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OIE Collaborating Centres Reports Activities Activities in 2016 This report has been submitted : 2017-01-09 08:23:41 Title of collaborating centre: Zoonoses of Asia- Address of Collaborating Centre: Chinese Academy of Agricultural Sciences No 678 Haping Street Nangang District Harbin, Heilongjiang, 150067 CHINA (PEOPLES REP. OF) Tel.: +86-451-5105-1671 Fax: +86-451-51997166 E-mail address: Zj@hvri.ac.cn Website: www.hvri.ac.cn Name of Director of Institute (Responsible Official): Bu Zhigao Name (including Title and Position) of Head of the Collaborating Centre (formally OIE Contact Point): Bu Zhigao Name of writer: Zhang Jing OIE Collaborating Centres Reports Activities, 2016 1

Zoonoses of Asia- - Harbin Veterinary Research Institute ToR: To provide services to the OIE, in particular within the region, in the designated specialty, in support of the implementation of OIE policies and, where required, seek for collaboration with OIE Reference Laboratories ToR: To identify and maintain existing expertise, in particular within its region 1. Activities as a centre of research, expertise, standardisation and dissemination of techniques within the remit of the mandate given by the OIE Disease control analysis the HA sequence of H5 avian influenza viruses of Indonesia In collaboration with the company of Indonesia, PT Biotis Prima Agrisindo, we analysed the HA sequence of H5 avian influenza viruses isolated in Indonesia and used this information for avian influenza vaccine development to control the highly pathogenic avian influenza in Indonesia. Basic research on Bovine Tuberculosis Characterization of special enzymes which might contribute to pathogen invasion, including secretory nuclease, sphingomyelinase and hyaluronidase, was performed. The functions ofpe/ppe family genes frommtb were explored. The effects of different cofactors (L-His, L-Lys, VB1, Vc) on the transcriptional regulation of Mycobacteriumbovis BCG were systematically studied. Basic research on Toxoplasma gondii Characterization of aspartyl aminopeptidases as drug targets against Toxoplasma gondii were conducted in this year. The interaction between RON proteins of T. gondiiwas analyzed to investigate the molecular mechanisms of MJ complex in invasion. Epidemiology, surveillance, risk assessment, modelling Porcine streptococcal infection Sixteen Streptococcus suis strains were isolated from lung tissues of seven died pigs from a pig farm in Zhengzhou, Henan province, China. Serotypes 4, 5, 11 and 16 were found in these 16 strains. Bovine Tuberculosis In 2016, 1416 and 2174 Bovine samples of sera and full blood samples were collected for Mycobacteriumbovisand Mycobacterium paratuberculosisantibody test and IFN-γ release trail from northeast China and partial regions of northwest China. Training, capacity building Hands-on Training Five researchers, Professor Zhanbolat and 4 colleagues from S.Seifullin Kazakh Agro Technical University were invited to attend a hands-on training at Harbin. Zoonoses 2 OIE Collaborating Centres Reports Activities, 2016

Zoonoses of Asia- - Harbin Veterinary Research Institute Control of Brucellosis About one thousand of celisa kits for detection of the brucella antibody were produced and input in the field in China The recovery of brucellosis vaccine Porcine streptococcal infection Three brucellosis vaccine strains including S19,M5-90 and S2 were recovered successfully and produced in 2016. Functions of two virulence factors of Streptococcus suis, sortase A and Gbp, were studied. Porcine streptococcal infection Functions of sortase were elucidated on both biochemical and structural sides. A strong natural product inhibitor for sortase A has been discovered. Gbp was newly found to bind an important protein of host. Diagnosis, biotechnology and laboratory Dignosis of brucellosis About 500 field sera from sheep and goats in China were collected and tested