika virus that are closely related to, or are currently circulating in, the americas. after subcutaneous viral inoculation, viral rna was detected in blood plasma as early as 1 d after infectio ...201627694931
comparative sacral morphology and the reconstructed tail lengths of five extinct primates: proconsul heseloni, epipliopithecus vindobonensis, archaeolemur edwardsi, megaladapis grandidieri, and palaeopropithecus kelyus.this study evaluated the relationship between the morphology of the sacrum-the sole bony link between the tail or coccyx and the rest of the body-and tail length (including presence/absence) and function using a comparative sample of extant mammals spanning six orders (primates, carnivora, rodentia, diprotodontia, pilosa, scandentia; n = 472). phylogenetically-informed regression methods were used to assess how tail length varied with respect to 11 external and internal (i.e., trabecular) bony s ...201626767965
plague vaccine development: current research and future trends.plague is one of the world's most lethal human diseases caused by yersinia pestis, a gram-negative bacterium. despite overwhelming studies for many years worldwide, there is no safe and effective vaccine against this fatal disease. inhalation of y. pestis bacilli causes pneumonic plague, a fast growing and deadly dangerous disease. f1/lcrv-based vaccines failed to provide adequate protection in african green monkey model in spite of providing protection in mice and cynomolgus macaques. there is ...201628018363
phenotypic features of circulating leukocytes from non-human primates naturally infected with trypanosoma cruzi resemble the major immunological findings observed in human chagas disease.cynomolgus macaques (macaca fascicularis) represent a feasible model for research on chagas disease since natural t. cruzi infection in these primates leads to clinical outcomes similar to those observed in humans. however, it is still unknown whether these clinical similarities are accompanied by equivalent immunological characteristics in the two species. we have performed a detailed immunophenotypic analysis of circulating leukocytes together with systems biology approaches from 15 cynomolgus ...201626808481
a novel simian retrovirus subtype discovered in cynomolgus monkeys (macaca fascicularis).a new simian retrovirus (srv) subtype was discovered in china and the usa from cambodian-origin cynomolgus monkeys. histopathological examination from necropsied animals showed multifocal lymphoplasmacystic and histocytic inflammation. the complete genome sequences demonstrated that the us virus isolates were nearly identical (99.91-99.93 %) and differed only slightly (99.13-99.16 % identical) from the china isolate. phylogenetic analysis showed that the new virus isolates formed a distinct bran ...201627609630
divergent simian arteriviruses cause simian hemorrhagic fever of differing severities in macaques.simian hemorrhagic fever (shf) is a highly lethal disease in captive macaques. three distinct arteriviruses are known etiological agents of past shf epizootics, but only one, simian hemorrhagic fever virus (shfv), has been isolated in cell culture. the natural reservoir(s) of the three viruses have yet to be identified, but african nonhuman primates are suspected. eleven additional divergent simian arteriviruses have been detected recently in diverse and apparently healthy african cercopithecid ...201626908578
simian immunodeficiency virus sivmac239 infection and simian human immunodeficiency virus shiv89.6p infection result in progression to aids in cynomolgus macaques of asian origin.simian immunodeficiency virus (siv) infection models in cynomolgus macaques are important for analysis of the pathogenesis of immunodeficiency virus and for studies on the efficacy of new vaccine candidates. however, very little is known about the pathogenesis of siv or simian human immunodeficiency virus (shiv) in cynomolgus macaques from different asian countries. in the present study, we analysed the infectivity and pathogenicity of ccr5-tropic sivmac and those of dual-tropic shiv89.6p inocul ...201627902330
first complete genome sequence of a simian foamy virus isolate from a cynomolgus macaque.we report here the first complete proviral genome sequence (ddbj/ena/genbank accession no. lc094267) of a simian foamy virus, sfvmfa/cy5061, isolated from a cynomolgus macaque (macaca fascicularis). this proviral genome consists of 12,965 nucleotides and has five open reading frames, gag, pol, env, tas, and bet, as with other foamy viruses.201627908992
a fully human monoclonal antibody targeting pd-l1 with potent anti-tumor activity.programmed cell death ligand-1 (pd-l1) with its receptor pd-1 pathway is overactivated in many tumors. inhibiting the interaction of pd-l1 and pd-1 is an attractive strategy to restore tumor-specific t cell immunity for tumor therapy.201626773772
plasmodium knowlesi: a relevant, versatile experimental malaria model.the primate malaria plasmodium knowlesi has a long-standing history as an experimental malaria model. studies using this model parasite in combination with its various natural and experimental non-human primate hosts have led to important advances in vaccine development and in our understanding of malaria invasion, immunology and parasite-host interactions. the adaptation to long-term in vitro continuous blood stage culture in rhesus monkey, macaca fascicularis and human red blood cells, as well ...201627938428
[the first monkey malaria in turkey: a case of plasmodium knowlesi].plasmodium knowlesi is now added to the known four plasmodium species (p.vivax, p.falciparum, p.malariae, p.ovale) as a cause of malaria in humans because of the recent increasing rate of cases reported from countries of southeastern asia. p.knowlesi which infects macaque monkeys (macaca fascicularis and m.nemestrina) is transmitted to humans especially by anopheles leucosphyrus and an.hackeri mosquitos. first human cases of p.knowlesi malaria have been detected in malaysia which have reached hi ...201627525405
normocyte-binding protein required for human erythrocyte invasion by the zoonotic malaria parasite plasmodium knowlesi.the dominant cause of malaria in malaysia is now plasmodium knowlesi, a zoonotic parasite of cynomolgus macaque monkeys found throughout south east asia. comparative genomic analysis of parasites adapted to in vitro growth in either cynomolgus or human rbcs identified a genomic deletion that includes the gene encoding normocyte-binding protein xa (nbpxa) in parasites growing in cynomolgus rbcs but not in human rbcs. experimental deletion of the nbpxa gene in parasites adapted to growth in human ...201627303038
genetic diversity, natural selection and haplotype grouping of plasmodium knowlesi gamma protein region ii (pkγrii): comparison with the duffy binding protein (pkdbpαrii).plasmodium knowlesi is a simian malaria parasite that has been reported to cause malaria in humans in southeast asia. this parasite invades the erythrocytes of humans and of its natural host, the macaque macaca fascicularis, via interaction between the duffy binding protein region ii (pkdbpαrii) and the duffy antigen receptor on the host erythrocytes. in contrast, the p. knowlesi gamma protein region ii (pkγrii) is not involved in the invasion of p. knowlesi into humans. pkγrii, however, mediate ...201627195821
