Pulmonary delivery of DNA encoding Mycobacterium tuberculosis latency antigen Rv1733c associated to PLGA–PEI nanoparticles enhances T cell responses in a DNA prime/protein boost vaccination regimen in mice

Bivas-Benita, Maytal; Lin, May Young; Bal, Suzanne M.; van Meijgaarden, Krista E.; Franken, Kees L.M.C.; Friggen, Annemieke H.; Junginger, Hans E.; Borchard, Gerrit; Klein, Michèl R.; Ottenhoff, Tom H.M.

doi:10.1016/j.vaccine.2009.04.033

Scientific article

English

Pulmonary delivery of DNA encoding Mycobacterium tuberculosis latency antigen Rv1733c associated to PLGA–PEI nanoparticles enhances T cell responses in a DNA prime/protein boost vaccination regimen in mice

ContributorsBivas-Benita, Maytal; Lin, May Young; Bal, Suzanne M.; van Meijgaarden, Krista E.; Franken, Kees L.M.C.; Friggen, Annemieke H.; Junginger, Hans E.; Borchard, Gerrit

; Klein, Michèl R.; Ottenhoff, Tom H.M.

Published inVaccine, vol. 27, no. 30, p. 4010-4017

Publication date2009

Abstract

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.

Keywords

DNA vaccine
Tuberculosis latency antigens
Pulmonary immunization
PLGA-PEI nanoparticles
T cell response

Affiliation entities

Faculté des sciences / Section des sciences pharmaceutiques

Citation (ISO format)

BIVAS-BENITA, Maytal et al. Pulmonary delivery of DNA encoding Mycobacterium tuberculosis latency antigen Rv1733c associated to PLGA–PEI nanoparticles enhances T cell responses in a DNA prime/protein boost vaccination regimen in mice. In: Vaccine, 2009, vol. 27, n° 30, p. 4010–4017. doi: 10.1016/j.vaccine.2009.04.033

Identifiers

PID : unige:18729
DOI : 10.1016/j.vaccine.2009.04.033

Additional URL for this publicationhttp://linkinghub.elsevier.com/retrieve/pii/S0264410X09005787

Journal ISSN0264-410X

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Pulmonary delivery of DNA encoding Mycobacterium tuberculosis latency antigen Rv1733c associated to PLGA–PEI nanoparticles enhances T cell responses in a DNA prime/protein boost vaccination regimen in mice

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