by RBT and celisa Diagnosis of Bovine Tuberculosis Indirect ELISA for detection of Mycobacteriumbovis specific antibody and PCR amplification methodfor Mb specific gene has been well established.the development of detection method for indirect ELISA for detection of Mycobacteriumparatuberculosis specific antibody is close to success. Veterinary medicinal products Production of the reagents for AI Production of the vaccines for AI A series of reagents are produced with a total of 101,104 ml in 2016, including AI type antigens(h5,h7,h9) Reassortant Avian Influenza Virus H5/H9 Subtype Vaccine are produced about 5.1 billion ml Avian influenza vaccine Total about 5.1 billions ml avian influenza vaccine, 100 thousand ml AI type regents for HI test, and 415 RT-PCR kits have been supplied to China, Egypt, Vietnam and Hong Kong Vaccines the development of new inactivated vaccine (H5N1, Egy/PR8-4) To make the vaccine strain well match the antigenicity of the circulating H5 avian influenza viruses in Egypt, we developed a new inactivated vaccine (H5N1, Egy/PR8-4) based on the H5 virus isolated in Egypt and found this updated vaccine could provide complete protection against the current H5N1 viruses in Egypt. oral immunization of rabies vectored EBOV and MARV vaccine in mouse NDV vectored vesicular stomatitis virus provide full protection in mice we generated a rabies virus vectored EBOV vaccine, orally immunized with the vaccine could induce EBOV neutralizing antibodies in mice and dogs we generated a NDV vectored VSV vaccine could induce high neutralizing titer and fully protection for mice OIE Collaborating Centres Reports Activities, 2016 3

Zoonoses of Asia- - Harbin Veterinary Research Institute MERS vaccine a VSV vectored MERS vaccine had been tested in monkeys, results showed the single dose vaccine could induce neutralizing antibodies and T cell responses in monkeys; a NDV based MERS vaccine results could induce high level MERS neutralizing antibodies in camels after two dose immunization. Plenary immune-protection assay is ongoing. ToR : To propose or develop methods and procedures that facilitate harmonisation of international standards and guidelines applicable to the designated specialty 2. Proposal or development of any procedure that will facilitate harmonisation of international regulations applicable to the surveillance and control of animal diseases, food safety or animal welfare Proposal title /Content Applicable area AI DNA vaccine Our DNA vaccine for H5 avian influenza virus has passed the final step evaluation and is ready to be manufactured and applied in poultry. Surveillance and control of animal diseases Food safety Animal welfare The large scale clinical trial of the duck enteritis virus We are performing the large scale clinical trial of the duck enteritis virus vectored H5 vaccine; over 40,000 poultry have been vaccinated in poultry farms in China. Surveillance and control of animal diseases Food safety Animal welfare the vaccine of brucellosis A marker vaccine (DIVA) of B.melitens was licensed to carried out clinical test by Ministry of Agriculture, P.R. China. Surveillance and control of animal diseases Food safety Animal welfare Rabies vaccine Oral vaccine and vector live vaccine of Rabies regulations on production and examination of rabies vaccine have been worked out this year. Surveillance and control of animal diseases Food safety Animal welfare ToR: To establish and maintain a network with other OIE Collaborating Centres designated for the same specialty, and should the need arise, with Collaborating Centres in other disciplines ToR: To carry out and/or coordinate scientific and technical studies in collaboration with other centres, laboratories or organisations 3. Did your Collaborating Centre maintain a network with other OIE Collaborating Centres (CC), Reference Laboratories (RL), or organisations designated for the same specialty, to coordinate scientific and technical studies? 4 OIE Collaborating Centres Reports Activities, 2016

