Department Affiliation: Primary: Pharmacology and Molecular Sciences; Secondary: Oncology,
Johns Hopkins Singapore
Degree: M.D., Stanford University
Rank: Professor
Telephone Number : 410-955-8484
Fax Number: 410-955-1894
E-mail address: taugust@jhmi.edu
School of Medicine Address: 311 Biophysics Building, 725 N. Wolfe St., Baltimore, MD 21205
Genetic immunotherapy of infectious diseases and cancer by targeting DNA encoded antigen chimeras to MHC II; MHC II antigen presentation; development of DNA vaccines; immune tolerance
The research of this laboratory is directed at programs for genetic immunotherapy and studies of the mechanisms of MHC II antigen presentation and immune tolerance, and is also being conducted in laboratories of The Johns Hopkins Singapore Biomedical Centre. Current programs include studies in mice, monkeys and humans.
- A novel strategy for genetic immunotherapy by antigen targeting to helper T cells - We have developed a strategy for targeting the protein products of DNA vaccines to the major histocompatability complex (MHC) class II pathway for antigen presentation to CD4+ helper T cells. The DNA vaccine is constructed as a recombinant gene chimera, containing the antigen sequence attached to the the LAMP lysosomal membrane protein that is co-localized with MHC II of antigen presenting cells. Studies with mice and monkeys have shown that the targeted antigen induces markedly enhanced immune responses, antibody, CD4 and CD8, as compared to the nontargeted antigen. Studies are currently in progress with DNA vaccines to several viruses, HIV-1, flaviviruses, and SARS CoV are leading projects, and the BCR/Abl cancer antigen of chronic myelogenous leukemia. Other infectious disease agents and putative cancer antigens are also possible targets of this application.
- Alternative pathways for targeting of DNA encoded antigens to the MHC II pathway for antigen processing and presentation - In addition to utilizing LAMP/antigen chimeras, we are investigating the application of other systems that traffick to MHC II, including the dendritic cell receptors that capture extracellular antigens for endocytosis to the MHC II compartment. Additional LAMP molecules, including DC-LAMP, a specialized member of the LAMP family of proteins that is unique to dendritic cells and is co-expressed with MHC II, are also being investigated.
- Immune response mechanisms: These studies also encompass a variety of immune response mechanisms that individually are being analyzed: formation of immunological memory; e.g., immunodiagnosis by analysis of recall memory T- and B-cells responses, antigen-specific immunomodulation; antigen epitope identification and epitope-based vaccines.
Representative Publications:
- Valentin A, Chikhlikar P, Patel V, Rosati M, Maciel M, Chang KH, Silvera P, Felber BK, Pavlakis GN, August JT, Marques ET (2009) Comparison of DNA vaccines producing HIV-1 gag and LAMP/gag chimera in rhesus macaques reveals antigen-specific T-cell responses with distinct phenotypes. Vaccine 27(35):4840-9. Pub Med Reference
- Koo QY, Khan AM, Jung KO, Ramdas S, Miotto O, Tan TW, Brusic V, Salmon J, August JT (2009) Conservation and variability of West Nile virus proteins. PLoS One. 4 (4), e5352. Pub Med Reference
- Khan AM, Miotto O, Nascimento EJ, Srinivasan KN, Heiny AT, Zhang GL, Marques ET, Tan TW, Brusic V, Salmon J, August JT (2008) Conservation and variability of dengue virus proteins: implications for vaccine design. PLoS Negl Trop Dis. 2 (8), e272. Pub Med Reference
- Rosati M, Valentin A, Jalah R, Patel V, von Gegerfelt A, Bergamaschi C, Alicea C, Weiss D, Treece J, Pal R, Markham PD, Marques ET, August JT, Khan A, Draghia-Akli R, Felber BK, Pavlakis GN (2008) Increased immune responses in rhesus macaques by DNA vaccination combined with electroporation. Vaccine. 26(40):5223-9. Pub Med Reference
- Miotto O, Heiny A, Tan TW, August JT, Brusic V (2008) Identification of human-to-human transmissibility factors in PB2 proteins of influenza A by large-scale mutual information analysis. BMC Bioinformatics. 9 Suppl 1, S18. PubMed Reference
