Safety and Transcriptome Analysis of Live Attenuated Vaccine Strain S2 on Non-pregnant Monkeys Without Abortive Effect on Pregnant Monkeys.

Shijing Sun, Hui Jiang, Qiaoling Li, Yufu Liu, Qiang Gao, Wei Liu, Yuming Qin, Yu Feng, Xiaowei Peng, Guanlong Xu, Qingchun Shen, Xuezheng Fan, Jiabo Ding, Liangquan Zhu
Author Information
  1. Shijing Sun: National/OIE Reference Laboratory for Animal Brucellosis, China Institute of Veterinary Drug Control (IVDC), Beijing, China.
  2. Hui Jiang: National/OIE Reference Laboratory for Animal Brucellosis, China Institute of Veterinary Drug Control (IVDC), Beijing, China.
  3. Qiaoling Li: National/OIE Reference Laboratory for Animal Brucellosis, China Institute of Veterinary Drug Control (IVDC), Beijing, China.
  4. Yufu Liu: National/OIE Reference Laboratory for Animal Brucellosis, China Institute of Veterinary Drug Control (IVDC), Beijing, China.
  5. Qiang Gao: National/OIE Reference Laboratory for Animal Brucellosis, China Institute of Veterinary Drug Control (IVDC), Beijing, China.
  6. Wei Liu: Academy of Agriculture and Animal Husbandry Sciences, Hohhot, China.
  7. Yuming Qin: National/OIE Reference Laboratory for Animal Brucellosis, China Institute of Veterinary Drug Control (IVDC), Beijing, China.
  8. Yu Feng: National/OIE Reference Laboratory for Animal Brucellosis, China Institute of Veterinary Drug Control (IVDC), Beijing, China.
  9. Xiaowei Peng: National/OIE Reference Laboratory for Animal Brucellosis, China Institute of Veterinary Drug Control (IVDC), Beijing, China.
  10. Guanlong Xu: National/OIE Reference Laboratory for Animal Brucellosis, China Institute of Veterinary Drug Control (IVDC), Beijing, China.
  11. Qingchun Shen: National/OIE Reference Laboratory for Animal Brucellosis, China Institute of Veterinary Drug Control (IVDC), Beijing, China.
  12. Xuezheng Fan: National/OIE Reference Laboratory for Animal Brucellosis, China Institute of Veterinary Drug Control (IVDC), Beijing, China.
  13. Jiabo Ding: National/OIE Reference Laboratory for Animal Brucellosis, China Institute of Veterinary Drug Control (IVDC), Beijing, China.
  14. Liangquan Zhu: National/OIE Reference Laboratory for Animal Brucellosis, China Institute of Veterinary Drug Control (IVDC), Beijing, China.

Abstract

Brucellosis, caused by spp., is an important zoonotic disease leading to enormous economic losses in livestock, posing a great threat to public health worldwide. The live attenuated 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 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 monkeys immunized with the S2 vaccine. Our results suggested that the S2 vaccine was safe for 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.

Keywords

References

  1. J Vet Sci. 2017 Aug 31;18(S1):281-290 [PMID: 28859268]
  2. Comp Immunol Microbiol Infect Dis. 2013 May;36(3):241-8 [PMID: 23044181]
  3. Eur J Pharmacol. 2019 Sep 15;859:172494 [PMID: 31238062]
  4. Lancet Infect Dis. 2006 Feb;6(2):91-9 [PMID: 16439329]
  5. FEMS Microbiol Rev. 2010 May;34(3):379-94 [PMID: 20180858]
  6. PLoS One. 2015 Mar 27;10(3):e0121015 [PMID: 25816068]
  7. Bull World Health Organ. 2003;81(12):867-76 [PMID: 14997239]
  8. Vaccine. 2016 Jan 12;34(3):395-400 [PMID: 26626213]
  9. Biomed Res Int. 2018 Nov 18;2018:1496536 [PMID: 30581844]
  10. BMJ. 2008 Mar 29;336(7646):678-9 [PMID: 18321958]
  11. Emerg Microbes Infect. 2020 Dec;9(1):761-770 [PMID: 32228226]
  12. Comput Struct Biotechnol J. 2020 Nov 21;18:3843-3860 [PMID: 33335683]
  13. Sci Rep. 2020 May 18;10(1):8145 [PMID: 32424199]
  14. Environ Health Prev Med. 2018 Jun 19;23(1):23 [PMID: 29921215]
  15. BMC Genomics. 2016 Sep 20;17(1):741 [PMID: 27645563]
  16. Front Vet Sci. 2021 Jan 07;7:539444 [PMID: 33490123]
  17. BMC Vet Res. 2016 Aug 23;12(1):174 [PMID: 27553600]
  18. Biomed Res Int. 2013;2013:743509 [PMID: 23862154]
  19. Expert Rev Anti Infect Ther. 2011 Jul;9(7):833-45 [PMID: 21810055]
  20. Vet Microbiol. 2002 Dec 20;90(1-4):479-96 [PMID: 12414166]
  21. Vaccine. 1986 Dec;4(4):212-6 [PMID: 3541425]
  22. Front Immunol. 2019 Jul 16;10:1622 [PMID: 31379827]
  23. Vaccine. 2019 Jul 9;37(30):3981-3988 [PMID: 31176541]
  24. Front Vet Sci. 2020 Jan 10;6:459 [PMID: 31998758]
  25. Microb Pathog. 2018 Jun;119:241-247 [PMID: 29626657]
  26. PLoS One. 2019 Jun 14;14(6):e0208292 [PMID: 31199806]
  27. Front Vet Sci. 2020 Sep 02;7:521 [PMID: 32984409]
  28. Infect Dis Poverty. 2020 May 24;9(1):55 [PMID: 32448394]
  29. Infect Ecol Epidemiol. 2018 Jul 24;8(1):1500846 [PMID: 30083304]
  30. Emerg Infect Dis. 2017 Feb;23(2):184-194 [PMID: 28098531]

Word Cloud

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