Antibodies and Infectious Disease
Mei-Yun Zhang, PhD
Assistant Professor, AIDS Institute
BA, MSc (China Agricultural University); PhD (Aachen University)
Tel: (852) 2818 3685; Fax: (852) 2817 7805
Office: Room 45A, 5/F, Laboratory Block, 21 Sassoon Road, Pokfulam
Member, Editorial Board, Journal of Bioanalysis & Biomedicine (2009-present)
Member, Editorial Board, Journal of Bioequivalence & Bioavailability (2009-present)
Member, American Society for Virology (ASV)
Member, Chinese Biopharmaceutical Association (CBA)
Federal Technology Transfer Award, National Cancer Institute, NIH (2002-2008)
Outstanding Performance Award, SAIC, National Cancer Institute at Frederick (2004)
Vaccination has offered protection against a number of viral pathogens, but accumulating evidence has showed that conventional vaccine approaches are not applicable to all viral infections. More understanding of the immune system and the immune response to viral infection is required. We are focused on the interplay of antibodies and viruses in humans, and in particular, the highly mutable viruses, human immunodeficiency virus type 1 (HIV-1) and influenza virus. We have been developing broadly cross-reactive neutralizing antibodies to these viruses to explore the anti-viral activity of antibodies in vitro and in vivo and to define molecular targets for rational vaccine design.
Cancer neutralizing antibodies have been successful in treatment of breast cancer. We are also interested in investigating cancer-related proteins and their signaling network and developing antibody-based cancer therapeutics.
Zhang M-Y, Rosa Borges A, Ptak RG, Mankowski MK, Wang Y, Dimitrov AS, Alam M, Wieczorek L, Bouma P, Fouts T, Jiang S, Polonis VR, Haynes BF, Quinnan GV, Montefiori DC, Dimitrov DS. Potent and Broad Neutralizing Activity of a Single Chain Antibody Fragment against Cell-Free and Cell-Associated HIV-1. MAbs (in press)
Chen L., Do Kwon Y, Zhou T, Wu X, O’Dell S, Hessell AJ, Tang M, Xu L, Yang Z-Y, Zhang M-Y, Arthos J, Burton DR, Dimitrov DS, Nabell GJ, Ponser M, Sodroski J, Wyatt R, Mascola JR, Kwong PD. Structural basis of immune evasion at the site of CD4 attachment on HIV-1 gp120. Science 326: 1123, 2009.
Zhang M-Y, Feng Y, Wang Y, Dimitrov DS. Characterization of a chimeric monoclonal antibody against the Insulin-like Growth Factor-I Receptor. MAbs, 1(5): 475-480, 2009.
Xiao X, Chen W, Feng Y, Zhu Z, Prabakaran P, Wang Y, Zhang M-Y, Longo NS, Dimitrov DS. Germline-like predecessors of broadly neutralizing antibodies lack measurable binding to HIV-1 envelope glycoproteins: Implications for evasion of immune responses and design of vaccine immunogens. Biochem Biophys Res Commun. 390 (3):404-9, 2009.
Zhang M-Y, Dimitrov DS. Sequential Antigen Panning for Selection of Broadly Cross-Reactive HIV-1-Neutralizing Human Monoclonal Antibodies. Methods Mol Biol. 562:143-54, 2009.
Zhang M-Y, Dimitrov DS. Competitive antigen panning for selection of HIV-1 neutralizing human monoclonal antibodies specific for gp41. Methods Mol. Biol. 525:175-86, 2009.
Zhang M-Y, Wang Y, Mankowski MK, Ptak RG, Dimitrov DS. Cross-reactive HIV-1-neutralizing activity of serum IgG from a rabbit immunized with gp41 fused to IgG1 Fc: Possible role of the prolonged half-life of the immunogen. Vaccine 27(6): 857-863, 2009.
