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George K Lewis
 

George K Lewis Ph.D.

Academic Title: Professor
Primary Appointment: Microbiology and Immunology
Additional Title(s): Co-Director, Division of Basic Science and Vaccine Research, Institute of Human Virology
glewis@ihv.umaryland.edu
Location: MRF, N660
Phone: (410) 706-4668

Research Interests:

Our laboratory is studying the relationships among antibody specificity, effector functions, and protective immunity in both HIV-1 infected humans and in a rhesus macaque vaccine model. We have developed methods to quantify memory B cell responses (BMem) at the clonal level that allow the capture of desired specificities as molecularly cloned monoclonal antibodies (mAbs). Using these methods we recently reported discordance between BMem and circulating antibodies for the HIV-1 envelope glycoprotein (Env) (1) in a population of HIV-1 infected people who control viremia to undetectable levels in the absence of anti-retroviral therapy (2-4). Monoclonal antibody analysis confirmed the presence of bona fide BMem specific for Env epitopes for which circulating antibodies were absent. These data illustrate the lack of persistent serological memory to HIV-1 Env in the absence of continuous antigenic stimulation, which is a serious problem in exploiting Env immuogens as HIV-1 vaccines. Studies are underway in our group to understand the mechanism of this defect with the long-term goal of increasing persistence of anti-Env antibody responses after vaccination (5).

In a related series of studies to probe the relationships between specificity and function, we are isolating Env-specific mAbs from HIV-1 infected people who have circulating antibodies that neutralize a broad array of HIV-1 isolates. We are also carrying out similar studies using non-human primates that control a SHIV challenge consequent to immunization with the conformationally constrained gp120 immunogen (FLSC) developed in collaboration with IHV colleagues (6, 7). These studies are ongoing, however, in addition to conventional neutralizing mAbs, we have also found a new category of non-neutralizing mAbs that mediate potent Fc-mediated effector function. A subset of these mAbs recognize epitopes that are selectively exposed during viral entry. We are evaluating these mAbs for specificity by epitope mapping and x-ray crystallography and ultimately by passive immunization in non-human primates to determine their protective efficacy. These studies will help delineate the relationships among specificity, effector function, and protective immunity to HIV-1.

Research Publications

Guan, Y., M.M. Sajadi, R. Kamin-Lewis, T.R. Fouts, A. Dimitrov, Z. Zhang, R.R. Redfield, A.L. DeVico, R.C. Gallo, and G.K. Lewis. 2009. Discordant memory B cell and circulating anti-Env antibody responses in HIV-1 infection. Proc Natl Acad Sci U S A 106:3952-3957.

Sajadi, M.M., N.T. Constantine, D.L. Mann, M. Charurat, E. Dadzan, P. Kadlecik, and R.R. Redfield. 2009. Epidemiologic characteristics and natural history of HIV-1 natural viral suppressors. J Acquir Immune Defic Syndr 50:403-408.

Sajadi, M.M., A. Heredia, N. Le, N.T. Constantine, and R.R. Redfield. 2007. HIV-1 natural viral suppressors: control of viral replication in the absence of therapy. Aids 21:517-519.

Sajadi, M.M., Y. Guan, A.L. DeVico, M.S. Seaman, M. Hossain, G.K. Lewis, and R.R. Redfield. 2011. Correlation between circulating HIV-1 RNA and broad HIV-1 neutralizing antibody activity. J Acquir Immune Defic Syndr 57:9-15.

Lewis, G.K. 2010. Challenges of antibody-mediated protection against HIV-1. Expert review of vaccines 9:683-687.

Fouts, T.R., R. Tuskan, K. Godfrey, M. Reitz, D. Hone, G.K. Lewis, and A.L. DeVico. 2000. Expression and characterization of a single-chain polypeptide analogue of the human immunodeficiency virus type 1 gp120-CD4 receptor complex. J Virol 74:11427-11436.

DeVico, A., T. Fouts, G.K. Lewis, R.C. Gallo, K. Godfrey, M. Charurat, I. Harris, L. Galmin, and R. Pal. 2007. Antibodies to CD4-induced sites in HIV gp120 correlate with the control of SHIV challenge in macaques vaccinated with subunit immunogens. Proc Natl Acad Sci U S A 104:17477-17482.


Grants & Contract:

Our laboratory is funded by grants from the National Institutes of Health and The Bill and Melinda Gates Foundation.


Publications:

Sajadi, M.M., Y. Guan, A.L. DeVico, M.S. Seaman, M. Hossain, G.K. Lewis, and R.R. Redfield. 2011. Correlation between circulating HIV-1 RNA and broad HIV-1 neutralizing antibody activity. J Acquir Immune Defic Syndr 57:9-15.

Lewis, G.K., T. Fouts, S. Ibrahim, J.B. Taylor, R. Salkar, Y. Guan, R. Kamin-Lewis, and A.L. DeVico. 2011. Identification and Characterization of an Immunogenic Hybrid Epitope Formed by Both HIV Gp120 and Human CD4 Proteins. Journal of Virology (in press)

Bagley, K.C., G.K. Lewis, and T.R. Fouts. 2011. Adjuvant activity of the catalytic A1 domain of cholera toxin for retroviral antigens delivered by GeneGun. Clin Vaccine Immunol 18:922-930.

