Evaluation of the anti-tuberculosis activity generated by different multigene DNA vaccine constructs

Michela Sali, Sandra Clarizio, Cinzia Pusceddu, Antonella Zumbo, Giovanni Pecorini, Stefano Rocca, Stefania Zanetti, Giovanni Delogu, Giovanni Fadda

Research output: Contribution to journalArticlepeer-review

Abstract

Development of multigenic constructs expressing Mycobacterium tuberculosis (Mtb) antigens may be a strategy to obtain improved DNA vaccines against tuberculosis (TB). Several multigenic constructs expressing two or three Mtb antigens as fusion proteins were developed, both as tPA- and ubiquitin-fusion proteins. To demonstrate proper protein expression and intracellular turnover all multiantigens were tagged with the HA epitope and constructs were used to transfect rhabdomyosarcoma (RD) cells. Antigen expression was demonstrated by immunofluorescence using anti-HA antibodies. C57Bl/6 mice were immunized with selected constructs and protective activity was assessed following aerogenic challenge with Mtb. Several of these constructs induced a significant level of protection in the lung and in the spleen. Immunization with the construct expressing tPA85B-ES6 induced a level of protection that approached that provided by BCG. Immunization with a combination of these constructs induced levels of protection that were not superior to those elicited by a single combination, and immunization with a construct expressing five Mtb antigens could not provide an improved level of protection compared to tPA85B-ES6. We conclude that the activity of a DNA vaccine based on tPA85B-ES6 cannot be enhanced by broadening the antigen repertoire with other highly immunogenic secreted Mtb proteins.

Original languageEnglish
Pages (from-to)605-612
Number of pages8
JournalMicrobes and Infection
Volume10
Issue number6
DOIs
Publication statusPublished - May 2008

Keywords

  • DNA vaccines
  • Mycobacterium
  • Tuberculosis

ASJC Scopus subject areas

  • Microbiology
  • Infectious Diseases

Fingerprint Dive into the research topics of 'Evaluation of the anti-tuberculosis activity generated by different multigene DNA vaccine constructs'. Together they form a unique fingerprint.

Cite this