Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Vaccine. 2014 Apr 17;32(19):2173-80. doi: 10.1016/j.vaccine.2014.02.056. Epub 2014 Mar 11.

As a genetic adjuvant, CTA improves the immunogenicity of DNA vaccines in an ADP-ribosyltransferase activity- and IL-6-dependent manner.

Author information

  • 1Shanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Key Laboratory of Medical Molecular Virology of Ministry of Education/Health, Shanghai Medical College, Fudan University, Shanghai 201508, China.
  • 2Shanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Key Laboratory of Medical Molecular Virology of Ministry of Education/Health, Shanghai Medical College, Fudan University, Shanghai 201508, China; Institute of Biomedical Science, Fudan University, Shanghai 200032, China.
  • 3Shanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Key Laboratory of Medical Molecular Virology of Ministry of Education/Health, Shanghai Medical College, Fudan University, Shanghai 201508, China; Institute of Biomedical Science, Fudan University, Shanghai 200032, China. Electronic address: jianqingxu2008@gmail.com.

Abstract

Cholera toxin (CT) and its subunits (A and B) have been intensively investigated as adjuvants for protein-based vaccines. Their underlying mechanisms vary with respect to the inoculation route used. By fusing the CTA gene to either the HIV-1-derived Tat-Rev-Vif-Integrase-Nef fusion gene or the OVA gene, our study showed that the fusion of CTA in these DNA vaccines had no cytotoxic effect in vitro and significantly improved both the quantity and quality of the elicited CD8(+) T cell responses. Further experiments identified that the fusion of CTA in these DNA vaccines augmented the secretion of IL-6 in a manner that was dependent on its ADP-ribosyltransferase activity, and protein kinase A (PKA) was found to be the major mediator of its downstream signaling. By site-directed mutagenesis of the ADP-ribosyltransferase catalytic center and in vivo RNAi, we demonstrated that the ADP-ribosyltransferase activity and the upregulation of IL-6 were required for the CTA gene-mediated adjuvant effect. These findings demonstrate that when fused to an immunogen gene, the CTA gene could serve as a potent genetic adjuvant, providing new insights into the mechanisms of CTA as an adjuvant.

Copyright © 2014 Elsevier Ltd. All rights reserved.

KEYWORDS:

Adjuvant; Cholera toxin A; DNA vaccine; IL-6; T cell immunity

PMID:
24631089
[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Write to the Help Desk