invasion characteristics of a plasmodium knowlesi line newly isolated from a human.plasmodium knowlesi is extensively used as an important malaria model and is now recognized as an important cause of human malaria in malaysia. the strains of p. knowlesi currently used for research were isolated many decades ago, raising concerns that they might no longer be representative of contemporary parasite populations. we derived a new p. knowlesi line (university malaya line, um01), from a patient admitted in kuala lumpur, malaysia, and compared it with a human-adapted laboratory line ...201627097521
investigation on possible transmission of monkeys' plasmodium to human in a populations living in the equatorial rainforest of the democratic republic of congo.plasmodiums are protozoa that may infect various hosts. only five species are now recognized as naturally parasitizing humans: plasmodium falciparum, plasmodium vivax, plasmodium malariae, plasmodium ovale and plasmodium knowlesi. this fifth species, p. knowlesi, previously identified as naturally parasitizing the monkey macaca fascicularis, has been microscopically confused for a long time with p. malariae or p. falciparum and it was not possible to correctly differentiate them until the advent ...201627141437
a comprehensive microbiological safety approach for agarose encapsulated porcine islets intended for clinical trials.the use of porcine islets to replace insulin-producing islet β-cells, destroyed during the diabetogenic disease process, presents distinct challenges if this option is to become a therapeutic reality for the treatment of type 1 diabetes. these challenges include a thorough evaluation of the microbiological safety of the islets. in this study, we describe a robust porcine islet-screening program that provides a high level of confidence in the microbiological safety of porcine islets suitable for ...201627862363
distribution and prevalence of malaria parasites among long-tailed macaques (macaca fascicularis) in regional populations across southeast asia.plasmodium knowlesi and plasmodium cynomolgi are two malaria parasites naturally transmissible between humans and wild macaque through mosquito vectors, while plasmodium inui can be experimentally transmitted from macaques to humans. one of their major natural hosts, the long-tailed macaque (macaca fascicularis), is host to two other species of plasmodium (plasmodium fieldi and plasmodium coatneyi) and is widely distributed in southeast asia. this study aims to determine the distribution of wild ...201627590474
identification of vaccine-altered circulating b cell phenotypes using mass cytometry and a two-step clustering analysis.broadening our understanding of the abundance and phenotype of b cell subsets that are induced or perturbed by exogenous ags will improve the vaccine evaluation process. mass cytometry (cytof) is being used to increase the number of markers that can be investigated in single cells, and therefore characterize cell phenotype at an unprecedented level. we designed a panel of cytof abs to compare the b cell response in cynomolgus macaques at baseline, and 8 and 28 d after the second homologous immun ...201627183591
mycobacterium tuberculosis infections in cynomolgus monkey transplant recipients and institution of a screening program for the prevention and control of tuberculosis.tuberculosis is a major health concern in not only humans, but also in non-human primates. in this paper, we report recent cases of mycobacterium tuberculosis in cynomolgus monkeys from cambodia used in transplantation research in a korean facility and describe a program instituted to prevent and control subsequent infections.201627998279
early whole blood transcriptional signatures are associated with severity of lung inflammation in cynomolgus macaques with mycobacterium tuberculosis infection.whole blood transcriptional profiling offers great diagnostic and prognostic potential. although studies identified signatures for pulmonary tuberculosis (tb) and transcripts that predict the risk for developing active tb in humans, the early transcriptional changes immediately following mycobacterium tuberculosis infection have not been evaluated. we evaluated the gene expression changes in the cynomolgus macaque model of tb, which recapitulates all clinical aspects of human m. tuberculosis inf ...201627837110
non-human primate models of tuberculosis.among the animal models of tuberculosis (tb), the non-human primates, particularly rhesus macaques (macaca fascicularis) and cynomolgus macaques (macaca mulatta), share the greatest anatomical and physiological similarities with humans. macaques are highly susceptible to mycobacterium tuberculosis infection and manifest the complete spectrum of clinical and pathological manifestations of tb as seen in humans. therefore, the macaque models have been used extensively for investigating the pathogen ...201627726820
diversity of human and macaque airway immune cells at baseline and during tuberculosis infection.immune cells of the distal airways serve as "first responders" of host immunity to the airborne pathogen mycobacterium tuberculosis (mtb). mtb infection of cynomolgus macaques recapitulates the range of human outcomes from clinically silent latent tuberculosis infection (ltbi) to active tuberculosis of various degrees of severity. to further advance the application of this model to human studies, we compared profiles of bronchoalveolar lavage (bal) cells of humans and cynomolgus macaques before ...201627509488
pet ct identifies reactivation risk in cynomolgus macaques with latent m. tuberculosis.mycobacterium tuberculosis infection presents across a spectrum in humans, from latent infection to active tuberculosis. among those with latent tuberculosis, it is now recognized that there is also a spectrum of infection and this likely contributes to the variable risk of reactivation tuberculosis. here, functional imaging with 18f-fluorodeoxygluose positron emission tomography and computed tomography (pet ct) of cynomolgus macaques with latent m. tuberculosis infection was used to characteriz ...201627379816
temporal expression of peripheral blood leukocyte biomarkers in a macaca fascicularis infection model of tuberculosis; comparison with human datasets and analysis with parametric/non-parametric tools for improved diagnostic biomarker identification.a temporal study of gene expression in peripheral blood leukocytes (pbls) from a mycobacterium tuberculosis primary, pulmonary challenge model macaca fascicularis has been conducted. pbl samples were taken prior to challenge and at one, two, four and six weeks post-challenge and labelled, purified rnas hybridised to operon human genome aros v4.0 slides. data analyses revealed a large number of differentially regulated gene entities, which exhibited temporal profiles of expression across the time ...201627228113