- Heiny AT, Miotto O, Srinivasan KN, Khan AM, Zhang GL, Brusic V, Tan TW, August JT (2007) Evolutionarily conserved protein sequences of influenza a viruses, avian and human, as vaccine targets. PLoS ONE. 2 (11), e1190. Pub Med Reference
- Khan AM, Miotto O, Heiny AT, Salmon J, Srinivasan KN, Nascimento EJ, Marques ET, Brusic V, Tan TW, August JT (2006) A systematic bioinformatics approach for selection of epitope-based vaccine targets. Cell Immunol. 244 (2), 141-7. Pub Med Reference
- Khan AM, Heiny AT, Lee KX, Srinivasan KN, Tan TW, August JT, Brusic V (2006) Large-scale analysis of antigenic diversity of T-cell epitopes in dengue virus. BMC Bioinformatics. 7 Suppl 5, S4. Pub Med Reference
- Chikhlikar P, de Arruda LB, Maciel M, Silvera P, Lewis MG, August JT, Marques ET (2006) DNA encoding an HIV-1 Gag/human lysosome-associated membrane protein-1 chimera elicits a broad cellular and humoral immune response in Rhesus macaques. PLoS ONE. 1, e135. Pub Med Reference
- Arruda LB, Sim D, Chikhlikar PR, Maciel M, Akasaki K, August JT, Marques ET (2006) Dendritic cell-lysosomal-associated membrane protein (LAMP) and LAMP-1-HIV-1 gag chimeras have distinct cellular trafficking pathways and prime T and B cell responses to a diverse repertoire of epitopes. J Immunol. 177 (4), 2265-75. Pub Med Reference
- Valentin A, Chikhlikar P, Patel V, Rosati M, Maciel M, Chang KH, Silvera P, Felber BK, Pavlakis GN, August JT, Marques ET (2009) Comparison of DNA vaccines producing HIV-1 gag and LAMP/gag chimera in rhesus macaques reveals antigen-specific T-cell responses with distinct phenotypes. Vaccine 27(35):4840-9. Pub Med Reference
- Koo QY, Khan AM, Jung KO, Ramdas S, Miotto O, Tan TW, Brusic V, Salmon J, August JT (2009) Conservation and variability of West Nile virus proteins. PLoS One. 4 (4), e5352. Pub Med Reference
- Khan AM, Miotto O, Nascimento EJ, Srinivasan KN, Heiny AT, Zhang GL, Marques ET, Tan TW, Brusic V, Salmon J, August JT (2008) Conservation and variability of dengue virus proteins: implications for vaccine design. PLoS Negl Trop Dis. 2 (8), e272. Pub Med Reference
- Rosati M, Valentin A, Jalah R, Patel V, von Gegerfelt A, Bergamaschi C, Alicea C, Weiss D, Treece J, Pal R, Markham PD, Marques ET, August JT, Khan A, Draghia-Akli R, Felber BK, Pavlakis GN (2008) Increased immune responses in rhesus macaques by DNA vaccination combined with electroporation. Vaccine. 26(40):5223-9. Pub Med Reference
- Miotto O, Heiny A, Tan TW, August JT, Brusic V (2008) Identification of human-to-human transmissibility factors in PB2 proteins of influenza A by large-scale mutual information analysis. BMC Bioinformatics. 9 Suppl 1, S18. PubMed Reference
- Heiny AT, Miotto O, Srinivasan KN, Khan AM, Zhang GL, Brusic V, Tan TW, August JT (2007) Evolutionarily conserved protein sequences of influenza a viruses, avian and human, as vaccine targets. PLoS ONE. 2 (11), e1190. Pub Med Reference
- Khan AM, Miotto O, Heiny AT, Salmon J, Srinivasan KN, Nascimento EJ, Marques ET, Brusic V, Tan TW, August JT (2006) A systematic bioinformatics approach for selection of epitope-based vaccine targets. Cell Immunol. 244 (2), 141-7. Pub Med Reference
- Khan AM, Heiny AT, Lee KX, Srinivasan KN, Tan TW, August JT, Brusic V (2006) Large-scale analysis of antigenic diversity of T-cell epitopes in dengue virus. BMC Bioinformatics. 7 Suppl 5, S4. Pub Med Reference
- Chikhlikar P, de Arruda LB, Maciel M, Silvera P, Lewis MG, August JT, Marques ET (2006) DNA encoding an HIV-1 Gag/human lysosome-associated membrane protein-1 chimera elicits a broad cellular and humoral immune response in Rhesus macaques. PLoS ONE. 1, e135. Pub Med Reference
- Arruda LB, Sim D, Chikhlikar PR, Maciel M, Akasaki K, August JT, Marques ET (2006) Dendritic cell-lysosomal-associated membrane protein (LAMP) and LAMP-1-HIV-1 gag chimeras have distinct cellular trafficking pathways and prime T and B cell responses to a diverse repertoire of epitopes. J Immunol. 177 (4), 2265-75. Pub Med Reference
Other graduate programs in which Dr. August participates:
