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The Story of a Successful Virus

The Story of a Successful Virus

Jun 1, 2010

The H1N1 09  Virus: The First Pandemic of the 21st Century.

A historic announcement in April 2009 caused global panic and brought immediate attention to the state of public health.  The Mexican Secretariat of Health reported an outbreak of respiratory disease that was later classified as a novel swine origin influence A, H1N1 09.  The WHO quickly responded:

“a strong signal that a pandemic is imminent and that the time to finalize the organization, communication and implementation of the planned mitigation measure is short1”  

During the beginning of the 20th century, the historic Spanish Flu, a molecularly similar strain to the 2009 H1N1, caused 500 million known cases of infection and 50 million casualties worldwide.  Today, collaboration between pharmaceutical companies and government organizations represents our main line of defense against pandemics. As human global travel has dramatically increased, so has the ability for these deadly viruses to infect a widespread population. In response, private companies and government agencies have invested heavily in understanding the mechanisms responsible for the spread of these deadly influenza strains.  Ahead of schedule, Novartis announced in June of 2009 that they had successfully created the first batch of swine flu vaccine in Germany.  To support a government initiative in the United States to provide an H1N1 vaccine to its entire population, Novartis quickly ramped up production with an investment of approximately 290 million dollars.

Biologically, there were surprisingly many structural similarities between the 1918 pandemic H1N1 virus and the 2009 strain.

Why wouldn’t selective pressures cause the 2009 strain to be significantly different ( in terms of its biologic structures)from its distantly related 1918 strain?  The answer is two fold: First, based on the structure of the 1918 HA, it is evident that the region in which immune antibodies for the original 1918 strain were glycosylated2.  Glycosylation is a key evolutionary phenomenon that allowed this 91-year-old virus to evade human immunity, specifically B cell immunity by masking viral proteins and inhibiting immune antibodies from identifying and binding to them.  The second reason for similarities between the two strains is that influenza life cycle varies across different animal species.  In swine models, viruses have short life cycles and have fewer repeat infections.  Therefore, they can remain dormant and experience very few genetic modifications in the species whereas in the human population, influenza is common and therefore, there are numerous strains that enter the population.  As human seasonal strains evolve, thus becoming less similar to the 1918 swine flu virus, fewer people have protective antibodies to old viruses.  Therefore, it became an advantageous landscape for a swine flu strain with similar properties as the 1918 strain to emerge and establish itself as a pandemic.

It was notably devastating for the younger generation.  Nearly 35% of individuals over 60 had antibodies to neutralize the 2009 pandemic.  This may reflect a prior infection, with a strain similar to that of 1918, or immunization against the 1976 swine flu strain.  However, the majority of the population did not carry antibodies, and were therefore susceptible to serious adverse effects of the virus2.

Successful Diagnostic Tools for Identifying 2009’s A H1N1

Early detection is critical in protecting individuals from severe flu symptoms and curbing the spread of the disease.  Diagnostic tools were rapidly developed during the 2009 flu pandemic.  Two strategies emerged as the most successful.

Viral Culture Technology:  Diagnostic Technology, a San Diego based life science company, received FDA Emergency Use Authorization (EUA) approval on February 2010 for its H1N1 diagnostic tool. Diagnostic Technology was able to leverage its unique platform, D3 fluorescent labeled antibody technology, to quickly engineer a monoclonal antibody fluorescent staining kit to identify the 2009 H1N1 Influenza A.  Its expertise in respiratory testing provided credibility and security that enabled this test to receive fast approval from the FDA3.

Real Time Polymerase Chain Reaction (RT-PCR):  RT-PCR allows for one to find specific diagnostic targets by analyzing the genome to confirm infection in patients.  In the case of H1N1, the  RT-PCR assays  have target-specific oligonuclotides to all H1N1 viruses to find even small amounts of A H1N1 viral RNA in patients.  The first generation assays were developed through the first identified A H1N1 (2009) genomic sequences.  With more cases identified, this diagnostic test will be redesigned to incorporate all the variations in the genomic sequences found throughout the population4,5.  Focus Diagnostics, a subsidiary of Quest Diagnostics, released its Simplexa Influenza A H1N1 (2009) test, a test based on the RT-PCR technology platform.  The test, receiving both EUA and the approval to be used in CLIA (*) certified laboratories, was designed for the 3M Integrated Cycler and therefore did not require additional lab capacity for its use.

Future Outlook

The primary challenge on the influenza public health agenda is to prevent future pandemics.  The lessons learned from this most recent pandemic would help us to anticipate and develop effective strategies.  The main lesson from the successes and failures of the 2009 emergency response is that influenza does not create entirely new viral strains, but rather recycles past strains that have been forgotten by the human immune system.  Therefore, developing vaccine strategies that target viruses present in animal reservoirs and harvesting antiquated vaccines could collectively help us prevent futurepandemics.  Technological advancements, such as diagnostics, play a key role in promoting global health.


Notes

(*) CLIA, or Clinical Laboratory Improvement Amendments, was passed in 1988 and established quality standards for all laboratory testing to ensure accuracy, reliability and timeliness of patient test results regardless of where the test is performed.  A CLIA certified laboratory is a laboratory that has meet all the guidelines stated in the 1988 amendment and is granted CLIA status from the FDA.


References

  1. Seal, et.al.  Why do I need it?  I am not at Risk!  Public perceptions towards the pandemic (H1N1) 2009 vaccine.  BMC Infectious Diseases.  2010, 10:99.
  2. Settembre E.C. et.al.  H1N1: Can a Pandemic Cycle be Broken?  Science Translational Medicine.  24 March 2010: Vol 2 (24) 1-4.
  3. Diagnostic Technology <Retrieved on April 20,2010 at www.dhiusa.com>
  4. Biere, Barabara et.al. Influenza A H1N1 diagnostics: the first, the fastest, and the most reliable.  The Lancet.December 2009, volume 9.
  5. Poon, Leo et al.  Molecular Detection of a Novel Human Influenza (H1N1) of Pandemic Potential by Conventional and Rela-Time PCR Quantitative RT-PCR Assays.  Clinical Chemistry.  2009.  55:8, 1555-1558.

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