Zoonoses of Asia- - Harbin Veterinary Research Institute Name of OIE CC/RL/other organisation(s) Location Region of networking Centre Purpose ELISA and Molecular Techniques in Animal Disease Diagnosis, FAO/IAEA Animal Production and Health Laboratory. Vienna To apply for the FP7 project:linking Epidemiology and Laboratory Research on Transboundary Animal Diseases and zoonoses in China and EU the OIE cc- of Biotechnology-based Diagnosis of Infectious Diseases in Veterinary Medicine National Veterinary Institute, Sweden. Sweden To apply for the FP7 project:linking Epidemiology and Laboratory Research on Transboundary Animal Diseases and zoonoses in China and EU. Food and Agriculture Organization of the United Nations (FAO) Italy conducting genetic sequence analysis of the swine influenza virus and field sampling and laboratory teseting to characterize viruses in the livestock sector Surveillance and Control of animal protozoan Diseases Japan acedemic exchange of protozoan diseases 4. Did your Collaborating Centre maintain a network with other OIE Collaborating Centres, Reference laboratories, or organisations in other disciplines, to coordinate scientific and technical studies? Name of OIE CC/RL/other organisation(s) Location Region of networking Centre Purpose Bill&Melinda Gates Foundation, Afican Union-Pan n Veterinary Vaccine Centre USA in n countries. PANVAC, French Agricultural Research Frence in n countries. OIE Collaborating Centres Reports Activities, 2016 5

Zoonoses of Asia- - Harbin Veterinary Research Institute Centre for International Development (CIRAD), Frech in n countries. International Livestock Research Kenya in n countries. Live Veterinary Medicines(GALVmed) United Kingdom in n countries. ToR: To place expert consultants at the disposal of the OIE. 5. Did your Collaborating Centre place expert consultants at the disposal of the OIE? Name of expert Kind of consultancy Subject Dr Chen Hualan Conselor To update the the Terrestrial Manual Dr. Xianying Zeng Conselor Dr. Xianying Zeng in our laboratory went to Indonesia to provide technical assistance for avian influenza vaccine development from July 22-25th, 2016. Dr. Huanliang Yang Conselor Dr. Huanliang Yang participated the FAO conference Stakeholder Consultative Workshop to Strengthen the Influenza Surveillance Networks in Guangdong Province, China, 8-9 September 2016, and provided the update on epidemiology, biological characteristics, genetic basis, pathogenicity, and vaccine update of animal influenza in China. Dr. Li Yanbing Conselor Yanbing Li presented Epidemiology and control strategy for HPAI in China, on May 11th, in Seoul Korea; The diagnosis for HPAI in China on May 12th, in Anyang, Korea, respectively, at KIST-Konkuk ORP workshop for on-site diagnosis and HTS system for Avian Influenza, 6 OIE Collaborating Centres Reports Activities, 2016

Zoonoses of Asia- - Harbin Veterinary Research Institute ToR: To provide, within the designated specialty, scientific and technical training to personnel from OIE Member Countries 6. Did your Collaborating Centre provide scientific and technical training, within the remit of the mandate given by the OIE, to personnel from OIE Member Countries? a) Technical visits: 53 b) Seminars: 0 c) Hands-on training courses: 1 d) Internships (>1 month): 0 Type of technical training provided (a, b, c or d) Content Country of origin of the expert(s) provided with training No. participants from the corresponding country c Five researchers, Professor Zhanbolat and 4 colleagues from S.Seifullin Kazakh Agro Technical University were invited to attend a hands-on training at Harbin Kazakhstan 5 a academic exchange United Kindom 4 a academic exchange USA 10 a academic exchange Belgium 11 a academic exchange Germany 1 a academic exchange Japan 6 a academic exchange Spain 2 a Joint research program Russia 4 ToR: To organise and participate in scientific meetings and other activities on behalf of the OIE 7. Did your Collaborating Centre organise or participate in the organisation of scientific meetings on behalf of the OIE? National/International Title of event Co-organiser Date (mm/yy) Location No. Participants OIE Collaborating Centres Reports Activities, 2016 7