effects of b cell depletion on early mycobacterium tuberculosis infection in cynomolgus macaques.although recent studies in mice have shown that components of b cell and humoral immunity can modulate the immune responses against mycobacterium tuberculosis, the roles of these components in human and nonhuman primate infections are unknown. the cynomolgus macaque (macaca fascicularis) model of m. tuberculosis infection closely mirrors the infection outcomes and pathology in human tuberculosis (tb). the present study used rituximab, an anti-cd20 antibody, to deplete b cells in m. tuberculosis- ...201626883591
ultra low dose aerosol challenge with mycobacterium tuberculosis leads to divergent outcomes in rhesus and cynomolgus macaques.well characterised animal models that can accurately predict efficacy are critical to the development of an improved tb vaccine. the use of high dose challenge for measurement of efficacy in non-human primate models brings the risk that vaccines with the potential to be efficacious against natural challenge could appear ineffective and thus disregarded. therefore, there is a need to develop a challenge regimen that is more relevant to natural human infection. this study has established that ultr ...201626786648
respiratory syncytial virus infection in macaques is not suppressed by intranasal sprays of pyrimidine biosynthesis inhibitors.there is imperious need for efficient therapies against ubiquitous and life-threatening respiratory viruses, foremost among them being the human respiratory syncytial virus (hrsv). several research groups who performed functional screens for broad-spectrum antivirals identified compounds targeting the de novo pyrimidine biosynthesis pathway. despite their strong antiviral activity in vitro, whether such antimetabolites are effective in vivo remains highly controversial. here, we evaluated two po ...201626593978
influenza a virus challenge models in cynomolgus macaques using the authentic inhaled aerosol and intra-nasal routes of infection.non-human primates are the animals closest to humans for use in influenza a virus challenge studies, in terms of their phylogenetic relatedness, physiology and immune systems. previous studies have shown that cynomolgus macaques (macaca fascicularis) are permissive for infection with h1n1pdm influenza virus. these studies have typically used combined challenge routes, with the majority being intra-tracheal delivery, and high doses of virus (> 107 infectious units). this paper describes the outco ...201627311020
preclinical pharmacokinetics of mhaa4549a, a human monoclonal antibody to influenza a virus, and the prediction of its efficacious clinical dose for the treatment of patients hospitalized with influenza a.mhaa4549a is a human immunoglobulin g1 (igg1) monoclonal antibody that binds to a highly conserved epitope on the stalk of influenza a hemagglutinin and blocks the hemagglutinin-mediated membrane fusion in the endosome, neutralizing all known human influenza a strains. pharmacokinetics (pk) of mhaa4549a and its related antibodies were determined in dba/2j and balb-c mice at 5 mg/kg and in cynomolgus monkeys at 5 and 100 mg/kg as a single intravenous dose. serum samples were analyzed for antibody ...201627031797
cynomolgus monkeys (macaca fascicularis) experimentally infected with b19v and hepatitis a virus: no evidence of the co-infection as a cause of acute liver failure.this study was conducted to analyse the course and the outcome of the liver disease in the co-infected animals in order to evaluate a possible synergic effect of human parvovirus b19 (b19v) and hepatitis a virus (hav) co-infection. nine adult cynomolgus monkeys were inoculated with serum obtained from a fatal case of b19v infection and/or a faecal suspension of acute hav. the presence of specific antibodies to hav and b19v, liver enzyme levels, viraemia, haematological changes, and necroinflamma ...201627074255
a replication-defective human type 5 adenovirus-based trivalent vaccine confers complete protection against plague in mice and nonhuman primates.currently, no plague vaccine exists in the united states for human use. the capsular antigen (caf1 or f1) and two type 3 secretion system (t3ss) components, the low-calcium-response v antigen (lcrv) and the needle protein yscf, represent protective antigens of yersinia pestis we used a replication-defective human type 5 adenovirus (ad5) vector and constructed recombinant monovalent and trivalent vaccines (rad5-lcrv and rad5-yfv) that expressed either the codon-optimized lcrv or the fusion gene d ...201627170642
generation of transgenic cynomolgus monkeys that express green fluorescent protein throughout the whole body.nonhuman primates are valuable for human disease modelling, because rodents poorly recapitulate some human diseases such as parkinson's disease and alzheimer's disease amongst others. here, we report for the first time, the generation of green fluorescent protein (gfp) transgenic cynomolgus monkeys by lentivirus infection. our data show that the use of a human cytomegalovirus immediate-early enhancer and chicken beta actin promoter (cag) directed the ubiquitous expression of the transgene in cyn ...201627109065
the genomic sequence of lymphocryptovirus from cynomolgus macaque.lymphocryptoviruses such as epstein-barr virus (ebv) cause persistent infections in human and non-human primates, and suppression of the immune system can increase the risk of lymphocryptovirus (lcv)-associated tumor development in both human and non-human primates. to enable lcv infection as a non-clinical model to study effects of therapeutics on ebv immunity, we determined the genomic dna sequence of the lcv from cynomolgus macaque, a species commonly used for non-clinical testing. comparison ...201626590795
samhd1 polymorphisms were significantly correlated with hiv/siv virus load in pbmc from chinese rhesus macaques and cynomolgus macaquesbackground-sterile alpha motif and histidine aspartate domain containing deoxynucleoside triphosphate triphosphohydrolase 1 (samhd1) is one of the novel restriction factors that potently supresses hiv-1 infection in myeloid cells at an early stage in the viral replication cycle. samhd1 activity is blocked by the action of viral accessory protein x (vpx), which targets and recruits samhd1 for proteasomal degradation, in the sivsm/hiv-2 lineage. objective-the impact of samhd1 polymorphisms on vira ...201627758709
attenuated siv causes persisting neuroinflammation in the absence of a chronic viral load and neurotoxic antiretroviral therapy.using simian models, where siv chronic viral loads are naturally controlled in the absence of potentially neurotoxic therapies, we investigated the neuropathological events occurring during times of suppressed viraemia and when these events were initiated.201627258396
improved transduction efficiencies of adeno-associated virus vectors by synthetic cell-permeable peptides.various serotypes of adeno-associated virus (aav) vectors have been used for gene therapy and as research tools. among these serotypes, the aav type 2 vector has been used successfully in human gene therapies. however, the transduction efficiency of aav2 depends on the cell type, and this poses a problem in the efficacy of gene therapy. to improve the transduction efficiency of aav2, we designed a small peptide consisting of epidermal growth factor receptor (egfr) tyrosine kinase inhibitor pepti ...201627614311
