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The major focus of my laboratory is AIDS-related research, including examination of mechanisms of protective immunity induced by SIV vaccines, analysis of AIDS immunopathogenesis, and the development of new immune-based therapeutic strategies for AIDS. Current projects in my laboratory include:
Immune responses responsible for protection of macaques immunized with live attenuated SIV vaccines. Analysis of protective immunity in macaques immunized with live attenuated SIV strains, one of the most effective vaccine approaches in primates, represents one of the leading experimental models in which to study protective immunity against primate lentiviruses. Prior publications from our laboratory have demonstrated that live attenuated SIV vaccines are able to induce vigorous and durable cellular immune responses and to protect against mucosal challenge. Ongoing research is focused on the use of in vivo lymphocyte depletion studies, and the application of multicolor flow cytometric techniques and microarray analysis to provide new insights into adaptive and innate immune responses induced by live attenuated SIV strains.
Virus-specific CD4+ T cell responses in AIDS pathogenesis. Recent work by our laboratory has identified a novel subpopulation of SIV-specific CD4+ T cells with direct effector function in macaques infected with SIVdeltanef, a previously unrecognized immune response that may play a role in protective immunity induced by live attenuated SIV. Current research is focused on correlating this response with the onset of protective immunity and analyzing the ability of these cells to inhibit viral replication.
Genetic therapies for AIDS in the SIV-macaque model. Previous work by our group has demonstrated that transduction of CD34+ hematopoietic cells with genes that inhibit SIV replication can protect T cell and macrophage progeny from SIV infection. Ongoing work is analyzing the efficacy of antisense and shRNA-based mechanisms to interfere with viral replication and analyzing various strategies to increase the efficiency of genetically-modified hematopoietic cells in macaques that have received infusions of transduced hematopoietic stem cells.
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References:
Gauduin M-C, Glickman RL, Ahmad S, Yilma T, Johnson RP. Immunization with live attenuated simian immunodeficiency virus induces strong type 1 T helper responses and beta-chemokine production. Proc. Nat. Acad. Sci. USA 1999; 96:14,031-14,036.
Cromwell MA, Veazey RS, Altman JD, Mansfield KG, Glickman R, Allen TM, Watkins DI, Lackner AA, Johnson RP. Induction of mucosal homing virus-specific CD8+ T lymphocytes by attenuated simian immunodeficiency virus. J. Virol. 2000; 74:8762-8766.
Abdel-Motal UM, Gillis J, Manson K, Wyand M, Montefiori D, Stefano-Cole K, Montelaro RC, Altman JD, Johnson RP. Kinetics of expansion of SIV Gag-specific CD8+ T lymphocytes following challenge of vaccinated macaques. Virology 2005; 333:226-238.
Macchia I, Gauduin M-C, Kaur A, Johnson RP. Expression of CD8alpha identifies a distinct subset of effector memory CD4+ T lymphocytes. Immunology 2006; 119:232-242.
Gauduin M-C, Yu Y, Barabasz A, Carville A, Piatak M, Lifson JD, Desrosiers RC, Johnson RP. Induction of a virus-specific effector memory CD4+ T cell response by attenuated SIV infection. J. Exp. Med. 2006; 203:2661-2672.
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