Zoonoses of Asia- - Harbin Veterinary Research Institute China The Final Event of LinkTADs in China took place on 19 October 2016 as a special session within the Framework of the 12th Symposium of Chinese Association of Animal Science and Veterinary Medicine, which was organized in Kunming, China. FAO 10/2016 Kunming 60 ToR: To collect, process, analyse, publish and disseminate data and information relevant to the designated specialty 8. Publication and dissemination of any information within the remit of the mandate given by the OIE that may be useful to Member Countries of the OIE a) Articles published in peer-reviewed journals: 15 1) W. Wang, X. Sun, Y. Li, J. Su, Z. Ling, T. Zhang, F. Wang, H. Zhang, H. Chen*, J. Ding*, and B. Sun* (2016). Human antibody 3E1 targets the HA stem region of H1N1 and H5N6 influenza A viruses. Nature Communications, accepted. 2) P. Zhu, L. Liang, X. Shao, W. Luo, S. Jiang, Q. Zhao, N. Sun, Y. Zhao, J. Li, J. Wang, Y. Zhou, J. Zhang, G. Wang, L. Jiang, H. Chen*, C. Li*(2016). Host cellular protein TRAPPC6A interacts with influenza A virus M2 protein and regulates viral propagation by modulating M2 trafficking. Journal of Virology, online Oct 19. 3) L. Liu, X. Zeng, P. Chen, G. Deng, Y. Li, J. Shi, C. Gu, H. Kong, Y. Suzuki, Y. Jiang, G. Tian, H. Chen*(2016). Characterization of clade 7.2 H5 avian influenza viruses that continue to circulate in chickens in China. Journal of Virology, 90 (21): 9797-9805. 4) P. Cui, G. Deng*, J. Shi, H. Kong, L. Liu, Y. Guan, Y. Suzuki, H. Chen*(2016). New influenza A(H7N7) viruses detected in live poultry markets in China. Virology, 499: 165-169 5) X. Li, J. Yang, B. Liu, Y. Jia, J. Guo, X. Gao, S. Weng, M. Yang, L. Wang, L. Wang, J. Cui*, H. Chen*, Q. Zhu*(2016). Co-circulation of H5N6, H3N2, H3N8, and Emergence of Novel Reassortant H3N6 in a Local Community in Hunan Province in China. Scientific Reports, 6: 25549. 6) J. Sui, D. Yang, C. Qiao*, H. Xu, B. Xu, Y. Wu, H. Yang, Y. Chen, H. Chen*(2016). Protective efficacy of an inactivated Eurasian avian-like H1N1 swine influenza vaccine against homologous H1N1 and heterologous H1N1 and H1N2 viruses in mice. Vaccine, 34(33):3757-63 7) X. Zeng, P. Chen, L. Liu, G. Deng, Y. Li, J. Shi, H. Kong, H. Feng, J. Bai, X. Li, G. Tian*, H. Chen*(2016). Protective efficacy of an H5N1 inactivated vaccine against challenge with lethal H5N1, H5N2, H5N6, and H5N8 influenza viruses in chickens. Avian diseases, 60: 253-5. 8) X. Zeng, G. Deng, L. Liu, Y. Li, J. Shi, P. Chen, H. Feng, J. Liu, X. Guo, S. Mao, F. Yang, Z. Chen, G. Tian*, H. Chen*(2016). Protective efficacy of the inactivated H5N1 Influenza vaccine Re-6 against different clades of H5N1 viruses isolated in China and the Democratic People's Republic of Korea. Avian diseases, 60: 238-40. 9) H. Yang, Y. Chen, C. Qiao, X. He, H. Zhou, Y. Sun, H. Yin, S. Meng, L. Liu, Q. Zhang, H. Kong, C. Gu, C. Li, Z. Bu, Y. Kawaoka*, H. Chen* (2016). Prevalence, genetics, and transmissibility in ferrets of Eurasian avian-like H1N1 swine influenza viruses. Proceedings of National Academy of Sciences USA, 113(2), 392-397. 10) X. Feng, Z. Wang, J. Shi, G. Deng, H. Kong, S. Tao, C. Li, L. Liu, Y. Guan, and H. Chen*(2016). Glycine at position 622 in PB1 contributes to the virulence of H5N1 avian influenza virus in mice. Journal of Virology, 90(4): 1872-1979. 11) L. Liang, G. Deng, J. Shi, S. Wang, Q. Zhang, H. Kong, C. Gu, Y. Guan, Y. Suzuki, Y. Li, Y. Jiang, G. Tian, L. Liu, C. Li*, H. Chen* (2016). Genetics, Receptor Binding, Replication, and Mammalian Transmission of H4 Avian Influenza Viruses Isolated from Live Poultry Markets in China. Journal of Virology, 90(3): 1455-1469.Yang M, et al., Parasitology. Functional characterization of X-prolyl aminopeptidase from Toxoplasma gondii.2016 Sep;143(11):1443-9. doi: 10.1017/S0031182016000986. Epub 2016 May 25. 12) Zheng J et al., Characterization of aspartyl aminopeptidase from Toxoplasma gondii.sci Rep. 2016 Sep 28;6:34448. 13) Dang G, et al., Characterization of Rv0888, a Novel Extracellular Nuclease from Mycobacterium tuberculosis. Sci Rep. 2016 Jan 8;6:19033. 8 OIE Collaborating Centres Reports Activities, 2016