phylogeny and history of the lost siv from crab-eating macaques: sivmfa.in the 20th century, thirteen distinct human immunodeficiency viruses emerged following independent cross-species transmission events involving simian immunodeficiency viruses (siv) from african primates. in the late 1900s, pathogenic siv strains also emerged in the united sates among captive asian macaque species following their unintentional infection with siv from african sooty mangabeys (sivsmm). since their discovery in the 1980s, sivs from rhesus macaques (sivmac) and pig-tailed macaques ( ...201627415779
an hiv gp120-cd4 immunogen does not elicit autoimmune antibody responses in cynomolgus macaques.a promising concept for human immunodeficiency virus (hiv) vaccines focuses immunity on the highly conserved transition state structures and epitopes that appear when the hiv glycoprotein gp120 binds to its receptor, cd4. we are developing chimeric antigens (full-length single chain, or flsc) in which gp120 and cd4 sequences are flexibly linked to allow stable intrachain complex formation between the two moieties (a. devico et al., proc natl acad sci u s a 104:17477-17482, 2007, doi:10.1073/pnas ...201627193040
mcpip1/regnase-i inhibits simian immunodeficiency virus and is not counteracted by vpx.we have previously shown that the cellular rnase mcpip1/regnase-1 potently blocks hiv-1 infection in resting cd4+ t-cells. as simian immunodeficiency virus (siv) encodes an accessory protein named vpx, which enhances viral replication in resting cd4+ t-cells by degrading the cellular restriction factor samhd1, we investigated whether mcpip1 restricts siv infection and whether vpx protein antagonizes mcpip1-mediated restriction. in co-transfection studies, human mcpip1 markedly reduced the produc ...201627075251
novel mutant human immunodeficiency virus type 1 strains with high degree of resistance to cynomolgus macaque trimcyp generated by random mutagenesis.old world monkey trim5α strongly suppresses human immunodeficiency virus type 1 (hiv-1) replication. a fusion protein comprising cynomolgus macaque (cm) trim5 and cyclophilin a (cm trimcyp) also potently suppresses hiv-1 replication. however, cm trimcyp fails to suppress a mutant hiv-1 that encodes a mutant capsid protein containing a sivmac239-derived loop between α-helices 4 and 5 (l4/5). there are seven amino acid differences between l4/5 of hiv-1 and sivmac239. here, we investigated the mini ...201626795727
the effects of trim5α polymorphism on hiv-2rod and sivmac239 replication in pbmcs from chinese rhesus macaques and vietnamese-origin cynomolgus macaques.because of the difficulty of obtaining indian-origin rhesus macaques, chinese-origin rhesus macaques (cr) and vietnamese-origin cynomolgus macaques (cm) are now used frequently in hiv/aids research. nonetheless, the effects of trim5α polymorphism on viral replication in both cr and cm are unclear. to address these questions, we recruited 70 unrelated cr and 40 unrelated cm and studied the effect of trim5α polymorphism on hiv-2rod and sivmac239 replication in pbmcs. we found that 3 polymorphisms, ...201626550946
production of infectious dromedary camel hepatitis e virus by a reverse genetic system: potential for zoonotic infection.the pathogenicity, epidemiology and replication mechanism of dromedary camel hepatitis e virus (dchev), a novel hepatitis e virus (hev), has been unclear. here we used a reverse genetic system to produce dchev and examined the possibility of zoonotic infection.201627449916
islet cell transplantation from göttingen minipigs to cynomolgus monkeys: analysis of virus safety.xenotransplantation using pig cells, tissues or organs may be associated with the transmission of porcine zoonotic micro-organisms. hepatitis e virus (hev), porcine cytomegalovirus (pcmv) and porcine endogenous retroviruses (pervs) are potentially zoonotic micro-organisms which do not show clinical symptoms in pigs and which are due to the low expression level difficult to detect. göttingen minipigs (gömp) are often used for biomedical investigations and they are well characterized concerning th ...201627440468
biotransformation of daclatasvir in vitro and in nonclinical species: formation of the main metabolite by pyrrolidine δ-oxidation and rearrangement.daclatasvir is a first-in-class, potent, and selective inhibitor of the hepatitis c virus nonstructural protein 5a replication complex. in support of nonclinical studies during discovery and exploratory development, liquid chromatography-tandem mass spectrometry and nuclear magnetic resonance were used in connection with synthetic and radiosynthetic approaches to investigate the biotransformation of daclatasvir in vitro and in cynomolgus monkeys, dogs, mice, and rats. the results of these studie ...201627029743
the rapid and sustained responses of dendritic cells to influenza virus infection in a non-human primate model.dendritic cells (dcs) are readily infected by influenza viruses and play a crucial role in regulating host innate and adaptive immune responses to viral infection. the aims of this study are to characterize the dynamic changes in the numbers and maturation status of dendritic cells present in the lung and lung-associated lymph nodes (lalns) in the model of a non-human primate (nhp) infected by influenza a virus (iav). cynomolgus macaques were infected with influenza a virus (h3n2) via bronchosco ...201624780366
vaccination against h9n2 avian influenza virus reduces bronchus-associated lymphoid tissue formation in cynomolgus macaques after intranasal virus challenge infection.h9n2 avian influenza virus causes sporadic human infection. since humans do not possess acquired immunity specific to this virus, we examined the pathogenicity of an h9n2 virus isolated from a human and then analyzed protective effects of a vaccine in cynomolgus macaques. after intranasal challenge with a/hong kong/1073/1999 (h9n2) (hk1073) isolated from a human patient, viruses were isolated from nasal and tracheal swabs in unvaccinated macaques with mild fever and body weight loss. a formalin- ...201627910264
marmoset cytochrome p450 4a11, a novel arachidonic acid and lauric acid ω-hydroxylase expressed in liver and kidney tissues.1. a cdna encoding novel cytochrome p450 (p450) 4a enzyme was cloned from marmoset livers by reverse transcription (rt)-polymerase chain reaction (pcr) based on the marmoset genome sequences. the amino acid sequence deduced from p450 4a11 cdna contained consensus sequences of six substrate recognition sites and one heme-binding domain. 2. marmoset p450 4a11, highly identical (85-88%) to cynomolgus monkey and human p450 4a enzymes, was grouped into the same cluster as cynomolgus monkey and human ...201627435360
a new marmoset p450 4f12 enzyme expressed in small intestines and livers efficiently metabolizes antihistaminic drug ebastine.common marmosets (callithrix jacchus) are attracting attention as animal models in preclinical studies for drug development. however, cytochrome p450s (p450s), major drug-metabolizing enzymes, have not been fully identified and characterized in marmosets. in this study, based on the four novel p450 4f genes found on the marmoset genome, we successfully isolated p450 4f2, 4f3b, 4f11, and 4f12 cdnas in marmoset livers. deduced amino acid sequences of the four marmoset p450 4f forms exhibited high ...201627044800
