H5N1 mutations, other details unveiled at H5N1 meeting

Apr 3, 2012 (CIDRAP News) – New details about H5N1 transmission studies emerged today during a Royal Society conference on the topic in London, but with Dutch export restrictions blocking what one research group could share.

Scientists who led the two studies in question both took the stage during the first day of a 2-day meeting to discuss a host of issues on the topic, from basic research to ethics. The Royal Society is offering a live webcast of the meeting.

Fresh information about the two controversial studies comes just days after the National Science Advisory Board for Biosecurity (NSABB) reversed an earlier recommendation that the studies be published in redacted form, due to concerns about an accidental or intentional release of the modified H5N1 viruses.

Yoshihiro Kawaoka, DVM, PhD, who leads a group from the University of Wisconsin, Madison, gave a detailed look at his team's H5N1 studies on ferrets. He highlighted four mutations that his group produced, one of which is found in nature. Three of the mutations were on the head of the virus, and one was on the stalk. The findings are slated to appear in a future issue of Nature.

He said using a hybrid between H5N1 and the 2009 H1N1 virus allowed his group to focus on the hemagglutinin portion. Kawaoka added that the mutant strains weren't lethal to the animals and that the pathogenicity was less than that of the 2009 pandemic virus.

Viruses containing the mutations were highly sensitive to antiviral drugs, and they reacted to sera from humans vaccinated against H5N1, he said. Kawaoka added that his group's data could have implications for public health policymakers. "Our information allows us to find the right virus for the production of stockpiled vaccines," he added.

One of the mutations—the one found in nature—had loss of a glycosylation site, a characteristic that Kawaoka said is linked to transmissibility in humans, and a pattern increasingly seen in countries such as Egypt in which the H5N1 virus has infected humans. "We can use the information to understand what's happening in nature," he said, adding that better surveillance is needed to assess the risk of circulating strains.

Kawaoka also gave a detailed view of his lab's biosecurity measures, which are based on US government regulations and adhere to agricultural biosafety level 3 (BSL-3). He said the term "enhanced BSL-3" is nonspecific, and that more efforts are needed to better define the security terms.

Though the other research group, led by Ron Fouchier, PhD, at Erasmus University in the Netherlands, used a different virus strain in their ferret studies, "we found striking similarity—mechanistically, a very interesting finding," Kawaoka said.

However, Fouchier said today that he could only share the redacted version of his study at the conference, because the Dutch government hasn't yet lifted export controls on the information.

While he couldn't disclose the mutations, he said the two studies provide more unanimous expert advice to countries that battle H5N1 threats. The group's findings will be published in an upcoming issue of Science.

Though the NSABB's reversal helps clear the way for publication in the two journals, the status of a voluntary moratorium on H5N1 research is unclear. In February a World Health Organization (WHO) expert panel recommended a host of measures, which included a research moratorium, pending a biosafety review of the practices at the labs.

Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases (NIAID), told CIDRAP News today that regularly scheduled, detailed safety reviews of the labs were already in progress when the WHO recommendations came out, unbeknownst to that group. He said an extra round of reviews won't be conducted, given that they have been done multiple times and very recently.

He said the Dutch government is as strict as the United States is with research biosafety issues, and that the Erasmus group—like the Wisconsin group— has also met or exceeded safety guidelines.

A panel from the Dutch government that is similar to the NSABB meets on Apr 23 and 24 to address the export restriction, Fauci said.

During today's presentations, more details emerged about last week's NSABB meeting to consider revised versions of the two studies.

Paul Keim, PhD, acting director of the NSABB and a microbial geneticist at Northern Arizona University, said the board's decision to reverse its recommendation was influenced by clarifications from Fouchier's group. He said those details were included in "an additional 1,000 words from Science" and in confidential and yet-unpublished data on the evolution of the virus.

Due to US export controls in place at the time, as well as those from the Dutch government, the NSABB didn't have access to the revised papers ahead of time and had only 2 hours to review the revisions at the meeting, Keim said.

The Erasmus group's paper had not undergone a review yet by Science, so observers shouldn't read too much into the differences in wording that the NSABB used in its statement when referring to the two different papers, he added.

Keim said the new US policy on oversight of federally funded life sciences dual-use research is a step in the right direction, and that a system to flag and monitor issues earlier in the process was lacking. He predicted that more steps will be needed in the years ahead to address similar issues.

"We're at a brink in synthetic biology, and technology is changing so much faster than the moral compass," he said.

One theme that wove through several of the Royal Society presentations today is the need for more discussion to tackle issues related to H5N1 transmission research. Keim and many of the other presenters said scientists need to come up with a framework and guidelines themselves to avoid lawmakers stepping in to steer policies, which would likely be even more burdensome.

Thomas Inglesby, MD, PhD, director of the Center for Biosecurity at the University of Pittsburgh Medical Center, urged researchers to extend the voluntary moratorium until there is wide agreement on how to proceed. He added that experts have worked through the risks and benefits in a transparent way, including participants from outside the United States and Europe.

He also said the work should be limited to as few labs as possible and that a top priority should be improving the capacity to quickly produce larger quantities of better H5N1 vaccines.

The Royal Society program continues tomorrow, with discussions on news and publishing, funding, ethics, the vaccine industry, and public involvement, with time devoted to open discussions.

See also:

Royal Society webcast link

Apr 2 CIDRAP News story "Major players weigh implications of NSABB H5N1 reversal"

Mar 30 CIDRAP News story "NSABB reverses recommendation on H5N1 studies"

Mar 29 CIDRAP News story "US debuts life sciences dual-use research policy"

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