Lewis, G.K. 2010. Challenges of antibody-mediated protection against HIV-1. Expert review of vaccines 9:683-687.

Monaco, A., F.M. Marincola, M. Sabatino, Z. Pos, M.L. Tornesello, D.F. Stroncek, E. Wang, G.K. Lewis, F.M. Buonaguro, and L. Buonaguro. 2009. Molecular immune signatures of HIV-1 vaccines in human PBMCs. FEBS Lett 583:3004-3008.

Guan, Y., M.M. Sajadi, R. Kamin-Lewis, T.R. Fouts, A. Dimitrov, Z. Zhang, R.R. Redfield, A.L. DeVico, R.C. Gallo, and G.K. Lewis. 2009. Discordant memory B cell and circulating anti-Env antibody responses in HIV-1 infection. Proceedings of the National Academy of Sciences of the United States of America 106:3952-3957.

Buonaguro, L., M.L. Tornesello, R.C. Gallo, F.M. Marincola, G.K. Lewis, and F.M. Buonaguro. 2009. Th2 polarization in peripheral blood mononuclear cells from human immunodeficiency virus (HIV)-infected subjects, as activated by HIV virus-like particles. Journal of Virology 83:304-313.

Lewis, G.K., Jr., W.L. Olbricht, and G.K. Lewis, Sr. 2008. Acoustically enhanced Evans blue dye perfusion in neurological tissues. J Acoust Soc Am 2:20001-200017.

Lewis, G.K., Jr., and W.L. Olbricht. 2008. Development of a portable therapeutic and high intensity ultrasound system for military, medical, and research use. Rev Sci Instrum 79:114302.

Lewis, G.K., Jr., G.K. Lewis, Sr., and W. Olbricht. 2008. Cost-effective broad-band electrical impedance spectroscopy measurement circuit and signal analysis for piezo-materials and ultrasound transducers. Meas Sci Technol 19:105102.

Guan, Y., S. Abdelwahab, R. Kamin-Lewis, A.L. DeVico, and G.K. Lewis. 2008. Self-protection of individual CD4+ T cells against R5 HIV-1 infection by the synthesis of anti-viral CCR5 ligands. PLoS ONE 3:e3481.

Buonaguro, L., A. Monaco, E. Arico, E. Wang, M.L. Tornesello, G.K. Lewis, F.M. Marincola, and F.M. Buonaguro. 2008. Gene expression profile of peripheral blood mononuclear cells in response to HIV-VLPs stimulation. BMC Bioinformatics 9 Suppl 2:S5.

Lewis, G.K. 2007. Live-attenuated Salmonella as a prototype vaccine vector for passenger immunogens in humans: are we there yet? Expert review of vaccines 6:431-440.

DeVico, A., T. Fouts, G.K. Lewis, R.C. Gallo, K. Godfrey, M. Charurat, I. Harris, L. Galmin, and R. Pal. 2007. Antibodies to CD4-induced sites in HIV gp120 correlate with the control of SHIV challenge in macaques vaccinated with subunit immunogens. Proceedings of the National Academy of Sciences of the United States of America 104:17477-17482.

Bagley, K.C., S.F. Abdelwahab, R.G. Tuskan, and G.K. Lewis. 2006. Cholera toxin indirectly activates human monocyte-derived dendritic cells in vitro through the production of soluble factors, including prostaglandin E(2) and nitric oxide. Clin Vaccine Immunol 13:106-115.

Popovic, M., K. Tenner-Racz, C. Pelser, H.J. Stellbrink, J. van Lunzen, G. Lewis, V.S. Kalyanaraman, R.C. Gallo, and P. Racz. 2005. Persistence of HIV-1 structural proteins and glycoproteins in lymph nodes of patients under highly active antiretroviral therapy. Proceedings of the National Academy of Sciences of the United States of America 102:14807-14812.

Bagley, K.C., S.F. Abdelwahab, R.G. Tuskan, and G.K. Lewis. 2005. Pasteurella multocida toxin activates human monocyte-derived and murine bone marrow-derived dendritic cells in vitro but suppresses antibody production in vivo. Infection and immunity 73:413-421.

Bagley, K.C., S.F. Abdelwahab, R.G. Tuskan, and G.K. Lewis. 2003. An enzymatically active a domain is required for cholera-like enterotoxins to induce a long-lived blockade on the induction of oral tolerance: new method for screening mucosal adjuvants. Infection and immunity 71:6850-6856.

Abdelwahab, S.F., F. Cocchi, K.C. Bagley, R. Kamin-Lewis, R.C. Gallo, A. DeVico, and G.K. Lewis. 2003. HIV-1-suppressive factors are secreted by CD4+ T cells during primary immune responses. Proceedings of the National Academy of Sciences of the United States of America 100:15006-15010.

