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.


Available from: Simone G Ramos, Apr 27, 2015
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Intranasal delivery of DNA vaccines has become a popular research area recently. It offers some distinguished advantages over parenteral and other routes of vaccine administration. Nasal mucosa as site of vaccine administration can stimulate respiratory mucosal immunity by interacting with the nasopharyngeal-associated lymphoid tissues (NALT). Different kinds of DNA vaccines are investigated to provide protection against respiratory infectious diseases including tuberculosis, coronavirus, influenza and respiratory syncytial virus (RSV) etc. DNA vaccines have several attractive development potential, such as producing cross-protection towards different virus subtypes, enabling the possibility of mass manufacture in a relatively short time and a better safety profile. The biggest obstacle to DNA vaccines is low immunogenicity. One of the approaches to enhance the efficacy of DNA vaccine is to improve DNA delivery efficiency. This review provides insight on the development of intranasal DNA vaccine for respiratory infections, with special attention paid to the strategies to improve the delivery of DNA vaccines using non-viral delivery agents.
    Pharmaceutics 09/2014; 6(3):378-415. DOI:10.3390/pharmaceutics6030378
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Despite worldwide availability of the vaccines against most of the infectious diseases, BCG and various programs such as Directly Observed Treatment Short course (DOTS) to prevent tuberculosis still remains one of the most deadly forms of the disease affecting millions of people globally. The evolution of multi drug resistant strains (MDR) has increased the complexity further. Although currently available marketed BCG vaccine has shown sufficient protection against childhood tuberculosis, it has failed to prevent the most common form of disease i.e., pulmonary tuberculosis in adults. However, various vaccine candidates have already entered phase I clinical trials and have shown promising outcomes. The most prominent amongst them is the heterologous prime-boost approach, which shows a great promise towards designing and development of a new efficacious tuberculosis vaccine. It has also been shown that the use of various viral and non-viral vectors as carriers for the potential vaccine candidates will further boost their effect on subsequent immunization. In this review, we briefly summarize the potential of a few novel nano-carriers for developing effective vaccination strategies against tuberculosis.
    European journal of pharmaceutical sciences: official journal of the European Federation for Pharmaceutical Sciences 06/2014; DOI:10.1016/j.ejps.2014.05.028 · 3.01 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Schistosomiasis is one of the most important neglected diseases found in developing countries and affects 249 million people worldwide. The development of an efficient vaccination strategy is essential for the control of this disease. Previous work showed partial protection induced by DNA-Sm14 against Schistosoma mansoni infection, whereas DNA-Hsp65 showed immunostimulatory properties against infectious diseases, autoimmune diseases, cancer and antifibrotic properties in an egg-induced granuloma model.
    BMC Infectious Diseases 05/2014; 14(1):263. DOI:10.1186/1471-2334-14-263 · 2.56 Impact Factor