Super-activated interferon-regulatory factors can enhance plasmid immunization.
We have been investigating the adjuvant properties of two super-activated interferon-regulatory factors (IRFs), IRF-3(5D) and IRF7/3A, identified in our previous studies of structure-function relationships, for enhancing plasmid vaccines. Intramuscular injection of plasmid cocktails encoding IRF-3(5D) and IRF7/3A molecules elicited cytotoxic T cell responses in over 80% of mice following a single immunization compared to a 20% response-rate using a control cocktail. Most interestingly, greater than 60% of mice immunized with the super-activated IRFs developed antigen-specific antibodies compared to 0% of the mice in the control group. Finally, vaccines which incorporated the super-activated IRFs provided greater protection against challenge with a recombinant vaccinia virus. These results support further investigation of the potential of these agents as adjuvants for genetic immunization.
Bramson
Jonathan L
JL
Department of Pathology and Molecular Medicine, Center for Gene Therapeutics, McMaster University, 1200 Main Street West, Hamilton, Ont., Canada L8N 3Z5. bramsonj@mcmaster.ca
Dayball
Kelley
K
Hall
Jennifer R
JR
Millar
James B
JB
Miller
Mark
M
Wan
Yong Hong
YH
Lin
Rongtuan
R
Hiscott
John
J
D000818:Animals; D000917:Antibody Formation; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D022761:Gene Transfer, Horizontal; D050838:Interferon Regulatory Factor-3; D050839:Interferon Regulatory Factor-7; D051379:Mice; D008810:Mice, Inbred C57BL; D010957:Plasmids / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014157:Transcription Factors / Q000235:genetics*; D014611:Vaccination; D019444:Vaccines, DNA / Q000276:immunology*
D004268:DNA-Binding Proteins; D050838:Interferon Regulatory Factor-3; D050839:Interferon Regulatory Factor-7; C494233:Irf3 protein, mouse; C494235:Irf7 protein, mouse; D014157:Transcription Factors; D019444:Vaccines, DNA