Home  Biological Terrorism  Epidemiology  Pathology
Treatment  Vaccines  References

Vaccines - Future Developments

Novel vaccines

Stimulated by concern over its potential as a weapon of bioterrorism there has been a push to develop better vaccines to Anthrax. The gene encoding PA (pag) has recently been cloned into Bacillus subtilis. This has allowed scientists to obtain higher yields of PA free from other toxin components, EF and LF. This has also resulted in less stringent needs for rigorous containment (13).

Along a different tact, some groups have performed studies using PA and new adjuvants. The studies did not mention any adverse affects in the animals recieving the adjuvants. Amoung the most promising is an adjuvant called Ribi Tri-Mix. It is reported to induce stimulation of the cell mediated arm of the immune system. Indeed, animals recieving PA and Ribi Tri-Mix not only survived anthrax challenge but also failed to show any signs of the limited bacteremia that was experienced by animals that received other adjuvants (13) (14) (12).

Studies are also proceeding along DNA vaccine lines. Mi-Li Gu et al have vaccinated mice with a plasmid encoding PA. Mice innoculized three times at three week intervals were tested for the presence of antibodies two weeks after each innoculation. After the third immunization the mice demonstrated the presence of a significant concentration of anti-PA in their serum.

Furthermore, DNA vaccination increased the number of IFN-gamma and IL-4 cytokine secreting cells by four fold. IFN-gamma is a cytokine of the Th1 pathway whereas IL-4 is a cytokine of the Th2 pathway. Thus there is the possibility of an increased cell-mediated response as compared to AVA. These mice were protected when challenged with lethal doses of LF + PA. Unfortunately, because the authors didn't have access to adequate containment facilities, they were unable to perform challenges with virulent Bacillus anthracis (15).

In the next few years some of these studies will most likely enter clinical trials. Another idea that is in the process of being developed involves the use of PA as a vehicle to direct extracellular proteins to the cytosol. where they could be shuttled into the MHC I processing pathway. This would enable the researcher to more directly stimulate the cell-mediated arm of the immune system (20).