title: Generation of antigen-specific immunity following systemic immunization with DNA vaccine encoding CCL25 chemokine immunoadjuvant.
abstract: A significant hurdle in vaccine development for many infectious pathogens is the ability to generate appropriate immune responses at the portal of entry, namely mucosal sites. The development of vaccine approaches resulting in secretory IgA and mucosal cellular immune responses against target pathogens is of great interest and in general, requires live viral infection at mucosal sites. Using HIV-1 and influenza A antigens as models, we report here that a novel systemically administered DNA vaccination strategy utilizing co-delivery of the specific chemokine molecular adjuvant CCL25 (TECK) can produce antigen-specific immune responses at distal sites including the lung and mesenteric lymph nodes in mice. The targeted vaccines induced infiltration of cognate chemokine receptor, CCR9+/CD11c+ immune cells to the site of immunization. Furthermore, data shows enhanced IFN-λ secretion by antigen-specific CD3+/CD8+ and CD3+/CD4+ T cells, as well as elevated HIV-1-specific IgG and IgA responses in secondary lymphoid organs, peripheral blood, and importantly, at mucosal sites. These studies have significance for the development of vaccines and therapeutic strategies requiring mucosal immune responses and represent the first report of the use of plasmid co-delivery of CCL25 as part of the DNA vaccine strategy to boost systemic and mucosal immune responses following intramuscular injection.
authors.affiliation: Department of Microbiology and Immunology; Drexel University College of Medicine; Philadelphia, PA, USA.
authors.forename: Noshin
authors.initials: N
authors.lastname: Kathuria
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Kraynyak
authors.forename: Diane
authors.initials: D
authors.lastname: Carnathan
authors.forename: Michael
authors.initials: M
authors.lastname: Betts
authors.forename: David B
authors.initials: DB
authors.lastname: Weiner
authors.forename: Michele A
authors.initials: MA
authors.lastname: Kutzler
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D019742:Chemokines, CC / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D015497:HIV-1 / Q000276:immunology; D006388:Hemagglutinins / Q000276:immunology; D056724:Immunity, Humoral / Q000276:immunology; D007070:Immunoglobulin A / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids; D013601:T-Lymphocytes / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D019742:Chemokines, CC; D006388:Hemagglutinins; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D019444:Vaccines, DNA; D007371:Interferon-gamma