title: Dendritic cells primed with a chimeric plasmid containing HIV-1-gag associated with lysosomal-associated protein-1 (LAMP/gag) is a potential therapeutic vaccine against HIV.
abstract: The decline in number and function of T cells is a hallmark of HIV infection, and preservation or restoration of HIV-specific cellular immune response is a major goal of AIDS treatment. Dendritic cells (DCs) play a key role in the initiation and maintenance of the immune response, and their use as a vaccine vehicle is a promising strategy for enhancing vaccine efficacy. We evaluated the potential of DC-mediated immunization with a DNA vaccine consisting of HIV-1-p55gag (gag, group-specific antigen) associated to lysosomal associated protein (LAMP) sequence (LAMP/gag vaccine). Immunization of mice with mouse DCs transfected with LAMP/gag (Lg-mDCs) stimulated more potent B- and T-cell responses than naked DNA or DCs pulsed with inactivated HIV. Anti-Gag antibody levels were sustained for at least 3 mo after immunization, and recall T-cell responses were also strongly detected at this time point. Human DCs transfected with LAMP/gag (Lg-hDCs) were also activated and able to stimulate greater T-cell response than native gag-transfected DCs. Coculture between Lg-hDCs and T lymphocytes obtained from patients with HIV resulted in upregulation of CD38, CD69, HLA-DR, and granzyme B by CD4(+) and CD8(+) T cells, and increased IFN-γ and TNF-α production. These results indicate that the use of LAMP/gag-DC may be an efficient strategy for enhancing immune function in patients with HIV.-Lucas, C. G. D. O., Matassoli, F. L., Peçanha, L. M. T., Santillo, B. T., Oliveira, L. M. D. S., Oshiro, T. M., Marques, E. T. D. A., Jr., Oxenius, A., de Arruda, L. B. Dendritic cells primed with a chimeric plasmid containing HIV-1-gag associated with lysosomal-associated protein-1 (LAMP/gag) is a potential therapeutic vaccine against HIV.
authors.affiliation: Departamento de Virologia, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil;
authors.forename: Carolina G D O
authors.initials: CG
authors.lastname: Lucas
authors.affiliation: Departamento de Virologia, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil;
authors.forename: Flavio L
authors.initials: FL
authors.lastname: Matassoli
authors.affiliation: Departamento de Imunologia, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil;
authors.forename: Ligia M T
authors.initials: LM
authors.lastname: Peçanha
authors.affiliation: Laboratório de Dermatologia e Imunodeficiências (LIM-56), Departamento de Dermatologia, Escola de Medicina, Universidade de São Paulo, São Paulo, Brazil; Institute of Microbiology, Swiss Federal Institute of Technology, Zurich, Switzerland;
authors.forename: Bruna Tereso
authors.initials: BT
authors.lastname: Santillo
authors.affiliation: Laboratório de Dermatologia e Imunodeficiências (LIM-56), Departamento de Dermatologia, Escola de Medicina, Universidade de São Paulo, São Paulo, Brazil;
authors.forename: Luanda Mara da Silva
authors.initials: LM
authors.lastname: Oliveira
authors.affiliation: Laboratório de Dermatologia e Imunodeficiências (LIM-56), Departamento de Dermatologia, Escola de Medicina, Universidade de São Paulo, São Paulo, Brazil;
authors.forename: Telma Miyuki
authors.initials: TM
authors.lastname: Oshiro
authors.affiliation: Department of Infectious Diseases and Microbiology, Center for Vaccine Research, Pittsburgh, Pennsylvania, USA; and Department of Virology, Centro de Pesquisas Aggeu Magalhães (CPqAM), Fundação Oswaldo Cruz (Fiocruz)-Pernambuco, Recife, Brazil.
authors.forename: Ernesto T D A
authors.initials: ET
authors.lastname: Marques
authors.affiliation: Institute of Microbiology, Swiss Federal Institute of Technology, Zurich, Switzerland;
authors.forename: Annette
authors.initials: A
authors.lastname: Oxenius
authors.affiliation: Departamento de Virologia, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; arruda@micro.ufrj.br.
authors.forename: Luciana B
authors.initials: LB
authors.lastname: de Arruda
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D003713:Dendritic Cells; D005260:Female; D015658:HIV Infections / Q000628:therapy*; D006801:Humans; D007156:Immunologic Memory; D052118:Lysosomal-Associated Membrane Protein 1 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids; D011498:Protein Precursors / Q000502:physiology*
chemical_list: D016915:AIDS Vaccines; D052118:Lysosomal-Associated Membrane Protein 1; D011498:Protein Precursors; C059767:p55 gag precursor protein, Human immunodeficiency virus 1
keywords: HIV immunotherapy; T-cell activation; dendritic cell vaccine