期刊
VACCINE
卷 27, 期 30, 页码 4010-4017出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.vaccine.2009.04.033
关键词
DNA vaccine; Tuberculosis latency antigens; Pulmonary immunization; PLGA-PEI nanoparticles; T cell response
资金
- Foundation Microbiology Leiden
- European Commission [LSHP-CF-2003-503367]
- Bill and Melinda Gates Foundation
- Grand Challenges in Global Health [GC12 82]
- ISA Pharmaceuticals B.V., Bilthoven, The Netherlands
During persistent infection and hypoxic-stress, Mycobacterium tuberculosis (Mtb) expresses a series of Mtb latency antigens. The aim of this study was to evaluate the immunogenicity of a DNA vaccine encoding the Mtb latency antigen Rv1733c and to explore the effect of pulmonary delivery and co-formulation with Poly (D,L-lactide-co-glycolide) (PLGA)-polyethyleneimine (PEI) nanoparticles (np) on host immunity. Characterization studies indicated that PLGA-PEI np kept their nanometer size after concentration and were positively charged. The np were able to mature human dendritic cells and stimulated them to secrete IL-12 and TNF-alpha comparable to levels observed after lipopolysaccharide (LPS) stimulation. Mtb latency antigen Rv1733c DNA prime combined with Rv1733c protein boost enhanced T cell proliferation and IFN-gamma secretion in mice in response to Rv1733c and Mtb hypoxic lysate. Rv1733c DNA adsorbed to PLGA-PEI np and applied to the lungs increased T cell proliferation and IFN-gamma production more potently compared to the same vaccinations given intramuscularly. The strongest immunogenicity was obtained by pulmonary priming with np-adsorbed Rv1733c DNA followed by boosting with Rv1733c protein. These results confirm that PLGA-PEI np are an efficient DNA vaccine delivery system to enhance T cell responses through pulmonary delivery in a DNA prime/protein boost vaccine regimen. (C) 2009 Elsevier Ltd. All rights reserved.
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