A fusion DNA vaccine that targets antigen-presenting cells increases protection from viral challenge

Deliyannis, G; Boyle, JS; Brady, JL; Brown, LE; Lew, AM

Author(s): Deliyannis, G; Boyle, JS; Brady, JL; Brown, LE; Lew, AM;
Details: Publication Year 2000-06-06,Volume 97,Issue #12,Page 6676-6680
Journal Title: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Publication Type: Journal Article
Abstract: Improving the immunological potency, particularly the Ab response, is a serious hurdle for the protective efficacy and hence broad application of DNA vaccines. We examined the immunogenicity and protective efficacy of a hemagglutinin-based influenza DNA vaccine that was targeted to antigen-presenting cells (APCs) by fusion to CTLA4, The targeted vaccine was shown to induce an accelerated and increased Ab response (as compared with those receiving the nontargeted control) that was predominated by IgG1 and recognized conformationally dependent viral epitopes, Moreover, mice receiving the APC-targeted DNA vaccine had significantly reduced viral titers (100-fold) after a nonlethal virus challenge. The increased protective efficacy was most likely because of increased Ab responses, as cytotoxic T lymphocyte responses were not enhanced. Targeting was demonstrated by direct binding studies of CTLA4 fusion proteins to the cognate ligand (B7; expressed on APCs in vivo). In addition, a targeted protein was detected at 4-fold higher levels in draining lymph nodes within 2-24 h of administration. Therefore, this study demonstrates that targeting DNA-encoded antigen to APCs results in enhanced immunity and strongly suggests that this approach may be useful in improving the protective efficacy of DNA vaccines.
Publisher: NATL ACAD SCIENCES
Keywords: CYTOTOXIC T-LYMPHOCYTES; INFLUENZA-VIRUS; IMMUNE-RESPONSE; PLASMID DNA; IMMUNIZATION; INDUCTION; HEMAGGLUTININ; INFECTION; ANTIBODY; ROUTE
Publisher's Version: https://doi.org/10.1073/pnas.120162497
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2000-06-06 12:00:00