The comparative efficacy of CTLA-4 and L-selectin targeted DNA vaccines in mice and sheep
Details
Publication Year 2001-08-14,Volume 19,Issue #31,Page 4417-4428
Journal Title
VACCINE
Publication Type
Journal Article
Abstract
The access of antigens to antigen presenting cells (APCs) appears to be a rate-limiting step in the generation of immune responses to DNA vaccines. The cytotoxic T lymphocyte antigen 4 (CTLA-4) and L-selectin represent attractive ligands for use in the targeting of antigen to APCs and lymph nodes. CTLA-4 binds with high affinity to the B7 membrane antigen on APCs, while L-selectin functions as a lymphocyte homing marker and binds to CD34 on the surface of high endothelial venule cells. DNA vaccines encoding human immunoglobulin (HIg), fused to either CTLA-4 or L-selectin. have been shown to generate up to 10,000-fold higher anti-HIg antibody responses than DNA vaccines encoding HIg alone. In this study, the ability of CTLA-4 or L-selectin mediated targeting to enhance the humoral immune response to an alternate vaccine antigen was investigated. DNA vaccines encoding CTLA-4-HIg and L-selectin-HIg fused to the host-protective 45W antigen from Taenia oris were constructed. In BALB/c mice. the L-selectin targeted vaccine did not improve either the magnitude or speed of antibody responses of vaccinated mice. In contrast, the CTLA-4 targeted DNA vaccine generated 45W-specific antibody responses which were up to 30-fold higher than those achieved with non-targeted DNA vaccination. The kinetic of the antibody response generated following CTLA-4 targeted DNA vaccination was also significantly faster than that achieved with non-targeted DNA vaccination, or with adjuvanted protein vaccination. Vaccination of outbred sheep with DNA vaccines expressing either murine or ovine CTLA-4 targeted antigen failed to enhance immune responses. These findings indicate that CTLA-4 targeting may find application in the improvement of DNA vaccines, but requires further development for applications in large animal species. (C) 2001 Published by Elsevier Science Ltd.
Publisher
ELSEVIER SCI LTD
Keywords
COLONY-STIMULATING FACTOR; NODE HOMING RECEPTOR; IN-VIVO TRANSFECTION; DIRECT GENE-TRANSFER; DENDRITIC CELLS; IMMUNE-RESPONSES; TAENIA-OVIS; ADHESION MOLECULES; RECOMBINANT ANTIGEN; BINDING
Terms of Use/Rights Notice
Refer to copyright notice on published article.


Creation Date: 2001-08-14 12:00:00
An error has occurred. This application may no longer respond until reloaded. Reload 🗙