marmoset cytochrome p450 2j2 mainly expressed in small intestines and livers effectively metabolizes human p450 2j2 probe substrates, astemizole and terfenadine.1. common marmoset (callithrix jacchus), a new world monkey, has potential to be a useful animal model in preclinical studies. however, drug metabolizing properties have not been fully understood due to insufficient information on cytochrome p450 (p450), major drug metabolizing enzymes. 2. marmoset p450 2j2 cdna was isolated from marmoset livers. the deduced amino acid sequence showed a high-sequence identity (91%) with cynomolgus monkey and human p450 2j2 enzymes. a phylogenetic tree revealed t ...201626899760
molecular cloning, tissue distribution, and functional characterization of marmoset cytochrome p450 1a1, 1a2, and 1b1.the common marmoset (callithrix jacchus), a new world monkey, has potential to be an animal model for drug metabolism studies. in this study, we identified and characterized cytochrome p450 (p450) 1a1 and 1b1 in addition to the known p450 1a2 in marmosets. marmoset p450 1a1 and 1b1 cdna contained open reading frames encoding 512 and 543 amino acids, respectively, with high sequence identities (90%-93%) to other primate p450 1a1s and 1b1s. a phylogenetic tree based on amino acid sequences showed ...201626502772
cross-species rhesus cytomegalovirus infection of cynomolgus macaques.cytomegaloviruses (cmv) are highly species-specific due to millennia of co-evolution and adaptation to their host, with no successful experimental cross-species infection in primates reported to date. accordingly, full genome phylogenetic analysis of multiple new cmv field isolates derived from two closely related nonhuman primate species, indian-origin rhesus macaques (rm) and mauritian-origin cynomolgus macaques (mcm), revealed distinct and tight lineage clustering according to the species of ...201627829026
a novel strain of cynomolgus macaque cytomegalovirus: implications for host-virus co-evolution.cytomegaloviruses belong to a large, ancient, genus of dna viruses comprised of a wide array of species-specific strains that occur in diverse array of hosts.201627044312
expression of recipient cytomegalovirus in immunosuppressed and xenotransplanted macaca fascicularis may be related to more severe gastrointestinal lesions.xenotransplantation is a potential answer to the current organ shortage, but the risk of infections related to overimmunosuppression is an important parameter that may predict the recipient's long-term survival. cytomegalovirus (cmv) in xenotransplanted and immunosuppressed primates is a well-known cause of disease particularly affecting the gastrointestinal (gi) tract and a zoonotic concern.201625683577
early transcriptional signatures of the immune response to a live attenuated tetravalent dengue vaccine candidate in non-human primates.the development of a vaccine against dengue faces unique challenges, including the complexity of the immune responses to the four antigenically distinct serotypes. genome-wide transcriptional profiling provides insight into the pathways and molecular features that underlie responses to immune system stimulation, and may facilitate predictions of immune protection.201627214236
molecular detection and prevalence of giardia duodenalis and cryptosporidium spp. among long-tailed macaques (macaca fascicularis) in thailand.giardia duodenalis and cryptosporidium spp. are divergent protozoal intestinal parasites that infect human beings and other animals, including non-human primates. although long-tailed macaques (macaca fascicularis) reside in human communities in thailand, the prevalence of giardia spp. and cryptosporidium spp. in these primates has not been previously investigated. the objective of this study was to evaluate long-tailed macaques living near human communities as possible hosts of these intestinal ...201626892616
micrornas regulate host immune response and pathogenesis during influenza infection in rhesus macaques.micrornas (mirnas) are small noncoding rnas that are key regulators of biological processes, including the immune response to viral infections. differential expression levels of cellular mirnas and their predicted targets have been described in the lungs of h1n1-infected balb/c mice, the lungs of h5n1 influenza-infected cynomolgus macaques, and in peripheral blood mononuclear cells (pbmcs) of critically ill patients infected with 2009 pandemic h1n1. however, a longitudinal analysis of changes in ...201627008411
comparison of pathogenicities of h7 avian influenza viruses via intranasal and conjunctival inoculation in cynomolgus macaques.the outbreak of h7n9 low pathogenic avian influenza viruses in china has attracted attention to h7 influenza virus infection in humans. since we have shown that the pathogenicity of h1n1 and h5n1 influenza viruses in macaques was almost the same as that in humans, we compared the pathogenicities of h7 avian influenza viruses in cynomolgus macaques via intranasal and conjunctival inoculation, which mimics natural infection in humans. h7n9 virus, as well as h7n7 highly pathogenic avian influenza v ...201626994587
induction of systemic and mucosal immunity and maintenance of its memory against influenza a virus by nasal vaccination using a new mucosal adjuvant sf-10 derived from pulmonary surfactant in young cynomolgus monkeys.induction of systemic and mucosal immunity and maintenance of its memory was investigated in 12 young male cynomolgus monkeys after intranasal instillation of flu vaccine using a new mucosal adjuvant sf-10 derived from pulmonary surfactant constituents. split-product of influenza virus a/california/7/2009(h1n1)pdm hemagglutinin vaccine (hav) at 15 μg with or without sf-10 and the adjuvant alone were instilled intranasally three times every 2 weeks. sf-10-adjuvanted hav (sf-10-hav) elicited signi ...201626954466
an inactivated rabies virus-based ebola vaccine, filorab1, adjuvanted with glucopyranosyl lipid a in stable emulsion confers complete protection in nonhuman primate challenge models.the 2013-2016 west african ebola virus (ebov) disease outbreak was the largest filovirus outbreak to date. over 28 000 suspected, probable, or confirmed cases have been reported, with a 53% case-fatality rate. the magnitude and international impact of this ebov outbreak has highlighted the urgent need for a safe and efficient ebov vaccine. to this end, we demonstrate the immunogenicity and protective efficacy of filorab1, a recombinant, bivalent, inactivated rabies virus-based ebov vaccine, in r ...201627456709
study of the gastrointestinal parasitic fauna of captive non-human primates (macaca fascicularis).the aim of this study was to examine helminths and protozoans in cynomolgus macaques (macaca fascicularis) imported from registered breeding facilities in china and their relation to health risks for non-human primate handlers in biomedical research centers and in breeding facilities. fresh fecal samples were collected from a total of 443 m. fascicularis and analyzed by copromicroscopical analysis, immunoenzymatic, or molecular assays. as to helminths, whose eggs were shed in 2.03% of the sample ...201626374536
