The comparative efficacy of CTLA-4 and L-selectin targeted DNA vaccines in mice and sheep
- Author(s)
- Drew, DR; Boyle, JS; Lew, AM; Lightowlers, MW; Chaplin, PJ; Strugnell, RA;
- 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
- Publisher's Version
- https://doi.org/10.1016/S0264-410X(01)00196-7
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2001-08-14 12:00:00