The Next Plague: How to tame viruses

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Viruses can be controlled with vaccines and antiviral drugs. Vaccines have a terrific track record at controlling many of the most obnoxious viruses seen in the world. These include vaccines for smallpox, influenza, hepatitis A & B, human papilloma virus, mumps, chickenpox/zoster, poliomyelitis, rabies, tick-borne encephalitis, yellow fever (a potentially hemorrhagic infection), Japanese encephalitis, measles and rotavirus. Unfortunately, viruses can be very sloppy during replication, leading to rapid development of resistance to antiviral drugs and an inability to generate a vaccine because no stable epitope exists on the virus surface to which the immune system can react. Also, viruses can persist in body sanctuaries like the nervous system only to re-emerge later. Shingles and cold sores are just such creatures. These cloaked viruses can rapidly emerge and become life-threatening should the individual become immunosuppressed because of an uncontrolled HIV co-infection, immune suppression with an organ transplant drug or during treatment of cancer with chemotherapy.  Of major concern for infectious diseases in general are the long timelines to create antiviral drugs and vaccines and their subsequent cost burden to the healthcare system. It took 33 years from the identification of hepatitis C virus until novel drugs were invented that cured the disease. These anti-HCV drugs cost the healthcare system $80,000 to $100,000 per cure. Between 130–150 million people globally have chronic hepatitis C infection. A significant number of those who are chronically infected will develop liver cirrhosis or liver cancer. Approximately 700,000 people die each year from hepatitis C-related liver diseases. The state of vaccine development is summarized below:   

  • Thirty years ago, 35 companies produced vaccines for use in the United States. Between 1988 and 2001, 10 of 14 global vaccine manufacturers partially or completely stopped production of traditional childhood vaccines.
  • Virtually all licensed vaccines in the United States are now produced by just a handful of pharmaceutical companies: GlaxoSmithKline, Merck, Novartis, Sanofi Pasteur, and Pfizer. These companies account for 80 percent of the worldwide vaccine market.
  • Between late 2000 and 2003, there were unprecedented and unanticipated shortages of eight of 11 vaccines routinely administered to children.
  • Factors that discourage vaccine research and development include limited demand, legal liability concerns, and price limits because of bulk purchasing. Perhaps the largest obstacles to the development of vaccines are the cost and time necessary to shepherd a vaccine through the clinical research process to licensure.
  • The 1986 National Childhood Vaccine Injury Act is a law designed in part to protect vaccine manufacturers against safety-related financial liability. This surcharge accounts for >25% of the cost of a dose of DPT vaccine.
  • Producing a safe and effective vaccine requires about 12-15 years of research and costs estimated between $500 million and $1 billion dollars. This financial landscape means that vaccines neither pay for themselves nor turn a profit, rendering it unlikely that the industry will continue to invest in them unless they have a great volume, can charge an astronomical price and/or require ongoing dosing.
  • It is estimated that 60 percent of vaccine production costs are fixed, meaning they are incurred regardless of the amount of product produced. Vaccines require a sizable market to be profitable at all.
  • Phase III trial for rotavirus vaccine, RotaTeq, required testing in 70,000 children in 11 countries and cost $350,000,000

Certain viruses will never be controlled/prevented by a vaccine, because they are just too genetically fluid to allow the creation of a viable vaccine. HIV is a classic example of a very genetically unstable virus. Influenza is also in this category, but one-year vaccines are possible. Each flu season the virus re-emerges from its water fowl and swine hosts with a relatively stable surface epitope for vaccines to mimic. However, the influenza virus surface antigens are re-scrambled and mutated in their animal hosts each year or so, resulting in the next year’s influenza virus being sufficiently altered such that a new vaccine will need to be prepared.

The case of a mysterious virus, encephalitis lethargica, suddenly appearing to wreak havoc on the brains of those it infected, was portrayed in the overly dramatic movie, Awakenings. This virus disappeared as rapidly as it materialized. This total unpredictability is what makes it so difficult to plan for a viral assault by something never seen before. Surveillance of emerging viruses by the global health services will pick these new viruses up fairly early in their existence, which is how we identified Zika in Africa as far back as 1947. However, we were still very surprised by its sudden and frightening emergence in 2016 an ocean away in South America.

 Viruses are among the favorite biological warfare agents in the BW community because of their potential for rapid dissemination in human populations and their disabling effects, including death. The lead candidates for BW weaponized viruses include smallpox, the hemorrhagic viruses listed above especially, Ebola, Marburg (which the USSR weaponized in the 80s) and dengue, various strains of encephalitis viruses, including the colorfully named Russian Spring-summer, Parrot fever and yellow fever.   

Viruses are some of the most dangerous infectious agents on earth. They are in continual evolutionary flux with the constant possibility of emerging from their native host organisms to threaten human health and survival. This is quite remarkable for what is essentially a non-living chemical bag of enzymes, virulence factors, molecular machines and genetic material. Viruses can commandeer living cells and chemically reproduce new generations of nonliving molecular bags of enzymes, virulence factors, molecular machines and genetic material and in so doing ultimately dispatch human life.