DNA Vaccine for the Prevention and Treatment fo Tuberculosis

Tradicional systems for developing drugs and vaccines are failing spectaculary to deliver the goods in the fight against tuberculosis (TB). The disease that afflicts the developing world defies the imagination in its scale. One third of the world's population - 2 billion people - is infected with Mycobacterium tuberculosis, and 16 million have active TB. Shockingly, TB hit an all-time high in 1999 with 8 million new cases - 95 per cent of them in developing countries - and 2 million deaths. The disease is spreading rapidly throughout the world. The toll is set to rise; AIDS activates the dormant form of the disease, while multidrug resistance is spreading across the planet. The last new drug for TB was introduced over thirty years ago and industry has been reluctant to invest in discovering new families of drugs because of the financial risks in investing in products destined largely for developing country markets. If global health is left to market forces, historians will remember this era as one in which humanity stood idly by while half the planet languished in sickness. Fortunately some researchers have realized this, and are driving forward new models for TB therapy and vaccine discovery. One of the latest sign of this trend is the development of a DNA vaccine for the prevention and treatment of TB by our research group. Over the last few years, some of our experiments in wich mycobacterial antigens were presented to the immune system, as of they were viral antigens (DNA vaccine), have had a significant impact on our understanding of protective immunity against tuberculosis. They also markedly enhanced the prospects for new vaccines. We now know that individual mycobacterial-protein antigens expressed from DNA-vaccine constructs can confer protection equal to that from live BCG vaccine in mice. A critical determinant of the outcome of immunization appears to be the degree to which antigen-specific cytotoxic T cells are generated by the immune response. We have demonstrated that DNA vaccination is an affective way of establishing long lasting cytotoxic T-cell memory and protection against tuberculosis. Moreover, our new preclinical work shows that DNA vaccines, initially designed to prevent infection, can also have a dramatic therapeutic action. In infected mice, the immune response can be caused to switch from one that is relatively inefficient and gives bacterial stasis to one that kills the bacteria, eliminating...

Poly-DL-lactide-co-glycolide microspheres as a controlled release antigen delivery system

Successful vaccine application means maximum protection with minimal number of administrations. A rational development of vaccines involves studies of the nature of the antigen as well as of the adjuvant to be used to improve the immune responses. This has provided the impetus for studies to design the degradable devices and for different approaches to antigen delivery by different routes of administration. The development of controlled release systems based on polymeric devices that permit a sustained or pulsed release of encapsulated antigens has attracted much interest. Polymeric delivery systems consist of polymers that release their content continuously in a controlled manner over a period of time. The development of a biocompatible delivery system for parenteral administration offers several advantages in terms of immunoadjuvanticity over other compounds. It was found that, in contrast to other carriers, microspheres are more stable, thus permitting administration by the oral or parenteral route. In the present study, we describe the main characteristics and potentialities of this new immunoadjuvant for oral and parenteral administration