title: DNA-based HIV vaccines do not induce generalized activation in mucosal tissue T cells.
abstract: HIV preferentially infects activated T cells, and activated mucosal CD4+ T cells are the primary sites of viral replication. One potential explanation for increased HIV acquisition rates in the STEP study is that vaccination with adenoviral (Ad) vectors increased CD4+ T cell activation levels at the site of infection, a concept that others and we continue to explore. Whether vaccination with HIV vaccine platforms increases the activation state of CD4+ T cells within peripheral tissues, such as the gastro-intestinal (GI) mucosa, is exceptionally important to determine as a vaccine safety measure, given the susceptibility of activated CD4+ T cells to HIV infection. In this study we examined whether vaccination with DNA plasmids and chemokine adjuvants alter the activation state of T cells within the GI mucosa, inguinal LN, and peripheral blood. T cell activation state was measured by expression of CD25, CD69, and HLA-DR over the course of the prime/boost study. DNA plasmid vaccination did not increase expression of any of these markers in the 3 tissues studied. Addition of the gut-homing chemokine TECK during DNA plasmid vaccination did not alter activation levels of CD4+ T cells at any of these sites. These findings indicate that DNA vaccines do not elicit generalized mucosal T cell activation. Thus, DNA platforms may be especially suitable for HIV vaccine development, where bystander activation could promote increased HIV transmission.
authors.affiliation: Department of Microbiology; Perelman School of Medicine; University of Pennsylvania; Philadelphia, PA USA.
authors.forename: Morgan A
authors.initials: MA
authors.lastname: Reuter
authors.forename: Sally
authors.initials: S
authors.lastname: Yuan
authors.forename: Preston A
authors.initials: PA
authors.lastname: Marx
authors.forename: Michele A
authors.initials: MA
authors.lastname: Kutzler
authors.forename: David B
authors.initials: DB
authors.lastname: Weiner
authors.forename: Michael R
authors.initials: MR
authors.lastname: Betts
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D008213:Lymphocyte Activation / Q000276:immunology; D008253:Macaca mulatta; D009092:Mucous Membrane / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D019444:Vaccines, DNA
keywords: DNA vaccine; HIV; T cell; activation; mucosal tissue