DNA-launched alphavirus replicons encoding a fusion of mycobacterial antigens Acr and Ag85B are immunogenic and protective in a murine model of TB infection

Dalmia, N and Klimstra, WB and Mason, C and Ramsay, AJ (2015) DNA-launched alphavirus replicons encoding a fusion of mycobacterial antigens Acr and Ag85B are immunogenic and protective in a murine model of TB infection. PLoS ONE, 10 (8).

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Abstract

There is an urgent need for effective prophylactic measures against Mycobacterium tuberculosis (Mtb) infection, particularly given the highly variable efficacy of Bacille Calmette-Guerin (BCG), the only licensed vaccine against tuberculosis (TB). Most studies indicate that cell-mediated immune responses involving both CD4+ and CD8+ T cells are necessary for effective immunity against Mtb. Genetic vaccination induces humoral and cellular immune responses, including CD4+ and CD8+ T-cell responses, against a variety of bacterial, viral, parasitic and tumor antigens, and this strategy may therefore hold promise for the development of more effective TB vaccines. Novel formulations and delivery strategies to improve the immunogenicity of DNA-based vaccines have recently been evaluated, and have shown varying degrees of success. In the present study, we evaluated DNA-launched Venezuelan equine encephalitis replicons (Vrep) encoding a novel fusion of the mycobacterial antigens α-crystallin (Acr) and antigen 85B (Ag85B), termed Vrep-Acr/Ag85B, for their immunogenicity and protective efficacy in a murine model of pulmonary TB. Vrep-Acr/Ag85B generated antigen-specific CD4+ and CD8+ T cell responses that persisted for at least 10 wk post-immunization. Interestingly, parenterally administered Vrep-Acr/Ag85B also induced T cell responses in the lung tissues, the primary site of infection, and inhibited bacterial growth in both the lungs and spleens following aerosol challenge with Mtb. DNAlaunched Vrep may, therefore, represent an effective approach to the development of genebased vaccines against TB, particularly as components of heterologous prime-boost strategies or as BCG boosters.

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Details

Item Type:	Article
Status:	Published
Creators/Authors:	Creators Email Pitt Username ORCID Dalmia, N Klimstra, WB klimstra@pitt.edu KLIMSTRA Mason, C Ramsay, AJ
Contributors:	Contribution Contributors Name Email Pitt Username ORCID Editor Tyagi, Anil Kumar UNSPECIFIED UNSPECIFIED UNSPECIFIED
Date:	28 August 2015
Date Type:	Publication
Access Restriction:	No restriction; Release the ETD for access worldwide immediately.
Journal or Publication Title:	PLoS ONE
Volume:	10
Number:	8
DOI or Unique Handle:	10.1371/journal.pone.0136635
Institution:	University of Pittsburgh
Schools and Programs:	School of Medicine > Microbiology and Molecular Genetics
Refereed:	Yes
Date Deposited:	23 Aug 2016 14:37
Last Modified:	30 Mar 2021 17:55
URI:	http://d-scholarship.pitt.edu/id/eprint/28392

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