Mucosal immunization with DNA-liposome complexes.
The mucosal surfaces represent the primary site for transmission of several viruses including HIV. To prevent mucosal transmission and dissemination to the regional lymph nodes, an effective HIV vaccine may need to stimulate immune responses at the genital and rectal mucosa. Optimal induction of mucosal immunity in general requires targeting antigens to the specialized antigen presenting cells of mucosal associated lymphoid tissues. The nasal mucosa may provide a simple, non-invasive route to deliver DNA encoding the introduced gene to stimulate mucosal immunity. As a first step to evaluate the feasibility of this approach, we have investigated as a model system, systemic and mucosal immune responses elicited to firefly luciferase generated by DNA immunization. Incorporating DNA into liposomes with cationic lipids enhanced luciferase expression in nasal tissue, and was associated with induction of a humoral response in serum and vaginal fluids and also a proliferative and cytotoxic T lymphocyte response in the spleen and iliac lymph nodes draining the genital and rectal mucosa.
Klavinskis
L S
LS
Department of Immunology, Guy's Hospital Medical School, United Medical School of Guy's Hospital, London, UK.
Gao
L
L
Barnfield
C
C
Lehner
T
T
Parker
S
S
D016915:AIDS Vaccines / Q000008:administration & dosage* / Q000276:immunology; D000281:Administration, Intranasal; D000818:Animals; D004279:DNA, Viral / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015483:HIV Antibodies / Q000096:biosynthesis*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D018928:Immunity, Mucosal; D008055:Lipids; D008081:Liposomes; D051379:Mice; D010714:Phosphatidylethanolamines; D000644:Quaternary Ammonium Compounds; D013601:T-Lymphocytes / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000276:immunology
D016915:AIDS Vaccines; D004279:DNA, Viral; D015483:HIV Antibodies; D008055:Lipids; D008081:Liposomes; D010714:Phosphatidylethanolamines; D000644:Quaternary Ammonium Compounds; D019444:Vaccines, DNA; C087276:(3-dimyristyloxypropyl)(dimethyl)(hydroxyethyl)ammonium; C020888:1,2-dielaidoylphosphatidylethanolamine