Future of Infection Fighting

Current antibiotics are fast becoming useless with few new ones in the pipeline. All is not lost though, there is much research going into finding alternatives. One of these alternatives is the old fashioned way of fighting infections. Before the discovery of effective and relatively safe antibiotics doctors often relied on what was called ‘antiserum’.  

Antiserum was made by filtering out the cells and clotting factors from blood and leaving the antibodies. The blood was usually obtained from horses that had been infected with the agent (or agents) that the antiserum was desired for. Though the source of the blood varied and whenever possible an animal that was not affected by the pathogen was used because they could receive high levels of the infecting agent without becoming ill and thus produce more antiserum. Antiserum was also obtained from people who had either recovered from the illness or were vaccinated against it.

As of 1921 the effectiveness of antisera varied greatly1. Since in most cases how exactly the antiserum worked was unknown it is impossible to make a conclusion for why this was so and whether or not it can be improved upon. It was believed at the time that one possible reason was that the antiserum was only effective against specific strains of a pathogen. Support for this theory came from the fact that when it was possible to identity a specific strain and provide an antiserum for that strain mortality was greatly reduced (compared to just giving one antiserum for all cases). Additionally, the effectiveness of various antisera varied from region and outbreaks. The fewer strains of a pathogen  found the more likely the antiserum would be effective.

Finding the source and solutions to the variable effectiveness of past antisera is critical in today's world were someone could become infected with a pathogen in New York but not show symptoms until in Hong Kong. If that pathogen is not common in Hong Kong the local doctors will not be able to aid that individual. Luckily, research  and use of antisera did not stop completely with the use of antibiotics.  

Today antiserum is still used and goes by the name immunoglobulin therapy. Currently used mainly for autoimmune, immunodeficiency or inflammatory diseases2. Today the antibodies are obtained from people who have been vaccinated.

Clinicians also depend upon antisera to fight many viral infections. Antisera is currently the recommended treatment for human rabies3  and is used to fight Hepatitis B infections4. Researchers have recently discovered a possible universal vaccine for ‘influenza A’ and possibly a way to fight an existing ‘influenza A’ infection by studying the antibodies produced by those previously infected with influenza or vaccinated5.

One thing is certain. Fighting bacterial infections in the future will be more expensive. Monitoring bacterial infections in the population will become more critical to ensure the proper antisera are available in sufficient quantities.

Though more expensive there are advantages to using antisera. One, pathogens will not be able to develop resistance to the antisera. Two, if the use of antisera against viruses is any indication there should be fewer adverse effects from disrupting local beneficial bacteria6.

Even if bacteria where not developing resistance faster then we can find new antibiotics there use is bound to become outdated. Physicians prescribe as narrow an antibiotic as possible but it is impossible to not end up harming helpful bacteria and antibiotic use has been linked to numerous health problems resulting form the disruption of bacterial flora. In the future it will be possible to scan an isolated pathogen and have a computer design and manufacture an inhibitor. As with the example of ‘Influenza A’ research for the design of these computer generated inhibitors will be informed by the mechanisms of effective antisera.  The technology already exists to determine if a molecule is a likely toxin7,8.Eventually, production will cease to be centralized as the technology becomes cheaper allowing for more local control and production of more efficient antibodies for every situation.

J.A. Gibbons
References:

1. Principles of immunology. Howard Thomas Karsner. J.B. Lippincott Co., 1921

2. Current uses of immunoglobulin therapy and side effects  

3. CDC on rabies

4. Hepatitis B immune globulin and HBV-related liver transplantation. Akay S, Karasu Z. Expert Opinion on Biological Therapy.  2008 Nov;8(11):1815-22.

5. One antibody to bind them all. Marian Turner Nature News. 28 July 2011.

6. At least it won't hurt: the personal risks of antibiotic exposure.Stewardson AJ, Huttner B, Harbarth S.Curr Opin Pharmacol. 2011 Jul 18.

7. Towards rational molecular design: derivation of property guidelines for reduced acute aquatic toxicity. Adelina M. Voutchkova, Jakub Kostal, Justin B. Steinfeld, John W. Emerson, Bryan W. Brooks, Paul Anastas and Julie B. Zimmerman
Green Chem., 2011, Advance Article DOI:  10.1039/C1GC15651A  

8. Toward molecular design for hazard reduction—fundamental relationships between chemical properties and toxicity. Adelina M. Voutchkovaa, Lori A. Ferrisb, Julie B. Zimmermanb, c and Paul T. Anastas. Volume 66, Issue 5, 30 January 2010, Pages 1031-1039.
Advances in Green Chemistry