Monoclonal Antibody Unit

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	Yee Joo TAN
	Lab Location: #6-04 email: mcbtanyj@imcb.a-star.edu.sg tel: 65869625
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	Key Publications
	Lee VJ, Tay JK, Chen MI, Phoon MC, Xie ML, Wu Y, Lee CX, Yap J, Sakharkar KR, Sakharkar MK, Lin RT, Cui L, Kelly PM, Leo YS, Tan YJ, Chow VT. Inactivated trivalent seasonal influenza vaccine induces limited cross-reactive neutralizing antibody responses against 2009 pandemic and 1934 PR8 H1N1 strains. Vaccine. 2010 Oct 4;28(42):6852-7. Oh HL, Akerström S, Shen S, Bereczky S, Karlberg H, Klingström J, Lal SK, Mirazimi A, Tan YJ. An antibody against a novel and conserved epitope in the hemagglutinin 1 subunit neutralizes numerous H5N1 influenza viruses. J Virol. 2010 Aug;84(16):8275-86. Tan Z, Akerstrom S, Wee BY, Lal SK, Mirazimi A, Tan YJ. A new panel of NS1 antibodies for easy detection and titration of influenza A virus. J Med Virol. 2010 Mar;82(3):467-75. Shen S, Mahadevappa G, Oh HL, Wee BY, Choi YW, Hwang LA, Lim SG, Hong W, Lal SK, Tan YJ. Comparing the antibody responses against recombinant hemagglutinin proteins of avian influenza A (H5N1) virus expressed in insect cells and bacteria. J Med Virol. 2008 Nov;80(11):1972-83. Lip KM, Shen S, Yang X, Keng CT, Zhang A, Oh HL, Li ZH, Hwang LA, Chou CF, Fielding BC, Tan TH, Mayrhofer J, Falkner FG, Fu J, Lim SG, Hong W, Tan YJ. Monoclonal antibodies targeting the HR2 domain and the region immediately upstream of the HR2 of the S protein neutralize in vitro infection of severe acute respiratory syndrome coronavirus. J Virol. 2006 Jan;80(2):941-50. Akerström S, Tan YJ, Mirazimi A. (equal contributing authors) Amino acids 15-28 in the ectodomain of SARS coronavirus 3a protein induces neutralizing antibodies. FEBS Lett.* 2006 Jul 10;580(16):3799-803. Keng CT, Zhang A, Shen S, Lip KM, Fielding BC, Tan TH, Chou CF, Loh CB, Wang S, Fu J, Yang X, Lim SG, Hong W, Tan YJ. Amino acids 1055 to 1192 in the S2 region of severe acute respiratory syndrome coronavirus S protein induce neutralizing antibodies: implications for the development of vaccines and antiviral agents. J Virol. 2005 Mar;79(6):3289-96. Tan YJ, Goh PY, Fielding BC, Shen S, Chou CF, Fu JL, Leong HN, Leo YS, Ooi EE, Ling AE, Lim SG, Hong W.Profiles of antibody responses against severe acute respiratory syndrome coronavirus recombinant proteins and their potential use as diagnostic markers. Clin Diagn Lab Immunol. 2004 Mar;11(2):362-71. Tan YJ, Lim SP, Ting AE, Goh PY, Tan YH, Lim SG, Hong W. An anti-HIV-1 gp120 antibody expressed as an endocytotic transmembrane protein mediates internalization of HIV-1. Virology. 2003 Oct 10;315(1):80-92.
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			Yee Joo TAN
			Yee Joo Tan obtained her PhD from the University of Cambridge in 1997. She joined IMCB thereafter as a postdoctoral research fellow and is now a Principal Investigator (joint appointment) and group leader of the Monoclonal Antibody Unit (MAU). She concurrently holds an Associate Professor position at the Department of Microbiology, Yong Loo Lin School of Medicine, National University Health System (NUHS), National University of Singapore. (Please see http://www.med.nus.edu.sg/mbio/staff-t_yeejoo.html).

			Monoclonal antibodies for research, diagnostic and therapeutic applications
			Antibodies are reagents commonly used in different areas of biomedical research as well as diagnostic and therapeutic applications. The monoclonal antibody unit (MAU) uses monoclonal antibodies as tools to characterize and combat RNA viruses that can infect and cause severe diseases in human. Currently, we are working on the severe acute respiratory syndrome coronavirus (SARS-CoV), hepatitis C virus (HCV) and influenza A virus. For example, we have generated and characterized a potent neutralizing antibody that binds the hemagglutinin (HA) protein of the H5N1 influenza A virus and blocks the entry of different clades of H5N1 into MDCK cells (Oh et al., J Virol. 2010 Aug;84(16):8275-86). This antibody was also shown to protect mice against lethal H5N1 viral challenge.



	Figure: Monoclonal antibody (MAb) 9F4 prevents viral entry and protects mice against lethal H5N1 viral challenge. (A) Pseudotyped lentiviral particles harboring the HA proteins from H5N1 influenza viruses of clade 1 (VN04-H5pp), clade 2.1 (Indo5-H5pp), and clade 2.2 (IND06-H5pp) were incubated with different concentrations of MAb 9F4 at 4°C for 2 h before inoculation onto MDCK cells. Luciferase activity in the cell lysates was determined 72 h postinfection. Viral entry, as indicated by the luciferase activity, was expressed as a percentage of the reading obtained in the absence of antibody (No Ab), which was set at 100%. A control MAb of the same isotype (IgG control) was used at the highest concentration tested. (B) To test for prophylactic efficacy, BALB/c mice were immunized either with MAb 9F4 at different doses, with an irrelevant IgG control MAb (1 mg/kg), or with PBS and were subjected to viral challenge with clade 2.3 H5N1 virus 24 h later. A group of mice was mock infected. Mice were observed daily for disease and mortality. Percentages of mice surviving are plotted against the days post infection. Monoclonal antibodies targeting viral proteins are also useful for the development of diagnostic kit. An ongoing project is titled "Piezoelectric surface acoustic wave (SAW) sensors for influenza diagnosis" and will be performed in collaboration with colleagues from Institute of Materials Research and Engineering (IMRE) and Bioinformatics Institute (BII). It is funded by a JCO Exploratory Grant led by Dr. YAO Kui, IMRE. In addition to viral research, MAU also participates in collaborative projects in the other areas of molecular diagnostics. Currently, we are collaborating with (a) Assoc Prof Zbynek Bozdech from the Nanyang Technological University to generate monoclonal antibodies that can be used to develop diagnostic kit for malaria; (b) Drs Seow Wan Tew, David Low and Winnie Fung from the KK Women's and Children's Hospital to develop sensitive antibodies for the detection of soluble c-kit in the bodily fluids of intracranial germinoma patients.