Laboratory of Nucleic Acid Vaccines
Shan Lu, M.D., Ph.D.
Associate Professor of
Our main interest is to understand the immunogenicity of protein antigens. The human immunodeficiency virus type-1 (HIV-1) envelope proteins (Env) is used as a model system in our lab. Env, a two-subunit protein, is generated during the posttranslational cleavage process from a single precursor polyprotein. Env heterodimers are further organized into an oligomeric complex. Env conformation is critical for the interaction of HIV-1 with a number of viral receptors. Our work is to understand the immunogenicity of various Env subunits from different HIV-1 strains and to find the Env structures that HIV-1 uses to escape from host immune surveillance. Such information will be used to design noval HIV-1 vaccines. Direct DNA immunization using eukaryotic expression vectors to make proteins in vivo is a unique approach we have been using to study the immunogenicity of protein antigens. We are also working to further improve this evolving technology by studying the roles of cytokines and adjuvants in inducing the desired immune responses by direct DNA immunization.
Lu, S., Reyes, V.E., Bositis, C.M., Goldschmidt, T.G., Lam, V., Torgerson, R.R., Ciardelli, T., Hardy, L., Lew, R.A. and Humphreys, R.E. Biophysical mechanism of the scavenger site near T cell-presented epitopes. 1992. Vaccine, Vol.10, No.1, 3-7.
Lu, S. and Robinson, H. HIV-1-NL4-3 entry into T-cells: more rapid escape from an anti-V3 loop than anti-receptor antibody. 1992. Journal of Virology. Vol. 66, No. 4, 2547-2550.
Lu, S., Santoro, J., Johnson, E., Fuller, D., Haynes, J. and Robinson, H. Use of DNAs expressing HIV-1 Env and noninfectious HIV-1 particles to raise antibody responses in mice. 1995. Virology. Vol. 209, 147-154.
Yasutomi, Y., Robioson, H.L., Lu, S., Mustafa, F., Lekutis, C., Arthos, J., Mullins, J., Voss, G., Manson, K., Wyand, M. and Letvin, N.L.. Simian immunodeficiency virus-specific cytotoxic T lymphocyte induction through DNA vaccination of rhesus monkeys. 1996. Journal of Virology. Vol. 70, 678-681.
Lu, S., Arthos, J., Montefiori, D., Yasutomi, Y., Manson, K., Mustafa, F., Johnson, E., Santoro, J.C., Wissink, J., Mullins, J.I., Haynes, J.R., Letvin, N.L., Wyand, M. and Robioson, H.L. Simian Immunodeficiency Virus DNA Vaccine Trial in Macaques. Journal of
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