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Michael M. Corb, Ph.D.
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Professor
E1252 BSTWR
200 Lothrop Street
Pittsburgh, Pennsylvania 15261
Phone: (412) 648-9462
Fax: (412) 648-1448
E-mail: mcorb@pitt.edu
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Research
We are currently experiencing an epidemic of AIDS of global proportions, with some countries in Southern Africa experiencing an HIV infection rate as high as 25%. The acute viruses smallpox and poliovirus have taught us that the only truly effective countermeasure against an epidemic of this proportion is a vaccine effective in prevention. Although we have learned much about immune responses that exert control of virus replication, an HIV vaccine that can prevent infection has proven elusive.
HIV is also problematic because infection is chronic, persisting until the death of the infected individual. Although antiviral therapy has been shown to be highly effective in prolonging the life of HIV+ patients, an infected population now exists that reaches into the millions worldwide. Our efforts to develop a prophylactive vaccine have shown that robust virus-specific immunity may also be used as an effective therapeutic, particularly if it can be co-administered with effective antiretroviral drugs (ART). Using the SIV:macaque model for AIDS developed in my laboratory, we have been studying the ability of a gene gun delivered DNA vaccine expressing SIV gag/pol/env with and without the potent genetic adjuvant E. coli enterotoxin (LT) as an adjunct to ART to suppress virus burden during ART and to prevent virus rebound after ART is discontinued. Prevention of viral rebound after discontinuation of ART is particularly important because long term ART is toxic, expensive, and eventually gives rise to drug resistant strains. In collaboration with GlaxoSmithKline and Powdermed Vaccines (now owned by Pfizer), we have demonstrated that immunization of SIV infected macaques with SIV gag/pol/env + LT, but not SIV gag/pol/env alone, significantly reduces viral rebound after ART is discontinued. Such studies are paving the way for similar trials in HIV+ humans.
These studies are also enabling us to determine where virus replication persists during ART so that we may target vaccines to these sites. Serial collections of the gut associated tissues were performed by our research veterinarians during and post ART therapy for analysis. Preliminary evidence suggests that primary sites for continued virus replication during ART are mesenteric lymph nodes and jejunal lamina propria, but not peripheral mononuclear cells and surface lymph nodes. Molecular characterization of these viruses to determine how they can evade both immune and ART therapy is underway.
My basic interest in the use of primate models for infectious disease research have also resulted in a new grant award to develop a DNA vaccine for pandemic influenza. These studies will enable the development of aerosol models for highly pathogenic influenza in both ferrets and rhesus macaques, provide infected animals with which to explore the basic mechanisms of pathogenesis, and develop the model with which to test mucosal vaccines.
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Selected Publications
- Bissel SJ, Wang G, Bonneh-Barkay D, Starkey A, Trichel AM, Murphey-Corb M, Wiley CA. 2008. "Systemic and brain macrophage infection in Simian Immunodeficiency Virus Encephalitis" J Virol. 82:5031-42 | Abstract
- Fallert BA, Poveda S, Schaefer TM, Pfeifer ME, Sanghavi SK, Watkins SC, Murphey-Corb MA, Tarwater PM, Kirschner DE, Reinhart TA. 2008. "Virologic and immunologic events in hilar lymph nodes during simian immunodeficiency virus infection: development of polarized inflammation" J Acquir Immune Defic Syndr 47:16-26 | Abstract
- Bonneh-Barkay D, Bissel SJ, Wang G, Fish KN, Nicholl GC, Darko SW, Medina-Flores R, Murphey-Corb M, Rajakumar PA, Nyaundi J, Mellors JW, Bowser R, Wiley CA. 2008. "YKL-40, a marker of simian immunodeficiency virus encephalitis, modulates the biological activity of basic fibroblast growth factor" Am J Pathol. 173:130-43. | Abstract
- Taber R, Rajakumar PA, Fuller DH, Trichel AM, Dowling P, Meleason D, Amedee A, Murphey-Corb M. 2006. "Effects of monotherapy with (R)-9-(2-phosphonylmethoxypropyl)adenine (PMPA) on the evolution of a primary Simian immunodeficiency virus (SIV) isolate" Virology 354:116-31. | Abstract
- Steckbeck JD, Grieser HJ, Sturgeon T, Taber R, Chow A, Bruno J, Murphy-Corb M, Montelaro RC, Cole KS. 2006. "Dynamic evolution of antibody populations in a rhesus macaque infected with attenuated simian immunodeficiency virus identified by surface plasmon resonance" J Med Primatol. 35:248-60 | Abstract
- Bissel SJ, Wang G, Trichel AM, Murphey-Corb M, Wiley CA. 2006. "Longitudinal analysis of monocyte/macrophage infection in simian immuno-deficiency virus-infected, CD8+ T-cell-depleted macaques that develop lentiviral encephalitis. Am J Pathol. 168:1553-69. | Abstract
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