Safety and Transcriptome Analysis of Brucella Live Attenuated Vaccine Strain S2 on Cynomolgus Monkeys
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ABSTRACT:
PROVIDER: PRJNA693863 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR13500345_1.fastq.gz | Fastqsanger.gz | |||
| SRR13500345_2.fastq.gz | Fastqsanger.gz | |||
| SRR13500346_1.fastq.gz | Fastqsanger.gz | |||
| SRR13500346_2.fastq.gz | Fastqsanger.gz | |||
| SRR13500347_1.fastq.gz | Fastqsanger.gz |
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Project description:Brucellosis, caused by Brucella spp, is an important zoonotic disease leading to enormous economic losses in livestock and posing great threat to public health worldwide. The live attenuated Brucella suis (B. suis) strain S2 is a safe and effective vaccine, and it is most widely used in animals in China. However, S2 vaccination in animals may raise debates and concerns in terms of safety to primates, particularly human. In this study, using cynomolgus monkey as an animal model, we evaluated the safety of the S2 vaccine strain on primate, in addition, we performed transcriptome analysis to determine gene expression profiling on cynomolgus monkeys immunized with the S2 vaccine. Our results suggested that the S2 vaccine was safe to cynomolgus monkeys. Transcriptome analysis identified 663 differentially expressed genes (DEGs), of which 348 were significantly up-regulated and 315 were remarkably down-regulated. Gene Ontology (GO) classification and KEGG pathway analysis indicated that these DEGs were involved in various biological processes, including chemokine signaling pathway, actin cytoskeleton regulation, defense response, immune system processing, and type I interferon signaling pathway. The molecular functions of the DEGs mainly comprised of 2'-5'-oligoadenylate synthetase activity, double-stranded RNA binding and actin binding. Moreover, the cellular components of these DEGs included integrin complex, myosin II complex and blood microparticle. Our findings alleviate the concerns in safety of the S2 vaccine on primates and provide genetic basis of mammalian host response and gene regulation after vaccination with the S2 vaccine.
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Project description:Brucellosis, caused by Brucella spp., is an important zoonotic disease leading to enormous economic losses in livestock, posing a great threat to public health worldwide. The live attenuated Brucella suis (B. suis) strain S2, a safe and effective vaccine, is widely used in animals in China. However, S2 vaccination in animals may raise debates and concerns in terms of safety to primates, particularly humans. In this study, we used cynomolgus monkey as an animal model to evaluate the safety of the S2 vaccine strain on primates. In addition, we performed transcriptome analysis to determine gene expression profiling on cynomolgus monkeys immunized with the S2 vaccine. Our results suggested that the S2 vaccine was safe for cynomolgus monkeys. The transcriptome analysis identified 663 differentially expressed genes (DEGs), of which 348 were significantly upregulated and 315 were remarkably downregulated. The Gene Ontology (GO) classification and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that these DEGs were involved in various biological processes (BPs), including the chemokine signaling pathway, actin cytoskeleton regulation, the defense response, immune system processing, and the type-I interferon signaling pathway. The molecular functions of the DEGs were mainly comprised of 2'-5'-oligoadenylate synthetase activity, double-stranded RNA binding, and actin-binding. Moreover, the cellular components of these DEGs included integrin complex, myosin II complex, and blood microparticle. Our findings alleviate the concerns over the safety of the S2 vaccine on primates and provide a genetic basis for the response from a mammalian host following vaccination with the S2 vaccine.
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Project description:Cynomolgus monkeys are well-established translational models for biomedical research and drug testing. To evaluate organ transcriptomes and gene expression variability in Cynomolgus monkeys, we used Customized NimbleGen Microarrays (Design ID: 120419_Cynomolgus_v5_TH_exp_HX12) for genome-wide gene expression profiling on 5 different tissues (heart, kidney, liver, lung, spleen) from 21 Cynomolgus monkeys. Cynomolgus monkey samples were derived from breeding centers located in the Philippines (3 females and 3 males), in Vietnam (2 females and 2 males), in China for animals from Mainland Southeast Asia (3 females), or in Mauritius (4 females and 4 males). Furthermore, genome-wide copy number variation was analyzed in tissue samples from the same animals using a custom NimbleGen 4.2 million probes comparative genomic hybridization (CGH) array to associate CNV genotypes with expression changes of proximal genes.