efficacy projection of obiltoxaximab for treatment of inhalational anthrax across a range of disease severity.inhalational anthrax has high mortality even with antibiotic treatment, and antitoxins are now recommended as an adjunct to standard antimicrobial regimens. the efficacy of obiltoxaximab, a monoclonal antibody against anthrax protective antigen (pa), was examined in multiple studies conducted in two animal models of inhalational anthrax. a single intravenous bolus of 1 to 32 mg/kg of body weight obiltoxaximab or placebo was administered to new zealand white rabbits (two studies) and cynomolgus m ...201627431222
obiltoxaximab prevents disseminated bacillus anthracis infection and improves survival during pre- and postexposure prophylaxis in animal models of inhalational anthrax.the centers for disease control and prevention recommend adjunctive antitoxins when systemic anthrax is suspected. obiltoxaximab, a monoclonal antibody against protective antigen (pa), is approved for treatment of inhalational anthrax in combination with antibiotics and for prophylaxis when alternative therapies are not available. the impact of toxin neutralization with obiltoxaximab during pre- and postexposure prophylaxis was explored, and efficacy results that supported the prophylaxis indica ...201627431219
evaluation of early immune response-survival relationship in cynomolgus macaques after anthrax vaccine adsorbed vaccination and bacillus anthracis spore challenge.anthrax vaccine adsorbed (ava, biothrax) is approved by the us food and drug administration for post-exposure prophylaxis (pep) of anthrax in adults. the pep schedule is 3 subcutaneous (sc) doses (0, 14 and 28 days), in conjunction with a 60 day course of antimicrobials. the objectives of this study were to understand the onset of protection from ava pep vaccination and to assess the potential for shortening the duration of antimicrobial treatment (http://www.phe.gov/preparedness/mcm/phemce/docu ...201627155494
a cpg-ficoll nanoparticle adjuvant for anthrax protective antigen enhances immunogenicity and provides single-immunization protection against inhaled anthrax in monkeys.nanoparticulate delivery systems for vaccine adjuvants, designed to enhance targeting of secondary lymphoid organs and activation of apcs, have shown substantial promise for enhanced immunopotentiation. we investigated the adjuvant activity of synthetic oligonucleotides containing cpg-rich motifs linked to the sucrose polymer ficoll, forming soluble 50-nm particles (dv230-ficoll), each containing >100 molecules of the tlr9 ligand, dv230. dv230-ficoll was evaluated as an adjuvant for a candidate ...201626608924
naturally existing oncolytic virus m1 is nonpathogenic for the nonhuman primates after multiple rounds of repeated intravenous injections.cancers figure among the leading causes of morbidity and mortality worldwide. the number of new cases is expected to rise by about 70% over the next 2 decades. development of novel therapeutic agents is urgently needed for clinical cancer therapy. alphavirus m1 is a getah-like virus isolated from china with a genome of positive single-strand rna. we have previously identified that alphavirus m1 is a naturally existing oncolytic virus with significant anticancer activity against different kinds o ...201627296553
a 52-week safety study in cynomolgus macaques for genetically modified rice expressing cry1ab/1ac protein.a 52-week feeding study in cynomolgus macaques was carried out to evaluate the safety of bt rice huahui 1 (hh1), a transgenic rice line expressing cry1ab/1ac protein. monkeys were fed a diet with 20% or 60% hh1 rice, 20% or 60% parental rice (minghui 63, mh63), normal diet, normal diet spiked with purified recombinant cry1ab/1ac fusion protein or bovine serum albumin (bsa) respectively. during the feeding trail, clinical observations were conducted daily, and multiple parameters, including body ...201627338709
predicting the geographical distributions of the macaque hosts and mosquito vectors of plasmodium knowlesi malaria in forested and non-forested areas.plasmodium knowlesi is a zoonotic pathogen, transmitted among macaques and to humans by anopheline mosquitoes. information on p. knowlesi malaria is lacking in most regions so the first step to understand the geographical distribution of disease risk is to define the distributions of the reservoir and vector species.201627125995
the fully synthetic mag-tn3 therapeutic vaccine containing the tetanus toxoid-derived tt830-844 universal epitope provides anti-tumor immunity.malignant transformations are often associated with aberrant glycosylation processes that lead to the expression of new carbohydrate antigens at the surface of tumor cells. of these carbohydrate antigens, the tn antigen is particularly highly expressed in many carcinomas, especially in breast carcinoma. we designed mag-tn3, a fully synthetic vaccine based on three consecutive tn moieties that are o-linked to a cd4+ t cell epitope, to induce anti-tn antibody responses that could be helpful for th ...201626847142
characterization of pharmacologic and pharmacokinetic properties of ccx168, a potent and selective orally administered complement 5a receptor inhibitor, based on preclinical evaluation and randomized phase 1 clinical study.the complement 5a receptor has been an attractive therapeutic target for many autoimmune and inflammatory disorders. however, development of a selective and potent c5ar antagonist has been challenging. here we describe the characterization of ccx168 (avacopan), an orally administered selective and potent c5ar inhibitor. ccx168 blocked the c5a binding, c5a-mediated migration, calcium mobilization, and cd11b upregulation in u937 cells as well as in freshly isolated human neutrophils. ccx168 retain ...201627768695
virus-like particle vaccination protects nonhuman primates from lethal aerosol exposure with marburgvirus (vlp vaccination protects macaques against aerosol challenges).marburg virus (marv) was the first filovirus to be identified following an outbreak of viral hemorrhagic fever disease in marburg, germany in 1967. due to several factors inherent to filoviruses, they are considered a potential bioweapon that could be disseminated via an aerosol route. previous studies demonstrated that marv virus-like particles (vlps) containing the glycoprotein (gp), matrix protein vp40 and nucleoprotein (np) generated using a baculovirus/insect cell expression system could pr ...201627070636
development of a zika virus infection model in cynomolgus macaques.limited availability of indian rhesus macaques (irm) is a bottleneck to study zika virus (zikv) pathogenesis and evaluation of appropriate control measures in non-human primates. to address these issues, we report here the mauritian cynomolgus macaque (mcm) model for zikv infection. in brief, six mcms (seronegative for dengue and zikv) were subdivided into three cohorts with a male and female each and challenged with different doses of asian [prvabc59 (puerto rico) or fss13025 (cambodia)] or afr ...201628066354
[sequencing and phylogenetic tree construction of 18s ribosomal dna from five species of plasmodium from yunnan border between china and myanmar and other areas].to analyze sequence variation and construct phylogenetic tree based on 18s ribosomal dna among five species of plasmodium in yunnan border between china and myanmar and other areas.201630141590
