Protection against tuberculosis by a single intranasal administration of DNA-hsp65 vaccine complexed with cationic liposomes

Abstract

Background: The greatest challenges in vaccine development include optimization of DNA vaccines for use in humans, creation of effective single-dose vaccines, development of delivery systems that do not involve live viruses, and the identification of effective new adjuvants. Herein, we describe a novel, simple technique for efficiently vaccinating mice against tuberculosis (TB). Our technique consists of a single-dose, genetic vaccine formulation of DNA-hsp65 complexed with cationic liposomes and administered intranasally.

Present status of nanoparticle research for treatment of Tuberculosis

“…Cationic liposomes entrapped antigenic tuberculosis ESAT-6 protein and complexed with TLR agonists were evaluated for use as a prophylactic vaccine system by Zaks research group [15]. They found to have considerable protective immunity after an aerosol challenge with virulent Mycobacterium tuberculosis [16]. Nanoscale aerosol vaccines for tuberculosis have also been developed which can perfuse throughout the respiratory pathway and also increase the amounts of drug reaching to the target alveoli.…”

Technological Aspects of Scalable Processes for the Production of Functional Liposomes for Gene Therapy

“…Moreover, this formulation was demonstrated to be safe, biocompatible, stable, and easy to manufacture at low cost. We think that this strategy can be applied to human vaccination against TB in a single dose or in prime-boost protocols with a tremendous impact on controlling this neglected disease (Rosada et al, 2008). The net positive surface charge imparted by DOTAP drives electrostatic binding to the cell membrane.…”

“…However, to the best of our knowledge, no study has yet focused on the approach connecting design, product, and production process. We obtained promising immunological responses and a prophylactic effect against tuberculosis (TB) using cationic dehydrated-hydrated liposomes (DRV) complexed to DNA containing the hsp65 gene on the external surface (Rosada et al, 2008). Hsp65 is a heat shock protein from M. leprae.…”

“…The hsp65 gene has been extensively studied and its biological effects evaluated for protection against and the treatment of tuberculosis (de Paula et al, 2007;Silva et al, 2005). Formulations based on the hsp65 gene have been used in different immunization strategies and the evaluation of protection against M. tuberculosis challenge (Souza et al, 2008). We developed a novel and non-toxic formulation of cationic liposomes in which the hsp65 DNA vaccine was entrapped or complexed on the external surface of the cationic DRV.…”

“…The liposomes were prepared using Bangham's method (Bangham et al, 1965) and characterized according to size, polydispersity, and zeta potential. DNA loading and availability on the external surface of liposomes were also determined (Rosada et al, 2008). For the next pre-clinical and clinical assays, a scalable process had to be established in order to evaluate the capability of the system in scale transposition, reproducing the physico-chemical and biological properties of the previously prepared liposomes on a laboratory scale.…”