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Project description:Cynomolgus monkeys are well-established translational models for biomedical research and drug testing. Cynomolgus monkeys are outbred species and exhibit substantial levels of genetic variation which can affect the outcome and interpretation of biomedical studies. Copy number variations (CNVs) are a significant source of genetic diversity and a comprehensive understanding of the genomic impact of CNVs on phenotypic traits is limited. A custom 4.2 million probes comparative genomic hybridization (CGH) array (Design-ID: 120405_Cynomolgus5_CGH_UX1) has been designed on the basis of the Cynomolgus monkey genome (Ebeling et al. (2011) Genome Research; PMID: 21862625) to assess genome-wide copy number variation among Cynomolgus monkeys. Using Cynomolgus monkey specific NimbleGen CGH Microarrays we profiled the genomes of 21 Cynomolgus monkeys. Germline DNA from 21 Cynomolgus monkeys with different origin was tested against a Cynomolgus monkey reference. Cynomolus monkey samples were derived from breeding centers located in the Philippines (3 females and 3 males), in Vietnam (2 males and 2 females), in China for animals from Mainland Southeast Asia (3 females), or in Mauritius (4 females and 4 males). Furthermore genome-wide expression profiles were analyzed in 5 vitally important tissue samples (heart, kidney, liver, lung, spleen) from the same animals using a custom Cynomolgus monkey specific NimbleGen gene expression microarray (design ID: 120419_Cynomolgus_v5_TH_exp_HX12) to associate CNV genotypes with expression changes of proximal genes using a cis expression quantitative trait loci (cis-eQTL) mapping approach. Expression data have been deposited at the NCBI Gene Expression Omnibus (GEO) under accession numbers GSE76560. The array CGH results analyzed in this study are further described in Gschwind A.R. et al. (2016) "Diversity and regulatory impact of copy number variation in the primate Macaca fascicularis". under submission
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Project description:EXPERIMENT: The animal experiments were performed at Shin Nippon Biomedical Laboratories (SNBL), Ltd. (Kagoshima, Japan) in compliance with the Guideline for Animal Experimentation (1987), and in accordance with the Law Concerning the Protection and Control of Animals (1973) and the Standards Relating to the Care and Management of Experimental Animals (1980). This study was approved by the Institutional Animal Care and Use Committee of SNBL and performed in accordance with the ethics criteria contained in the bylaws of the SNBL committee. Each female monkey was paired with a male of proven fertility for one day between day 11 and day 15 of the menstrual cycle. Pregnant females, aged 5-8 years and weighing 2.84-3.76 kg on day 22 of gestation, were allocated randomly to two groups, each with three monkeys, and housed individually. The monkeys were orally dosed with (±)-thalidomide (Lot no. SDH7273/SDJ3347, Wako Pure Chemical Industries, Ltd., Osaka, Japan) at 0 or 20 mg/kg by oral intubation on day 26 of gestation, which was during the critical period for thalidomide-induced teratogenesis [Delahunt and Lassen, 1964; Hendrickx, 1973]. Dosage was adjusted to the body weight on day 22 of gestation and the drug was packed in a gelatin capsule. Control monkeys received the capsule only. ANIMAL MODEL: Macaca fascicularis INTERVAL: NON. PLATFORM: Proprietary Affymetrix NHP GeneChip® Array for Cynomolgus genome derived from Biogen Idec Keywords = Developmental Keywords = Monkeys Keywords = Thalidomide TFetal malformations and early embryonic gene expression response in cynomolgus monkeys maternally exposed to thalidomidechannel oligonucleotide (Affymetrix) platform.
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