Zoonoses of Asia- - Harbin Veterinary Research Institute 14) Zhao Y, et al.,passive immunotherapy for Respiratory Syndrome coronavirus infection with equine immunoglobulin or immunoglobulin fragments in a mouse model. Antiviral Res. 2017 Jan;137:125-130. 15) Wang J et al.. Newcastle disease virus-vectored West Nile fever vaccine is immunogenic in mammals and poultry. Virol J. 2016 Jun 24;13:109. doi: 10.1186/s12985-016-0568-5. b) International conferences: 3 1)Hualan Chen presented Threats to public health posed by animal influenza viruses on March 22, 2016 at the French Academy of Sciences, Paris 2)Hualan Chen presented Characterization of the low pathogenic animal influenza viruses isolated in China at the CEIRS Annual Network Meeting on June 26th, 2016 at Memphis, USA 3)Yanbing Li presented Epidemiology and control strategy for HPAI in China, on May 11th, in Seoul Korea; The dignosis for HPAI in China on May 12th, in Anyang, Korea, respectively, at KIST-Konkuk ORP workshop for on-site diagnosis and HTS system for Avian Influenza, cohosted by Korea Institute of Science and Technology and Korea Konkuk University. c) National conferences: 10 1) Hualan Chen presented Threat to human public health posed by animal influenza viruses at the Nature Conference: Viral Infection and Immune Response on Oct. 23, 2016 in Wuhan, China 2) Hualan Chen presented Research and control of avian influenza viruses at The Belt and Road + Modern Agriculture International Forum, on Oct. 31, 2016 in Beijing, China 3) Hualan Chen presented Threat to human public health posed by neglected animal influenza viruses at the World Life Science Conference: Forum on Women in Life Science on Nov. 1st, 2016 in Beijing, China 4) Hualan Chen presented Characterization of avian influenza viruses World Life Science Conference: Infection and Immunity on Nov. 2st, 2016 in Beijing, China 5) Chengjun Li presented The research and control of avian influenza at the Techtronic Expo 2016 (National Scientific and Technological Innovation Achievements Exhibition) on Sept. 25, 2016 in Hong Kong, China 6) Chengjun Li presented The research and control of avian influenza at the National Scientific and Technological Innovation Achievements Exhibition on Oct. 12, 2016 in Macau, China 7) Guohua Deng presented Surveillance of avian influenza infection in free roaming water flow in Hunan and Hubei province at the Annual Academic Congress of Chinese Association of Animal Science and Veterinary Medicine on Sept. 5-8,2016 in Beijing, China. 8) Chengjun Li presented The public health threat posed by neglected animal influenza virus at the 12th symposium of the Chinese society of immunology on Oct. 21-22, 2016 in Kunming, China. 9) Huanliang Yang presented The knowledge on swine influenza viruses at National Congress on Biotechnology 2016 on the 10th conference of the Chinese bioengineering society and National biotechnology conference 2016 on Aug.12, 2016 in Harbin, China. 10) Guohua Deng presented Surveillance of avian influenza infection in free roaming water flow in Hunan and Hubei province between 2011-2015 at the 8th Academic symposium of Chinese Animal Husbandry and Veterinary Young Scientists on Nov. 15-18,2016 in Shaoxing, Zhejiang Province, China. d) Other (Provide website address or link to appropriate information): 2 www.hvri.ac.cn http://en.linktads.com/ OIE Collaborating Centres Reports Activities, 2016 9