Treatment of HIV-infected patients with highly active anti-retroviral therapy (HAART) regimens has led to marked reductions in HIV-1 viral load and improvements in peripheral CD4+ T cell counts. However, there is evidence that HAART alone may not result in complete return of normal lymphocyte number and function, and, in particular, HIV-specific immune function. We hypothesize that therapeutic immunization with autologous cultured DC, appropriately loaded with HIV antigens, will lead to the generation of a more effective cellular immune response to HIV-1 in the setting of effective anti-retroviral therapy. We propose to investigate the possibility that DC derived from HIV-infected patients on HAART have the potential to stimulate a strong, coordinate (CTL and Th) HIV-specific cellular response in vitro. This in vitro model will allow us to determine the feasibility of reconstituting HIV-specific immunity using DC administration following effective anti-retroviral therapy.
In Aim 1 we will deliver HIV antigens to autologous cultured DC in order to stimulate and maintain HIV-specific T cell responses.
In Aim 2 we will evaluate the impact of cytokines known to promote cell-mediated immunity on the magnitude and diversity of the antigen-specific T cell responses generated in vitro using antigen-primed DC.
In Aim 3, we will investigate the effects of DC-T cell interactions on HIV-1 replication in vitro, and the role that cytokines play in regulating HIV replication in this setting.
In Aim 4 we will perform clinical protocols to evaluate the safety and immunogenicity of autologous cultured DC, loaded with HIV and recall antigens, and in subsequent trials in combination with cytokines, administered to HIV-infect patients receiving HAART.

Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Pittsburgh
United States
Zip Code
Macatangay, Bernard J C; Riddler, Sharon A; Wheeler, Nicole D et al. (2016) Therapeutic Vaccination With Dendritic Cells Loaded With Autologous HIV Type 1-Infected Apoptotic Cells. J Infect Dis 213:1400-9
Soloff, Adam C; Liu, Xiangdong; Gao, Wentao et al. (2009) Adenovirus 5- and 35-based immunotherapy enhances the strength but not breadth or quality of immunity during chronic SIV infection. Eur J Immunol 39:2437-49
Brown, Kevin N; Trichel, Anita; Barratt-Boyes, Simon M (2007) Parallel loss of myeloid and plasmacytoid dendritic cells from blood and lymphoid tissue in simian AIDS. J Immunol 178:6958-67
Barratt-Boyes, Simon M; Soloff, Adam C; Gao, Wentao et al. (2006) Broad cellular immunity with robust memory responses to simian immunodeficiency virus following serial vaccination with adenovirus 5- and 35-based vectors. J Gen Virol 87:139-49
Gao, Wentao; Rzewski, Alexis; Sun, Huijie et al. (2004) UpGene: Application of a web-based DNA codon optimization algorithm. Biotechnol Prog 20:443-8
Barron, Michelle A; Blyveis, Naomi; Palmer, Brent E et al. (2003) Influence of plasma viremia on defects in number and immunophenotype of blood dendritic cell subsets in human immunodeficiency virus 1-infected individuals. J Infect Dis 187:26-37
Riddler, Sharon A; Smit, Ellen; Cole, Stephen R et al. (2003) Impact of HIV infection and HAART on serum lipids in men. JAMA 289:2978-82
Donnenberg, Vera S; Donnenberg, Albert D (2003) Identification, rare-event detection and analysis of dendritic cell subsets in broncho-alveolar lavage fluid and peripheral blood by flow cytometry. Front Biosci 8:s1175-80
Harshyne, Larry A; Zimmer, Michael I; Watkins, Simon C et al. (2003) A role for class A scavenger receptor in dendritic cell nibbling from live cells. J Immunol 170:2302-9
Meidenbauer, Norbert; Hoffmann, Thomas K; Donnenberg, Albert D (2003) Direct visualization of antigen-specific T cells using peptide-MHC-class I tetrameric complexes. Methods 31:160-71

Showing the most recent 10 out of 19 publications