Future Treatment: Immune Modulation

Septic Infection (Credit: CDC)

Instead of strictly offensive measures (e.g. antivirals, antibiotics, and siRNA treatments), scientists are developing ways to improve our own natural defense against pathogens, our immune system.  This can be done both by enhancing immune function and preventing immune overreactions.

Enhancing the Immune System

A study released last month found a way to protect mice from deadly doses of Yersinia pestis (plague), Burkholderia pseudomallei (melioidosis), Brucella abortus (brucellosis), and Francisella tularensis (tularemia).  All of these agents are Select Agents and possible bioweapons agents.  Researchers from a branch of the National Institute of Allergy and Infectious Diseases (NIAID) branch in Montana were able confer this protection by enhancing the immune response in mice, priming it to fight an infection.  When the researchers administered a mixture of F. tularensis membrane proteins and an adjuvant, an agent used in vaccines to enhance the immune response, 3 days before a lethal dose of F. tularensis, B. psuedomallei, or B. abortus, the mice survived.  The director of NIAD, Anthony S. Fauci, M.D., stated that, “A therapeutic that protects against a wide array of bacterial pathogens would have enormous medical and public health implications for naturally occurring infections and potential agents of bioterrorism,” in reference to the results.  Although true, this statement is somewhat misleading considering the immune enhancing treatment had to be given at least three days before infection or the mice would die. Therefore, the treatment was prophylactic, not therapeutic.  A treatment such as this could be used by decontamination teams or laboratory workers as an extra level of precaution in the wake of a biological attack with a known or unknown agent.

Subduing the Immune System
This potential treatment could save hundreds of thousands of lives a year, by suppressing some immune cells.  In response to a bacterial, viral or fungal infection that is septic (present throughout the body), the immune response may become hyper-active, releasing many pro-inflammatory molecules that can put the body in a state of “septic shock.”  Once in this state, chances of death greatly increase.  Many diseases can lead to this state, including tularemia, the 1918 (H1N1) flu, anthrax, Ebola and smallpox.  Researchers have found that by blocking one enzyme, sphingosine kinase 1 (SphK1), in infected mice, they were able to prevent septic shock. This effect was enhanced when used with an antibiotic.  Currently, a massive dose of antibiotics is prescribed to treat bacterial sepsis, which can be harmful to the liver.  In a few years, this treatment could be in clinical trials.  A Science magazine podcast with a researcher who helped develop this treatment can be found here.

Conclusion
With most diseases, including anthrax, early treatment can be the difference between life and death, but diagnostic tests used to positively identify and characterize the resistance(s) of a specific agent (or cocktail of agents) can take days, often delaying the most effective treatment regime.  This is why broad spectrum treatments similar to those discussed above are important, they can be used immediately and effectively before the disease agent is characterized.  Immune modulating treatments will likely become a common treatment method, since a healthy immune system is highly effective (more than 99% of all infections are destroyed by the innate immune system, before one becomes “sick”).  Our natural immune system is also more dynamic and specific than any engineered human response.  Infectious disease and immunology research by academia and the biotechnology industry will continue to produce life saving advances in the years to come.

While beneficial, all technological advances have the potential for misuse, and a continual effort to raise the awareness of these issues to scientists and the community is needed.  The FAS Biosecurity program’s dual use case studies highlight some research related to the topics mention in this post, including a Drug Delivery case study and an immune modulation related “Mousepox Case Study.”

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