Kamin-Lewis, R., S.F. Abdelwahab, C. Trang, A. Baker, A.L. DeVico, R.C. Gallo, and G.K. Lewis. 2001. Perforin-low memory CD8+ cells are the predominant T cells in normal humans that synthesize the beta -chemokine macrophage inflammatory protein-1beta. Proceedings of the National Academy of Sciences of the United States of America 98:9283-9288.

Finnegan, C.M., W. Berg, G.K. Lewis, and A.L. DeVico. 2001. Antigenic properties of the human immunodeficiency virus envelope during cell-cell fusion. Journal of Virology 75:11096-11105.

Carbonetti, N.H., R.G. Tuskan, and G.K. Lewis. 2001. Stimulation of HIV gp120-specific cytolytic T lymphocyte responses in vitro and in vivo using a detoxified pertussis toxin vector. AIDS research and human retroviruses 17:819-827.

Carbonetti, N.H., T.J. Irish, C.H. Chen, C.B. O'Connell, G.A. Hadley, U. McNamara, R.G. Tuskan, and G.K. Lewis. 1999. Intracellular delivery of a cytolytic T-lymphocyte epitope peptide by pertussis toxin to major histocompatibility complex class I without involvement of the cytosolic class I antigen processing pathway. Infection and immunity 67:602-607.

Burns, J.M., G.K. Lewis, and A.L. DeVico. 1999. Soluble complexes of regulated upon activation, normal T cells expressed and secreted (RANTES) and glycosaminoglycans suppress HIV-1 infection but do not induce Ca(2+) signaling. Proceedings of the National Academy of Sciences of the United States of America 96:14499-14504.

Burns, J.M., R.C. Gallo, A.L. DeVico, and G.K. Lewis. 1998. A new monoclonal antibody, mAb 4A12, identifies a role for the glycosaminoglycan (GAG) binding domain of RANTES in the antiviral effect against HIV-1 and intracellular Ca2+ signaling. The Journal of experimental medicine 188:1917-1927.

Morita, C.T., J.W. Goodman, and G.K. Lewis. 1985. Arsonate-specific murine T cell clones. II. Delayed-type hypersensitivity induced by P-azobenzenearsonate-L-tyrosine (ABA-Tyr). J Immunol 134:2894-2899.

Hornbeck, P.V., and G.K. Lewis. 1985. Idiotype connectance in the immune system. II. A heavy chain variable region idiotope that dominates the antibody response to the p-azobenzenearsonate group is a minor idiotope in the response to trinitrophenyl group. The Journal of experimental medicine 161:53-71.

Hornbeck, P.V., and G.K. Lewis. 1983. Idiotype connectance in the immune system. I. Expression of a cross-reactive idiotype on induced anti-p-azophenylarsonate antibodies and on endogenous antibodies not specific for arsonate. The Journal of experimental medicine 157:1116-1136.

Hertel-Wulff, B., J.W. Goodman, C.G. Fathman, and G.K. Lewis. 1983. Arsonate-specific murine T cell clones. I. Genetic control and antigen specificity. The Journal of experimental medicine 157:987-997.

Conger, J.D., E. Lamoyi, G.K. Lewis, A. Nisonoff, and J.W. Goodman. 1983. Idiotype profile of an immune response. II. Reversal of the relative dominance of major and minor cross-reactive idiotypes in arsonate-specific T-independent responses. The Journal of experimental medicine 158:438-451.

Conger, J.D., G.K. Lewis, and J.W. Goodman. 1981. Idiotype profile of an immune response. I. Contrasts in idiotypic dominance between primary and secondary responses and between IgM and IgG plaque-forming cells. The Journal of experimental medicine 153:1173-1186.

Chen, P., D.E. Nitecki, G.K. Lewis, and J.W. Goodman. 1980. Antigen structural requirements for immunoglobulin isotype switching in mice. The Journal of experimental medicine 152:1670-1683.

Lewis, G.K., J.W. Goodman, and R. Ranken. 1978. Activation of B cell subsets by T-dependent and T-independent antigens. Advances in experimental medicine and biology 98:339-356.

Lewis, G.K., and J.W. Goodman. 1978. Purification of functional, determinant-specific, idiotype-bearing murine T cells. The Journal of experimental medicine 148:915-924.

Lewis, G.K., and J.W. Goodman. 1977. Carrier-directed anti-hapten responses by B-cell subsets. The Journal of experimental medicine 146:1-10.

Lewis, G.K., R. Ranken, D.E. Nitecki, and J.W. Goodman. 1976. Murine B-cell subpopulations responsive to T-dependent and T-independent antigens. The Journal of experimental medicine 144:382-397.

Cruse, J.M., H.D. Whitten, G.K. Lewis, and E.S. Watson. 1973. Facilitation of macrophage-mediated destruction of allogeneic fibrosarcoma cells by tumor-enhancing IgG 2 in vitro. Transplantation proceedings 5:961-967.

Cruse, J.M., J.T. Forbes, G.Y. Gillespie, and G.K. Lewis. 1970. Immunologic enhancement induced by antibody fragments. Zeitschrift fur Immunitatsforschung, Allergie und klinische Immunologie 140:259-267.