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J Infect Dis. 2013 Apr 15;207(8):1242-52. doi: 10.1093/infdis/jis425. Epub 2012 Aug 13.

Therapeutic immunization against Mycobacterium tuberculosis is an effective adjunct to antibiotic treatment.

Author information

1
Infectious Disease Research Institute, Seattle, Washington, USA.

Abstract

BACKGROUND:

Recent advances in rational adjuvant design and antigen selection have enabled a new generation of vaccines with potential to treat and prevent infectious disease. The aim of this study was to assess whether therapeutic immunization could impact the course of Mycobacterium tuberculosis infection with use of a candidate tuberculosis vaccine antigen, ID93, formulated in a synthetic nanoemulsion adjuvant, GLA-SE, administered in combination with existing first-line chemotherapeutics rifampicin and isoniazid.

METHODS:

We used a mouse model of fatal tuberculosis and the established cynomolgus monkey model to design an immuno-chemotherapeutic strategy to increase long-term survival and reduce bacterial burden, compared with standard antibiotic chemotherapy alone.

RESULTS:

This combined approach induced robust and durable pluripotent antigen-specific T helper-1-type immune responses, decreased bacterial burden, reduced the duration of conventional chemotherapy required for survival, and decreased M. tuberculosis-induced lung pathology, compared with chemotherapy alone.

CONCLUSIONS:

These results demonstrate the ability of therapeutic immunization to significantly enhance the efficacy of chemotherapy against tuberculosis and other infectious diseases, with implications for treatment duration, patient compliance, and more optimal resource allocation.

PMID:
22891286
PMCID:
PMC3693588
DOI:
10.1093/infdis/jis425
[Indexed for MEDLINE]
Free PMC Article

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