Yerkes, 954 Gatewood Road, Room 1024
Atlanta, GA 30329
Scientist, Emory Vaccine Center
Affiliate Scientist, Yerkes National Primate Research Center
B.S. Biology, Georgia State University, Atlanta, GA, 1982 - 1987
Ph.D. Biochemistry and Molecular Genetics, Georgia State University, Atlanta, GA, 1987 - 1994
The extraordinary genetic diversity of global human immunodeficiency virus type 1 (HIV-1) strains, especially within the envelope (Env) glycoproteins, is a force to be reckoned with regards to vaccine design. However most current strategies simply ignore this problem by focusing on one or a few viral strains. It has also become painfully clear that vaccines designed to elicit cell-mediated immunity without an antibody-inducing component are not protective or beneficial, bringing the conundrum of how to elicit broadly protective neutralizing antibodies against HIV-1 Env back into the forefront. In our research, we have continued to focus on individuals in Africa that are infected with the globally predominant HIV-1 subtypes, such as A and C. We have recently begun to uncover differences between the HIV-1 subtypes within the Env glycoproteins, which are highly variable in sequence and are the major targets for neutralizing antibodies. These differences have the potential to impact the selection and design of vaccine immunogens. Our major approach is to determine how subtype C HIV-1 is neutralized by autologous antibodies in Zambian individuals, and how the virus subsequently escapes, in the context of the viral diversity in which these processes occur. Remarkably, these processes remain poorly understood. We do this by analyzing in detail samples collected longitudinally from newly infected individuals in Zambia, from acute/early infection into the chronic phase, to understand how the hyper-variable and structural domains of the Env glycoproteins evolve as the immune response struggles to contain viral replication. We are also generating monoclonal antibodies from these patients, which will allow for a more precise reconstruction of the early events involved in neutralization and viral escape. Recently, we have extended these same approaches to identify chronically subtype C infected patients that produce neutralizing antibodies with cross-neutralizing activity against heterologous Envs from other subjects, and will define the 'conserved' neutralizing antibody targets in these individuals. We have also characterized the neutralizing antibody and B cell response in a natural host for simian immunodeficiency virus (SIV), the sooty mangabey, leading to a better understanding of how this African nonhuman primate avoids AIDS-like disease despite high levels of virus replication. Collectively, these studies will provide (i) much needed information about how a vaccine might induce a protective neutralizing antibody response, and (ii) a better understanding of the pathogenic consequences of neutralizing antibodies, which force the virus to diversify from a homogeneous population after infection to a highly heterogeneous, complex viral quasispecies that is unique to each patient.
Permanent member, NIH/NIAID Study Section, AIDS Immunology and Pathogenesis, 2008-2012
Scholar Award, amfAR, 2000-2002
John R. Durant Excellence in Cancer Research, 1998
John R. Durant Excellence in Cancer Research, 1997
R.M. Lynch, T.Y. Shen, S. Gnanakaran, and C.A. Derdeyn. (2009). Appreciating HIV-1 Diversity: Subtype Differences in Env. AIDS Res. Hum. Retroviruses: in press.
R.E. Haaland, P.A. Hawkins, J. Salazar-Gonzalez, A. Johnson, A. Tichacek, E. Karita, O. Manigart, J. Mulenga, B.F. Keele, G.M. Shaw, B.H. Hahn, S.A. Allen, C.A. Derdeyn, and E. Hunter. (2009) Inflammatory genital infections mitigate a severe genetic bottleneck in heterosexual transmission of subtype A and C HIV-1. PLoS Pathog. 5(1):Epub.
J. Salazar-Gonzalez, K.T. Pham, E. Bailes, M.G. Salazar, B.F. Keele, C.A. Derdeyn, P. Farmer, E. Hunter, S. Allen, J. Anderson, R. Swanstrom, G.S. Athreya, B.T.M. Korber, G.M. Shaw, P.M. Sharp, and B.H. Hahn. (2008) Deciphering HIV-1 Transmission and Early Envelope Diversification by Single Genome Amplification and Sequencing. J. Virol 82(8): 3952-70.
P.A. Goepfert, W. Lumm, P. Farmer, A. Prendergrast, P. Matthews, J. Carlson, C.A. Derdeyn, J. Tang, R.A. Kaslow, K. Yusim, D. Heckerman, J.Mulenga, S. Allen, P. Goulder, and E. Hunter. (2008) Donor HIV-1 Escape through Gag Reduces Viral Fitness after New Host Transmission. J. Exp. Med. 205 (5): 1009-17.
C.A. Derdeyn and E. Hunter. 2008. Viral Characteristics of Transmitted HIV. Current Opinion in HIV and AIDS 3 (1):16-21.
R. Rong, S. Gnanakaran, J.M. Decker, J.N. Sfakianos, F. Bibollet-Ruche, J.L. Mokili, M. Muldoon, J. Mulenga, S. Allen, B.H. Hahn, G.M. Shaw, J.L. Blackwell, E. Hunter, B.T. Korber, and C.A. Derdeyn. (2007) Unique Mutational Patterns in the Envelope a2 Amphipathic Helix are Associated with Resistance to Autologous Neutralization of Subtype C HIV-1. J. Virol: 81 (11): 5658-68.
S. Gnanakaran, D. Lang, M. Daniels, T. Battacharya, C.A. Derdeyn, and B.T. Korber. (2007) Clade Specific Differences in HIV-1: Diversity and Correlations in the C3-V4 Regions of gp120. J. Virol: 81 (9): 4886-91.
