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

Núcleo de Pesquisas em Tuberculose, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, São Paulo,
BMC Immunology (Impact Factor: 2.25). 07/2008; 9:38. DOI: 10.1186/1471-2172-9-38
Source: PubMed

ABSTRACT 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.
We developed a novel and non-toxic formulation of cationic liposomes, in which the DNA-hsp65 vaccine was entrapped (ENTR-hsp65) or complexed (COMP-hsp65), and used to immunize mice by intramuscular or intranasal routes. Although both liposome formulations induced a typical Th1 pattern of immune response, the intramuscular route of delivery did not reduce the number of bacilli. However, a single intranasal immunization with COMP-hsp65, carrying as few as 25 microg of plasmid DNA, leads to a remarkable reduction of the amount of bacilli in lungs. These effects were accompanied by increasing levels of IFN-gamma and lung parenchyma preservation, results similar to those found in mice vaccinated intramuscularly four times with naked DNA-hsp65 (total of 400 microg).
Our objective was to overcome the significant obstacles currently facing DNA vaccine development. Our results in the mouse TB model showed that a single intranasal dose of COMP-hsp65 elicited a cellular immune response that was as strong as that induced by four intramuscular doses of naked-DNA. This formulation allowed a 16-fold reduction in the amount of DNA administered. Moreover, we demonstrated that this vaccine is safe, biocompatible, stable, and easily manufactured at a low cost. We believe that this strategy can be applied to human vaccines to TB in a single dose or in prime-boost protocols, leading to a tremendous impact on the control of this infectious disease.

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    • "Although DNA vaccines have been shown to induce a potent CTL responses (Srivastava and Liu, 2003), but they are not capable enough in eliciting antibody responses (Wang et al., 1998), and low immunogenicity has been observed in human clinical trials as well (Bivas-Benita et al., 2009). This low immunogenicity of DNA vaccines may be addressed by the use of various novel delivery systems coupled with suitable adjuvants for DNA vaccines (Bivas-Benita et al., 2004, 2009; de la Torre et al., 2009; Meerak et al., 2013; Rosada et al., 2008, 2012; Wang et al., 2010; Yu et al., 2012) (Table 4). Thus strategies are needed to enhance the immunogenicity of DNA vaccines (Yu et al., 2012). "
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