UNDERSTANDING THE ADAPTIVE IMMUNE RESPONSES AGAINST NEWLY EMERGED VIRUSES, SARS CORONAVIRUS AND AVIAN H5N1 INFLUENZA VIRUS OH HSUEH LING, JANICE (Master of Science), NUS A THESIS SUBMITTED FOR THE DEGREE OF DOCTOR OF PHILOSOPHY DEPARTMENT OF MICROBIOLOGY NATIONAL UNIVERSITY OF SINGAPORE 2010 Acknowledgements I would like to sincerely thank my main supervisor, Dr Tan Yee Joo and co-supervisor Prof Michael Kemeny for their valuable guidance throughout the course of my PhD studies. I would also like to extend my thanks to my PhD committee members, Prof Hong Wan Jin and Dr Hwang Le-Ann for their advice. Special thanks to Dr Ali Mirazimi and his lab members, in particular Dr Sara Akerstrom, for their help in the H5N1 infectious studies done in BSL4 facilities in the Department of Microbiology, Tumor and Cell Biology, Karolinska Institute. For the collaboration work on SARS memory T cell response, I would like to thank Prof Antonio Bertoletti and his lab members from the Singapore Institute of Clinical Sciences for all the help and guidance and Dr Leong Hoe Nam and Dr Ling Khoon Lin from the Singapore General Hospital for kindly providing patient samples. I thank Dr Sunil K. Lal, International Centre for Genetic Engineering and Biotechnology, India and Dr Q. Duong Hong, Institute of Biotechnology, Hanoi, Vietnam, and Falko G. Falkner, Baxter Bioscience, Austria for providing H5N1 virus-derived DNA constructs and Prof Vincent T. K. Chow, NUS, Singapore for providing H3N2 virus-derived DNA constructs. I also thank Dr Alexander N. Zakhartchouk, University of Saskatchewan, Canada for providing the human adenovirus vector and Mia Brytting, Swedish Institute for Infectious Disease Control and Mikael Berg and Siamak Zohari, Swedish National Veterinary Institute, Sweden for providing the H5N1 influenza A viruses isolated in Sweden. I also thank Prof Chan Soh Ha, NUS, Singapore for providing the Epstein-Barr virus transformed lymphoblastoid B cell lines and Dr Gijsbert Grotenbreg’s laboratory, NUS, Singapore for performing the HLA typing of the SARS individuals. To all fellow laboratory members, past and present, in the Collaborative Anti-Viral Research group from the Institute of Molecular and Cell Biology, my deepest thanks for all your help and encouragement. Last but not least, sincere appreciation and thanks to my family for their patience and support all these years. Author’s publications 1. Hsueh-Ling Janice Oh, Sara Akerstrom, Shuo Shen, Sandor Bereczky, Helen Karlberg, Jonas Klingstrom, Sunil K. Lal, Ali Mirazimi, and Yee Joo Tan. (2010). An antibody against a novel and conserved epitope in the hemagglutinin subunit neutralizes numerous H5N1 influenza viruses. Journal of Virology. 84(16): 8275-8286. 2. Shuo Shen, Geetha Madadevappa, Hsueh-Ling Janice Oh, Boon Yu Wee, Yook-Wah Choi, Le-Ann Hwang, Seng Gee Lim, Wanjin Hong, Sunil K. Lal, and Yee Joo Tan. (2008). Comparing the antibody responses against recombinant hemagglutinin proteins of avian influenza A (H5N1) virus expressed in insect cells and bacteria. Journal of Medical Virology. 80: 1972-1983. . UNDERSTANDING THE ADAPTIVE IMMUNE RESPONSES AGAINST NEWLY EMERGED VIRUSES, SARS CORONAVIRUS AND AVIAN H5N1 INFLUENZA VIRUS OH HSUEH LING, JANICE (Master of Science), NUS A THESIS. Jonas Klingstrom, Sunil K. Lal, Ali Mirazimi, and Yee Joo Tan. (2 010 ). An antibody against a novel and conserved epitope in the hemagglutinin 1 subunit neutralizes numerous H5N1 influenza viruses Joo Tan. (2008). Comparing the antibody responses against recombinant hemagglutinin proteins of avian influenza A (H5N1) virus expressed in insect cells and bacteria. Journal of Medical Virology.