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

Sali, Michela and Clarizio, Sandra and Pusceddu, Cinzia and Zumbo, Antonella and Pecorini, Giovanni and Rocca, Stefano and Zanetti, Stefania Anna Lucia and Delogu, Giovanni and Fadda, Giovanni (2008) Evaluation of the anti-tuberculosis activity generated by different multigene DNA vaccine constructs. Microbes and Infection, Vol. 10 (6), p. 605-612. ISSN 1286-4579. Article.

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DOI: 10.1016/j.micinf.2008.02.012

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.

Item Type:Article
ID Code:1987
Status:Published
Refereed:Yes
Uncontrolled Keywords:Tuberculosis, DNA vaccines, mycobacterium
Subjects:Area 06 - Scienze mediche > MED/07 Microbiologia e microbiologia clinica
Area 07 - Scienze agrarie e veterinarie > VET/03 Patologia generale e anatomia patologica veterinaria
Divisions:001 Università di Sassari > 01 Dipartimenti > Patologia e clinica veterinaria
001 Università di Sassari > 01 Dipartimenti > Scienze biomediche
Publisher:Elsevier Masson
ISSN:1286-4579
Deposited On:18 Aug 2009 10:06

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