Commentary
Hoarding of Influenza Sequences Increases Pandemic Concerns
Recombinomics Commentary 20:55
May 30, 2008
In view of the possible threat posed by H7 viruses, the National Institute of Allergy and Infectious Diseases (NIAID) is sponsoring several studies of human H7 vaccines, according to NIAID Director Dr. Anthony S. Fauci.
A phase 1-2 clinical trial of a vaccine based on a US H7N7 virus was launched in March, Fauci told CIDRAP News today. The trial, based at Baylor School of Medicine in Houston, involves 125 volunteers who received doses ranging from 7.5 to 90 micrograms of antigen to study the vaccine's safety and immunogenicity. The egg-based vaccine was made by Sanofi, he said.
In addition, the NIAID recently conducted an intramural phase 1 clinical trial of a cold-adapted H7N3 vaccine made from the British Columbian strain, Fauci reported. He said the results show that the vaccine is safe, but the immunogenicity findings are still being analyzed.
Fauci said some additional research on H7 vaccines is under way in NIAID labs in Bethesda, Md. "The bottom line is there is stuff going on," he said.
The above comments describe some of the H7 vaccine projects ongoing with North American sequences. This update was presented in response to this week’s PNAS paper on increased affinities for human receptors by North American isolates in general, and the H7N2 isolate, A/New York/107/2003.
However, there is no H7N2 in the detailed programs in part because the increased binding of the isolate to human receptors and the ferret to ferret transmission was not well appreciated until these properties were described in last year’s J Virol paper and this week’s PNAS paper.
However, those activities have come under a cloud since the underlying sequences were pulled shortly after being made public. The sequences were made public at the end of last month, and pulled this month. The significance of the removal remains unclear because the removal was not mentioned in interviews associated with the publication, or follow-up comments or stories.
If the removed sequences represent the virus that infected the patient in 2002, then the virus is more dangerous than presented in the paper, because the New York patient would have almost certainly have been infected by another person. On the other hand, if the sequences deposited represent a lab artifact, then much of the data associated with the isolate would have to be re-evaluated or repeated with the virus that actually infected the patient.
If the virus truly is a human / avian reassortant, then the strain would be subject to more intense research and surveillance, coupled with an increase in vaccine studies (and would have been listed above).
The current fiasco associated with this virus is largely linked to sequence hoarding. A full sequence should have been generated before the animal studies were initiated. Instead, it seems that at best only HA and NA were sequenced and the presence of human genes was not known until 4 ½ years after the infection and after the sequences were made public last month.
Since the virus has been in the lab for over 4 years, there was ample time to generate a complete sequence. It is ironic that the same lab that has been deliberately creating human / avian reassortants in the lab, either accidentally created such a reassortant, or has been growing or maintaining a reassortant for the past four years in the absence of any real analysis.
Unfortunately, this sequence hoarding extends to most of the WHO regional labs, which can use the NIAID sequencing program to generate sequences on all eight gene segments at no cost, but have elected to generate sequences in house to control (and hoard) the data.
WHO has called for a paradigm shift on the sharing of information on influenza research, and is long over for such a shift to begin at WHO, where WHO consultants hoard the data in their labs and the WHO private sequence repository.
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