The cellular basis of immune induction at mucosal surfaces by DNA vaccination.
The nasal mucosa provides a simple, non-invasive route to deliver DNA encoding the gene of interest to stimulate mucosal and systemic immune responses. However, unlike the intradermal or intramuscular routes for plasmid DNA (pDNA) delivery, immune responsiveness to antigen exposure at the respiratory mucosa is tightly regulated, consistent with the balance between active immunity and non-responsiveness to pathogenic or inert environmental antigens. We have characterised the antigen presenting cell types, their distribution and activation status following nasal vaccination with pDNA-cytofectin complexes encoding model antigens. We demonstrate that nasal immunisation is associated with expression of the encoded protein in a small population of dendritic cells and macrophages at the site of pDNA delivery, in the draining lymph nodes (LN) and in the spleen. Antigen expression by nasal dendritic cells was associated with up-regulation of surface MHC class II and CD86 expression and functional activation of T-lymphocytes. The results highlight the potential of intranasal vaccination with pDNA, provided the activation / costimulatory requirements for an active immune response are achieved.
Barnfield
C
C
Peter Gorer Department of Immunobiology, Guy's Hospital, GKT, London, UK.
Brew
R
R
Tilling
R
R
Rae
A
A
Wheeler
C
C
Klavinskis
L S
LS
D000281:Administration, Intranasal; D000469:Alkaline Phosphatase / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000818:Animals; D000941:Antigens / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D015870:Gene Expression; D049452:Green Fluorescent Proteins; D018928:Immunity, Mucosal; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009297:Nasal Mucosa / Q000276:immunology; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology
D000941:Antigens; D008164:Luminescent Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D019444:Vaccines, DNA; D049452:Green Fluorescent Proteins; D008156:Luciferases; D000469:Alkaline Phosphatase