August Lab

Thomas August's laboratory at the Department of Pharmacology & Molecular Sciences is currently engaged in research involving Lysosome-Associated Membrane Protein (LAMP), Dengue Fever, Epitopes Discovery, and HIV with an emphasis on novel vaccine development strategies.

Current Research

Epitope based vaccine design, epitope expression, processing, presentation and immune function in HLA-transgenic mice, and ex vivo dengue vaccine activation of human memory B and T cells

The August lab is engaged in the design and validation of epitope-based vaccines conducted at the level of the antigen presenting cell, with both in vivo HLA transgenic animal and ex vivo human experimental protocols. The vaccine system developed in the lab is unique in that the vaccine is constructed as a chimera of the antigen and the lysosome-associated membrane protein (LAMP). LAMP-mediated trafficking of the antigen to the MHC processing compartment of antigen presenting cells has been shown in many studies to enhance the immunogenicity of the protein, presumably by increasing antigen epitope presentation to CD4 helper T cells. This vaccine chimera applied to HIV-1 Gag antigen has been shown to be highly effective in monkey immunization and is now in an NIAID developmental program for human clinical studies under grant R37AI41908 (Marques et al, 2003).

A dengue virus vaccine development program is also underway, involving collaboration with the Institute of Infocomm Research, Singapore, and the Aggeu Magalhães Research Center and FIOCRUZ, Recife, Brazil under the auspices of an NIAID grant (1 U19 AI56541).

Representative Publications

1: Marques ET Jr, Chikhlikar P, de Arruda LB, Leao IC, Lu Y, Wong J, Chen JS, Byrne B, August JT. HIV-1 p55Gag encoded in the lysosome-associated membrane protein-1 as a DNA plasmid vaccine chimera is highly expressed, traffics to the major histocompatibility class II compartment, and elicits enhanced immune responses. J Biol Chem. 2003 Sep 26;278(39):37926-36. Epub 2003 Jun 24. PMID: 12824194

2: Lu Y, Raviprakash K, Leao IC, Chikhlikar PR, Ewing D, Anwar A, Chougnet C, Murphy G, Hayes CG, August TJ, Marques ET Jr. Dengue 2 PreM-E/LAMP chimera targeted to the MHC class II compartment elicits long-lasting neutralizing antibodies. Vaccine. 2003 May 16;21(17-18):2178-89. PMID: 12706709

3: Rowell JF, Ruff AL, Guarnieri FG, Staveley-O'Carroll K, Lin X, Tang J, August JT, Siliciano RF. Lysosome-associated membrane protein-1-mediated targeting of the HIV-1 envelope protein to an endosomal/lysosomal compartment enhances its presentation to MHC class II-restricted T cells. J Immunol. 1995 Aug 15;155(4):1818-28. PMID: 7636236

4: Ruff AL, Guarnieri FG, Staveley-O'Carroll K, Siliciano RF, August JT. The enhanced immune response to the HIV gp160/LAMP chimeric gene product targeted to the lysosome membrane protein trafficking pathway. J Biol Chem. 1997 Mar 28;272(13):8671-8. PMID: 9079699