R. Rong, F. Bibollet-Ruche, J. Mulenga, S. Allen, J.L. Blackwell, and C.A. Derdeyn. (2007) The Role of V1V2 and ther HIV-1 Envelope Domains in Resistance to Autologous Neutralization During Clade C HIV-1 Infection. J. Virol. 81 (3): 1350-1359.
M.A. Brockman, A. Schneidewind, M. Lahaie, A. Schmidt, T. Miura, I. DeSouza, F. Ryvkin, C.A. Derdeyn, S. Allen, E. Hunter, J. Mulenga, P.A. Goepfert, B.D. Walker, and T.M. Allen. (2007) Escape and Compensation from Early HLA-B57-mediated CTL Pressure on HIV-1 Gag Alters Capsid Interactions with Cyclophilin A. J. Virol. 81(22): 12608-18.
M. Li, J.F. Salazar-Gonzalez, C.A. Derdeyn, L. Morris, C. Williamson, J.E. Robinson, J.M. Decker, Y. Li, M.G. Salazar, V.R. Polonis, K. Mlisana, S.A. Karim, K. Hong, K.M. Greene, M. Bilska, J. Zhou, S. Allen, E. Chomba, J. Mulenga, C. Vwalika, F. Gao, M. Zhang, B.T. Korber, E. Hunter, B.H. Hahn, and D.C. Montefiori. (2006) Genetic and Neutralization Properties of Acute and Early Subtype C HIV-1 Molecular Env Clones from Heterosexually Acquired Infections in Southern Africa. Journal of Virology 80 (23): 11776-90.
B. Li, J.M. Decker, R.W. Johnson, F. Bibollet-Ruche, X. Wei, J. Mulenga, S. Allen, E. Hunter, B.H. Hahn, G.M. Shaw, J.L. Blackwell, and C.A. Derdeyn. (2006) Evidence for Potent Autologous Neutralizing Antibody Titers and Compact Envs in Early Infection with Subtype C HIV-1. Journal of Virology 80 (11):5211-5218.
R.W. Johnson, S. Sunay, J. Mulenga, S. Allen, and C.A. Derdeyn. (2006). Real-time PCR Quantitation of Subtype C HIV DNA in a Zambian Discordant Couple Cohort. AIDS Research and Human Retroviruses May 22(5): 438-44.
C.A. Derdeyn and G. Silvestri. 2005. Viral and Host Factors in the Pathogenesis of HIV Infection. Current Opinion in Immunology (17): 1-8.
C.A. Derdeyn, J.M. Decker, F. Bibollet-Ruche, J. L. Mokili, M. Muldoon, S.A. Denham, M.L. Heil, J.Y. Lee, F. Kasolo, R. Musonda, B.H. Hahn, G.M. Shaw, B. T. Korber, S. Allen and E. Hunter. (2004) Envelope-Constrained, Neutralization-Sensitive HIV-1 Following Heterosexual Transmission. Science 303(5666):2019-2022.
M.L. Heil, J.M. Decker, D.T. Chen, J.N. Sfakianos, G.M. Shaw, E. Hunter, and C.A. Derdeyn. (2004) Determinants of HIV-1 Baseline Sensitivity to the Fusion Inhibitors Enfuvirtide and T-649 Reside Outside of the Peptide Interaction Site. Journal of Virology 78 (14): 7582-7589.
C.A. Derdeyn, J.M. Decker, J.N. Sfakianos, Z. Zhang, W.A. O'Brien, L. Ratner, G.M. Shaw, and E. Hunter. (2001) Sensitivity of HIV-1 to the Fusion Inhibitors T-649 and T-20 is Modulated by Coreceptor Specificity and Involves Distinct Regions of gp41. Journal of Virology 75(18): 8605-8614
Derdeyn, C.A., J. M. Decker, J. N. Sfakianos, X. Wu, W. A. O'Brien, L. Ratner, J. C. Kappes, G. M. Shaw, and E. Hunter. (2000) Sensitivity of HIV-1 to the Fusion Inhibitor T-20 is Modulated by Coreceptor Specificity Defined by the V3 loop of gp120. Journal of Virology 74(18): 8358-8367
Derdeyn, C.A., J.M. Kilby, G.D. Miralles, G. Sfakianos, L.F. Li, M.S. Saag, R.D. Hockett, and R.P.Bucy. (1999) Evaluation of Distinct Blood Lymphocyte Populations in Human Immunodeficiency Type 1-infected Subjects in the Absence or Presence of Effective Therapy. Journal of Infectious Diseases 180:1851-62
Derdeyn, C.A., C. Costello, J.M. Kilby, G. Sfakianos, M.S. Saag, R. Kaslow, and R. P. Bucy. (1999) Correlation Between Circulating Stromal Cell Derived Factor 1 Levels and CD4+ Cell Count in Human Immunodeficiency Type-1 Infected Individuals. AIDS Research and Human Retroviruses 15(12):1063-1071
C.A. Derdeyn and E. Hunter. 2004. Entry Inhibitors and Beyond. In: HIV Chemotherapy: A Critical Review, Ed. Sal Butera, Horizon Scientific Press, Norfolk, U.K.
Entry Inhibitors in HIV Therapy. Eds. J.D. Reeves and C.A. Derdeyn. In the Milestones in Drug Therapy series, Birkhauser Publishing, Switzerland