Zhang M-Y, Vu BK, Choudhary A, Lu H, Humbert M, Ong H, Alam M, Ruprecht R, Quinnan G, Jiang S, Montefiori D, Mascola JR, Broder CC, Haynes BF, Dimitrov DS. Cross-reactive human immunodeficiency virus type 1-neutralizing human monoclonal antibody which recognizes a novel conformational epitope on gp41 and lacks reactivity against self antigens. J. Virol. 82(14):6869-79, 2008
Polonis VR, Brown BK, Rosa Borges A, Zolla-Pazner S, Dimitrov DS, Zhang M-Y, Barnett SW, Ruprecht RM, Scarlatti G, Fenyö E-M, Montefiori DC, Cutchan FE, Michael NL. Recent advances in the characterization of HIV-1 neutralization assays for standardized evaluation of the antibody response to infection and vaccination (mini-review). Virology. 375(2):315-20, 2008
Zhou T, Xu L, Dey B, Hessell AJ, Van Ryk D, Xiang SH, Yang X, Zhang M-Y, Zwick MB, Arthos J, Burton DR, Dimitrov DS, Sodroski J, Wyatt R, Nabel GJ, Kwong PD. Structural definition of a conserved neutralization epitope on HIV-1 gp120. Nature 445(7129):732-737, 2007
Choudhry V#, Zhang M-Y#, Sidorov IA, Bouma P, Cham F, Choudhary A, Rybak SM, Montefiori DC, Broder CC, Quinnan Jr. GV, Dimitrov DS. Cross-Reactive Monoclonal Antibodies Selected by Screening of an Immune Human Phage Library against an Envelope Glycoprotein (gp140) Isolated from a Patient (R2) with Broadly HIV-1 Neutralizing Antibodies. Virology 363(1):79-90, 2007 (# Co-first author)
Zhang M-Y, Dimitrov DS. Novel approaches for identification of broadly cross-reactive HIV-1 neutralizing human monoclonal antibodies and improvement of their potency (review). Current Pharmaceutical Design 13:203-212, 2007
Zhang M-Y, Choudhry V, Sidorov IA, Tenev V, Vu BK, Choudhary A, Lu H, Stiegler GM, Katinger HWD, Jiang S, Broder CC, Dimitrov DS. Selection of a novel gp41-specific HIV-1 neutralizing human antibody by competitive antigen panning. J. Immunol. Methods 317:21-30, 2006
Zhang M-Y, Vu B, Huang CC, Sidorov I, Choudhry V, Kwong PD, Dimitrov DS. Identification of human monoclonal antibodies specific for CCR5 from an antibody library derived from HIV-infected long-term non-progressors. Retrovirology, 2006, 3 Suppl 1:S61
Choudhry V, Zhang M-Y, Harris I, Sidorov IA, Vu B, Dimitrov AS, Fouts T, Dimitrov DS. Increased efficacy of HIV-1 neutralization by antibodies at low CCR5 surface concentration. Biochem. Biophys. Res. Commun. 348(3):1107-1115, 2006
Choudhry V, Zhang M-Y, Dimitrova D, Prabakaran P, Dimitrov AS, Fouts TR, Dimitrov DS. Antibody-based Inhibitors of HIV Infection (review). Expert. Opin. Biol. Ther. 6(5):523-531, 2006
Prabakaran P, Gan J, Wu Y-Q, Zhang M-Y, Dimitrov DS, Ji X. Structural mimicry of CD4 by a cross-reactive HIV-1 neutralizing antibody with CDR-H2 and H3 containing unique motifs. J. Mol. Biol. 357(1):82-99, 2006
Zhu Z, Dimitrov AS, Bossart KN, Crameri G, Bishop KA, Choudhry V, Mungall BA, Feng Y-R, Choudhary A, Zhang M-Y, Feng Y, Wang L-F, Xiao X, Eaton BT, Broder CC, Dimitrov DS. Potent neutralization of hendra and nipah viruses by human monoclonal antibodies. J. Virol. 80(2):891-899, 2006
Zhang M-Y, Choudhry V, Xiao X, Dimitrov DS. Human monoclonal antibodies to the S glycoprotein and related proteins as potential therapeutics for SARS (review). Curr. Opin. Mol. Ther. 7(2):151-156, 2005
