Intralymphatic immunization enhances DNA vaccination.
Although DNA vaccines have been shown to elicit potent immune responses in animal models, initial clinical trials in humans have been disappointing, highlighting a need to optimize their immunogenicity. Naked DNA vaccines are usually administered either i.m. or intradermally. The current study shows that immunization with naked DNA by direct injection into a peripheral lymph node enhances immunogenicity by 100- to 1,000-fold, inducing strong and biologically relevant CD8(+) cytotoxic T lymphocyte responses. Because injection directly into a lymph node is a rapid and easy procedure in humans, these results have important clinical implications for DNA vaccination.
Department of Dermatology, and Institute of Experimental Immunology, Universitätsspital Zürich, Schmelzbergstrasse 12, CH-8091 Zurich, Switzerland. kevin.maloy@path.ox.ac.uk
K J
KJ
Maloy
I
I
Erdmann
V
V
Basch
S
S
Sierro
T A
TA
Kramps
R M
RM
Zinkernagel
S
S
Oehen
T M
TM
Kündig
D000818:Animals; D000956:Antigens, Viral / Q000235:genetics*; D002460:Cell Line; D004279:DNA, Viral / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000235:genetics; D006023:Glycoproteins / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics; D016056:Immunodominant Epitopes / Q000235:genetics; D007272:Injections, Intralymphatic / Q000379:methods; D008216:Lymphocytic Choriomeningitis / Q000517:prevention & control; D008217:Lymphocytic choriomeningitis virus / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010446:Peptide Fragments / Q000235:genetics*; D010957:Plasmids / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014611:Vaccination; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000276:immunology; D014764:Viral Proteins / Q000235:genetics*; D014765:Viral Vaccines / Q000008:administration & dosage* / Q000276:immunology
D000956:Antigens, Viral; D004279:DNA, Viral; D018984:Epitopes, T-Lymphocyte; D006023:Glycoproteins; D018398:Homeodomain Proteins; D016056:Immunodominant Epitopes; D010446:Peptide Fragments; D019444:Vaccines, DNA; D014764:Viral Proteins; D014765:Viral Vaccines; C094244:glycoprotein peptide 33-41, Lymphocytic choriomeningitis virus; C064658:RAG-1 protein