pedicled instep flap and tibial nerve reconstruction in a cynomolgus monkey [macaca fascicularis].a male cynomolgus monkey experienced extensive soft tissue trauma to the right caudal calf area. some weeks after complete healing of the original wounds, the monkey developed a chronic pressure sore on plantar surface of the heel of its right foot. a loss of sensitivity in the sole of the foot was hypothesized. the skin defect was closed by a medial sensate pedicled instep flap followed by counter transplantation of a full thickness graft from the interdigital webspace. the integrity of the tib ...201629955415
[experimental study on lentivirus-mediated multi-genes co-transfection in bone marrow mesenchymal stem cells for treatment of knee osteoarthritis in cynomolgus monkey].to observe the effect of lentivirus-mediated cyclooxygenase 2 (cox-2) and aggrecanase-1 silencing and insulin-like growth factor 1 (igf-1) in bmscs after injecting into the knee joint cavity in cynomolgus monkeys with knee osteoarthritis (oa).201629786374
[investigation of two blood parasitic protozoa infection in farmed macaca fascicularis in guangxi zhuang autonomous region].to investigate the infection situation of blood parasitic protozoa in farmed macaca fascicularis in an animal breeding ground in nanning, guangxi zhuang autonomous region, so as to provide the evidence for the prevention and control of human blood parasitic protozoa.201629469289
contrasted patterns of variation and evolutionary convergence at the antiviral oas1 gene in old world primates.the oligoadenylate synthetase 1 (oas1) enzyme acts as an innate sensor of viral infection and plays a major role in the defense against a wide diversity of viruses. polymorphisms at oas1 have been shown to correlate with differential susceptibility to several infections of great public health significance, including hepatitis c virus, sars coronavirus, and west nile virus. population genetics analyses in hominoids have revealed interesting evolutionary patterns. in central african chimpanzee, oa ...201526156123
the efficacy of inactivated west nile vaccine (wn-vax) in mice and monkeys.west nile virus (wnv) belonging to the genus flavivirus of the family flaviviridae causes nervous system disorder in humans, horses and birds. licensed wnv vaccines are available for use in horses but not for humans. we previously developed an inactivated west nile virus vaccine (wn-vax) using a seed virus from west nile virus (wnv ny99) that was originally isolated in new york city in 1999. in this study, we report the immunogenicity of wn-vax in both mice and non-human primates.201525889682
nonhuman primate models of chikungunya virus infection and disease (chikv nhp model).chikungunya virus (chikv) is a positive-sense rna virus transmitted by aedes mosquitoes. chikv is a reemerging alphavirus that causes acute febrile illness and severe and debilitating polyarthralgia of the peripheral joints. huge epidemics and the rapid spread of chikv seen in india and the indian ocean region established chikv as a global health concern. this concern was further solidified by the recent incursion of the virus into the western hemisphere, a region without pre-existing immunity. ...201526389957
infectious chikungunya virus in the saliva of mice, monkeys and humans.chikungunya virus (chikv) is a reemerging, ordinarily mosquito-transmitted, alphavirus that occasionally produces hemorrhagic manifestations, such as nose bleed and bleeding gums, in human patients. interferon response factor 3 and 7 deficient (irf3/7-/-) mice, which are deficient for interferon α/β responses, reliably develop hemorrhagic manifestations after chikv infection. here we show that infectious virus was present in the oral cavity of chikv infected irf3/7-/- mice, likely due to hemorrh ...201526447467
development of human-like scfv-fc neutralizing botulinum neurotoxin e.botulinum neurotoxins (bonts) are considered to be the most toxic substances known on earth and are responsible for human botulism, a life-threatening disease characterized by flaccid muscle paralysis that occurs naturally by food-poisoning or colonization of the gastrointestinal tract by bont-producing clostridia. bonts have been classified as category a agent by the centers of disease control and prevention (cdc) and are listed among the six agents with the highest risk to be used as bioweapon ...201526440796
adenovirus-vectored vaccine provides postexposure protection to ebola virus-infected nonhuman primates.ebola virus (ebov) causes lethal disease in up to 90% of ebov-infected humans. among vaccines, only the vesicular stomatitis virus platform has been successful in providing postexposure protection in nonhuman primates. here, we show that an adjuvanted human adenovirus serotype 5 (ad5)-vectored vaccine (ad5-zaire ebov glycoprotein) protected 67% (6 of 9) and 25% (1 of 4) of cynomolgus macaques when administered 30 minutes and 24 hours following ebov challenge, respectively. the treatment also pro ...201525957963
structural differences of amyloid-β fibrils revealed by antibodies from phage display.beside neurofibrillary tangles, amyloid plaques are the major histological hallmarks of alzheimer's disease (ad) being composed of aggregated fibrils of β-amyloid (aβ). during the underlying fibrillogenic pathway, starting from a surplus of soluble aβ and leading to mature fibrils, multiple conformations of this peptide appear, including oligomers of various shapes and sizes. to further investigate the fibrillization of β-amyloid and to have tools at hand to monitor the distribution of aggregate ...201526084577
ires-containing veev vaccine protects cynomolgus macaques from ie venezuelan equine encephalitis virus aerosol challenge.venezuelan equine encephalitis virus (veev) is an arbovirus endemic to the americas that is responsible for severe, sometimes fatal, disease in humans and horses. we previously described an ires-based vee vaccine candidate based up the ie serotype that offers complete protection against a lethal subtype ie veev challenge in mice. here we demonstrate the ires-based vaccine's ability to protect against febrile disease in cynomolgus macaques. vaccination was well tolerated and elicited robust neutr ...201526020513
a nonhuman primate scrub typhus model: protective immune responses induced by pkarp47 dna vaccination in cynomolgus macaques.we developed an intradermal (id) challenge cynomolgus macaque (macaca fascicularis) model of scrub typhus, the leading cause of treatable undifferentiated febrile illness in tropical asia, caused by the obligate intracellular bacterium, orientia tsutsugamushi. a well-characterized animal model is required for the development of clinically relevant diagnostic assays and evaluation of therapeutic agents and candidate vaccines. we investigated scrub typhus disease pathophysiology and evaluated two ...201525601925
comparison of experimental respiratory tularemia in three nonhuman primate species.tularemia is a zoonotic disease caused by francisella tularensis, which is transmitted to humans most commonly by contact with infected animals, tick bites, or inhalation of aerosolized bacteria. f. tularensis is highly infectious via the aerosol route; inhalation of as few as 10-50 organisms can cause pneumonic tularemia. left untreated, the pneumonic form has more than >30% case-fatality rate but with early antibiotic intervention can be reduced to 3%. this study compared tularemia disease pro ...201525766142