Huang CC, Tang M, Zhang M-Y, Majeed S, Montabana E, Stanfield RL, Dimitrov DS, Korber B, Sodroski J, Wilson IA, Wyatt R, Kwong PD. Structure of a V3-containing HIV-1 gp120 core. Science 310:1025-1028, 2005
Zhang M-Y, Xiao X, Sidorov IA, Choudhry V, Cham F, Shang PF, Bouma P, Zwick M, Choudhary A, Montefiori DC, Broder CC, Burton DR, Quinnan GV Jr, Dimitrov DS. Identification and characterization of a new cross-reactive human immunodeficiency virus type 1-neutralizing human monoclonal antibody. J. Virol. 78(17):9233-9242, 2004
Zhang M-Y, Shu Y, Sidorov I, Dimitrov DS. Identification of a novel CD4i human monoclonal antibody Fab that neutralizes HIV-1 primary isolates from different clades. Antiviral Res. 61(3):161-164, 2004
Zhang M-Y, Shu Y, Rudolph D, Prabakaran P, Labriji AF, Zwick MB, Lal RB, Dimitrov DS. Improved breadth and potency of an HIV-1-neutralizing human single-chain antibody by random mutagenesis and sequential antigen panning. J. Mol. Biol. 335(1):209-219, 2004
Huang C-C, Venturi M, Majeed S, Moore MM, Phogat S, Zhang M-Y, Dimitrov DS, Hendrickson WA, Robinson J, Sodroski J, Wyatt R, Choe H, Farzan M, Kwong PD. Structural basis of tyrosine sulfation and VH-gene usage in antibodies that recognize the HIV-1 coreceptor binding site on gp120. Proc. Natl. Acad. Sci. 101(9):2706-2711, 2004
Darbha R, Phogat S, Labrijn AF, Shu Y, Gu Y, Andrykovitch M, Zhang M-Y, Pantophlet R, Vita C, Burton DR, Dimitrov DS, Ji, X. Crystal structure of the broadly cross-reactive HIV-1 neutralizing Fab X5 and fine mapping of it's epitope. Biochemistry 43(6):1410-1417, 2004
Zhang M-Y, Shu Y, Phogat S, Xiao X, Cham F, Bouma P, Choudhary A, Feng Y-R, Sanz I, Rybak S, Broder CC, Quinnan Jr. GV, Evans T, Dimitrov DS. Broadly cross-reactive HIV neutralizing human monoclonal antibody Fab selected by sequential antigen panning of a phage display library. J. Immunol. Methods 283(1-2):17-25, 2003
Moulard M, Phogat S, Shu Y, Xiao X, Binley JM, Zhang M-Y, Robinson J, Parren PWHI, Burton DR, Dimitrov DS. Broadly cross-reactive neutralizing human monoclonal antibody to HIV-1 selected for binding to gp120-CD4-CCR5 complexes. Proc. Natl. Acad. Sci. 99 (10):6913-6918, 2002
Zhang M-Y, Schillberg S, Zimmermann S, Breuer G, Liao Y-C, Fischer R. GST fusion proteins cause false positives during selection of viral movement protein specific single chain antibodies. J. Virol. Methods 91(2):139-147, 2001
Schillberg S, Zimmermann S, Zhang M-Y, Fischer R. Antibody-based resistance to plant pathogens (review). Transgenic Research 10:1-12, 2001
Zhang M-Y, Schillberg S, Prins M, Fischer R. Optimizing expression of a rare codon-rich viral protein in Escherichia coli using the IMPACT system. Analytical Biochemistry 271:202-204, 1999
Immunoglobulin having particular framework scaffold and methods of making and using. PCT/US02/29003, European Patent: EP1434800
Broadly cross-reactive neutralizing antibodies against Human Immunodeficiency Virus selected by Env-CD4-co-receptor complexes. PCT/US02/33165, US patent: 7,223,844
Human immunodeficiency virus-neutralizing human antibodies with improved breadth and potency. PCT/US03/14095. US patent: 7,566,451