CDC post on Avian Influenza (Bird Flu) Research
It discusses previous GOF work performed at the CDC which consisted of making reassortants between H5N1 and human flu viruses (published 2006) and between H5N1 and H3N2 (published 2009) “as part of pandemic preparedness efforts”. Some 5-8 years on and one pandemic later we see that such reassortants haven’t yet emerged. This is not a criticism of the work, just another observation as to the difficulties of predicting influenza virus evolution.
Mutations around the H5 receptor binding site tended to attenuate the virus which would require compensating mutations to acquire pathogenicity. They suggested that “extensive evolution of H5N1 viruses would be need to occur before these H5N1 viruses could become fully transmissible in humans”. As we know Fouchier and Kawaoka succeeded with a handful of mutations.
Under the heading “…what is the purpose of this research?” two paragraphs are worth noting:
“Typically, the purpose of this research is to identify dangerous mutations in existing viruses so that global surveillance efforts can monitor for these mutations in circulating flu viruses. These studies also have the potential to predict what dangerous viruses might emerge in nature before they actually emerge, which allows interventions such as vaccines and drugs to be developed before nature produces the next pandemic virus.
One of the biggest challenges of current flu vaccine development is the lag time between when a virus is first identified and when a vaccine can be manufactured and distributed to the public to protect against that virus. In the United States, the composition of the flu vaccine is decided in February, but due to technological and other limitations, the manufactured vaccine typically does not become available until July or later. Proponents of gain of function research hope to overcome the time constraints of vaccine production by preparing and manufacturing vaccines in advance to protect against flu viruses before they emerge in nature.”
The utility of this work in terms of developing proactive drugs and vaccines has been challenged, at least given present approaches (Mahmoud, 2013; Wain-Hobson, 2014).
For the moment, industry needs to know the strain to beat.
The interpretation of mutations in field isolates is complicated by the genetic background of the strain. The surest way to ascertain the impact of a mutation of concern is to first isolate the virus and test it in a ferret aerosol transmission assay. “CDC does conduct transmissibility studies using naturally occurring (not altered) HPAI viruses in animal models to assess their transmissibility. This research informs CDC’s risk assessments of novel flu viruses.”
Small point
The document lists the 15 select agents that fall under DURC umbrella. They include the eradicated variola and rinderpest viruses. It does not include human influenza H2H2 which caused the Asian flu pandemic in 1957. This virus is no longer circulating and given that the majority of the world’s population is <50 years old there is no herd immunity (Nabel et al., 2011).
H2N2 viruses are circulating in pigs and birds. In the UK, the H2N2 pandemic virus is handled in a BSL4 lab.
References
Mahmoud, A. Gain-of-function research: unproven technique. Science. 2013 Oct 18;342(6156):310-1. doi: 10.1126/science.342.6156.310-b.
Nabel GJ, Wei CJ, Ledgerwood JE. Vaccinate for the next H2N2 pandemic now. Nature. 2011 Mar 10;471(7337):157-8. doi: 10.1038/471157a.
Wain-Hobson, S. The irrationality of GOF avian influenza research. Frontiers in Public Health 2, 77 2014 doi: 10.3389/fpubh.2014.00077
An interesting comment on preventive flu vaccination is to be found on the NHS website (10 March 2011)
