I am involved in efforts to elicit a neutralizing immune response against the co-receptor binding domain of HIV-1 gp120. Antibodies to such epitopes are expected to block virus-co-receptor interactions and inhibit infection at the level of virus entry. These antibodies will be useful for passive immunotherapy and as diagnostic reagents. The co-receptor binding domain of gp120 requires conformational changes induced by CD4 binding. Thus we are using covalently crosslinked complexes of gp120 and CD4 to elicit this novel class of co-receptor blocking neutralizing antibodies. In addition, we are examining whether the complexes themselves can be used as subunit or subunit boost vaccines in various adjuvant formulations.
My research efforts continue to focus on the role of chemokines (RANTES, MIP-1 alpha and MIP-1 beta) in the pathogenesis of HIV infection. I am also involved in experiments to determine the value of chemokines in HIV therapy. We are in the process of designing and producing chemokine analogues that may optimize antiviral effects in vivo.
Finnegan, C., Berg, W., Lewis, G.K. and DeVico, A.L. Antigenic Properties of The Human Immunodeficiency Virus Transmembrane Glycoprotein During Cell-Cell Fusion. In press.
Fouts, T., Montefiori, D., Hanson, C., Kalyanaraman, V., DeVico, A. and Pal, R. Broadly Reactive Neutralizing Antibodies Elicited By Crosslinked HIV-1 Envelope-CD4 Receptor Complexes. In press
Finnegan, C., Berg, W., Lewis, G.K. and DeVico, A.L. Temporal Changes In Epitope Exposure on The HIV Envelope During Cell-Cell Fusion. J. Virol. 75: 11096-11105 2001.
Kamin-Lewis R, Abdelwahab SF, Trang C, Baker A, DeVico AL, Gallo RC, Lewis GK. Perforin-Low Memory CD8+ Cells Are the Predominant T Cells In Normal Humans That Synthesize The Beta -Chemokine Macrophage Inflammatory Protein-1beta. Proc Natl Acad Sci U S A 98: 9283-8 2001.
DeVico AL. Mucosal and Systemic HIV Env-Specific CD8(+) T Cells Develop After Intragastric Vaccination with Salmonella Env DNA Vector Vaccine 20: 623-629 2001.
Cocchi, F., DeVico, A.L. et al Higher MIP-1a And MIP-1b Levels From CD8+ T Cells Are Associated With Asymptomatic HIV-1 Infection. Proc Natl Acad Sci U S A. 97:13812-7 2000.
Fouts, T.R., Tuskan, R., Godfrey, K., Reitz, M., Lewis, G.K. and DeVico, A.L. Expression And Characterization Of A Single Chain Polypeptide Analogue Of The HIV-1 Gp120-CD4 Receptor Complex. J. Virol . 74: 11427-11436 2000.
Burns JM, Lewis GK, DeVico AL. 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. Proc Natl Acad Sci U S A. Dec 7;96(25):14499-504. 1999.
Garzino-Demo, A., Moss, R.B., Margolick, J., Cleghorn, F., Sill, A., Blattner, W.A., Cocchi, F., Carlo, D.J., DeVico, A.L., and Gallo, R.C. HIV-inhibitory chemokines in the course of HIV infection. Spontaneous and antigen-induced production of HIV-inhibitory beta-chemokines are associated with AIDS-free status. Proc Natl Acad Sci U S A. 96: 11986-91, 1999.
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