distribution of sulphated macromolecules in the salivary secretions of macaca irus. 20154531848
development of real-time pcr assays for the detection of moraxella macacae associated with bloody nose syndrome in rhesus (macaca mulatta) and cynomolgus (macaca fascicularis) macaques.moraxella macacae is a recently described bacterial pathogen that causes epistaxis or so-called bloody nose syndrome in captive macaques. the aim of this study was to develop specific molecular diagnostic assays for m. macacae and to determine their performance characteristics.201526365904
non-clinical safety evaluation of repeated intramuscular administration of the as15 immunostimulant combined with various antigens in rabbits and cynomolgus monkeys.combination of tumor antigens with immunostimulants is a promising approach in cancer immunotherapy. we assessed animal model toxicity of as15 combined with various tumor antigens: wt1 (rabbits), or p501, dher2 and recprame (cynomolgus monkeys), administered in seven or 20 dose regimens versus a saline control. clinical and ophthalmological examinations, followed by extensive post-mortem pathological examinations, were performed on all animals. blood hematology and biochemistry parameters were a ...201526032931
b-1 lymphocytes in mice and nonhuman primates.b-1 cells comprise subpopulations of b lymphocytes in mice that display developmental, phenotypic, and functional characteristics that are distinct from those of conventional b cell populations (b-2 cells). despite the known importance of murine b-1a (cd5(+) ) and b-1b (cd5(-) ) cells in the production of natural antibodies and rapid antigen-specific humoral responses to infection, evidence for b-1 cells in primates, including humans, is very limited. identifying these cells in humans proves cha ...201525930711
metabolism of the vitamin-a-transporting protein complex: turnover of retinol-binding protein, prealbumin and vitamin a in a primate (macaca irus). 20154629506
the preclinical pharmacology of the high affinity anti-il-6r nanobody® alx-0061 supports its clinical development in rheumatoid arthritis.the pleiotropic cytokine interleukin-6 (il-6) plays an important role in the pathogenesis of different diseases, including rheumatoid arthritis (ra). alx-0061 is a bispecific nanobody® with a high affinity and potency for il-6 receptor (il-6r), combined with an extended half-life by targeting human serum albumin. we describe here the relevant aspects of its in vitro and in vivo pharmacology.201525994180
the peptide vaccine combined with prior immunization of a conventional diphtheria-tetanus toxoid vaccine induced amyloid β binding antibodies on cynomolgus monkeys and guinea pigs.the reduction of brain amyloid beta (aβ) peptides by anti-aβ antibodies is one of the possible therapies for alzheimer's disease. we previously reported that the aβ peptide vaccine including the t-cell epitope of diphtheria-tetanus combined toxoid (dt) induced anti-aβ antibodies, and the prior immunization with conventional dt vaccine enhanced the immunogenicity of the peptide. cynomolgus monkeys were given the peptide vaccine subcutaneously in combination with the prior dt vaccination. vaccinat ...201526539559
genetic diversity and natural selection of the plasmodium knowlesi circumsporozoite protein nonrepeat regions.plasmodium knowlesi is a simian malaria parasite that has been identified to cause malaria in humans. to date, several thousand cases of human knowlesi malaria have been reported around southeast asia. thus far, there is no detailed study on genetic diversity and natural selection of p. knowlesi circumsporozoite protein (csp), a prominent surface antigen on the sporozoite of the parasite. in the present study, the genetic diversity and natural selection acting on the nonrepeat regions of the gen ...201526379157
admixture in humans of two divergent plasmodium knowlesi populations associated with different macaque host species.human malaria parasite species were originally acquired from other primate hosts and subsequently became endemic, then spread throughout large parts of the world. a major zoonosis is now occurring with plasmodium knowlesi from macaques in southeast asia, with a recent acceleration in numbers of reported cases particularly in malaysia. to investigate the parasite population genetics, we developed sensitive and species-specific microsatellite genotyping protocols and applied these to analysis of s ...201526020959
piwi proteins and pirnas in mammalian oocytes and early embryos: from sample to sequence.the role of the piwi/pirna pathway during mammalian oogenesis has remained enigmatic thus far, especially since experiments with piwi knockout mice did not reveal any phenotypic defects in female individuals. this is in striking contrast with results obtained from other species including flies and zebrafish. in mouse oocytes, however, only low levels of pirnas are found and they are not required for their function. we recently demonstrated dynamic expression of piwil1, piwil2, and piwil3 during ...201526484274
serum biomarkers of burkholderia mallei infection elucidated by proteomic imaging of skin and lung abscesses.the bacterium burkholderia mallei is the etiological agent of glanders, a highly contagious, often fatal zoonotic infectious disease that is also a biodefense concern. clinical laboratory assays that analyze blood or other biological fluids are the highest priority because these specimens can be collected with minimal risk to the patient. however, progress in developing sensitive assays for monitoring b. mallei infection is hampered by a shortage of useful biomarkers.201526034464
characterization of cellular immune response and innate immune signaling in human and nonhuman primate primary mononuclear cells exposed to burkholderia mallei.burkholderia pseudomallei infection causes melioidosis and is often characterized by severe sepsis. although rare in humans, burkholderia mallei has caused infections in laboratory workers, and the early innate cellular response to b. mallei in human and nonhuman primates has not been characterized. in this study, we examined the primary cellular immune response to b. mallei in pbmc cultures of non-human primates (nhps), chlorocebus aethiops (african green monkeys), macaca fascicularis (cynomolg ...201525450887
potent neutralizing anti-cd1d antibody reduces lung cytokine release in primate asthma model.cd1d is a receptor on antigen-presenting cells involved in triggering cell populations, particularly natural killer t (nkt) cells, to release high levels of cytokines. nkt cells are implicated in asthma pathology and blockade of the cd1d/nkt cell pathway may have therapeutic potential. we developed a potent anti-human cd1d antibody (nib.2) that possesses high affinity for human and cynomolgus macaque cd1d (kd ∼100 pm) and strong neutralizing activity in human primary cell-based assays (ic50 typi ...201525751125
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