Scientists say 1957 pandemic flu virus could return

Mar 10, 2011 (CIDRAP News) – A trio of vaccine researchers from the National Institutes of Health (NIH) says influenza A/H2N2 viruses, the subtype that caused the flu pandemic of 1957-58, could return and trigger a pandemic in much the same way the H1N1 subtype did in 2009.

The threat is significant enough to warrant devising a preemptive vaccination strategy, the scientists assert in a commentary published in this week's issue of Nature. The authors are Gary J. Nabel, Chih-Jen Wei, and Julie E. Ledgerwood, all of whom work at the NIH Vaccine Research Center in Bethesda, Md.

They write that H2N2 viruses have not circulated in humans for decades, with the result that people younger than 50 probably have little immunity to them. But such viruses are still circulating in pigs and birds and could jump back into humans, just as the 2009 H1N1 virus crossed from pigs to humans, they assert.

Drawing the parallel with the 2009 pandemic, Nabel and colleagues note that the hemagglutinin, or H1, component of the 2009 H1N1 virus is strikingly similar to the hemagglutinin of the H1N1 virus that caused the great 1918 flu pandemic.

The 1918 H1N1 virus evolved into widely divergent seasonal strains over the decades, but a version with a very similar hemagglutinin component has circulated in pigs for close to a century, changing little. That virus was "poised to cross back into humans and cause a new pandemic when broad protective human immunity had waned," the article says.

H2N2 "could reemerge in a similar way. Governments, regulatory agencies, and industry should develop a pre-emptive vaccination strategy," the researchers write.

After causing the pandemic of 1957-58, the H2N2 virus continued to circulate until it was displaced by the N3N2 virus in 1968, which triggered another pandemic and has continued to circulate ever since.

While H2N2 strains have not been found in humans for many years, they are still found in swine and birds, the scientists write. They add that H2N2 strains mutate fairly slowly, as the surface proteins in most bird and human strains are 92% identical.

Between 2003 and 2007, the authors tested 90 people for antibodies to H2N2 viruses. "Our study suggests that people under 50 have little or no immunity, and resistance dramatically increases for those over 50," they write, while cautioning that the findings need to be replicated in much larger numbers of people.

"The low mutation rate for H2N2, and evidence of waning human immunity, make it likely that an H2N2 pandemic could arise from animals," Nabel and colleagues assert.

The genetic similarity of existing H2N2 strains suggests that the type of vaccine used decades ago would still be protective, they go on to say. They suggest several possible preemptive vaccination strategies: manufacturing the vaccine licensed in 1957 and immunizing enough people globally to create herd immunity; making and stockpiling enough of the vaccine so supplies are ready in case of an outbreak; or making only "master lots" of the vaccine and start production when an outbreak occurs.

The argument by Nabel and colleagues is taken seriously by some other influenza experts.

Richard J. Webby, PhD, director of the World Health Organization Collaborating Center for Studies on the Ecology of Influenza in Animals and Birds, based at St. Jude Children's Hospital in Memphis, commented, "There is little doubt that H2 viruses pose a pandemic threat and a defendable argument can even be made, as Dr Nabel and team have done, that they pose more of a threat than many of the other subtypes of influenza viruses circulating in birds.

"Although we have not specifically identified an H2N2 virus in our surveillance efforts in birds for a number of years, H2N3 and H2N9 viruses are not uncommon. There is little evidence that global swine populations are major reservoirs of H2 viruses, but they are occasionally reported." He added that any virus with H2 hemagglutinin is a potential threat.

Michael T. Osterholm, PhD, MPH, welcomed the commentary as an important warning.

"I think it’s a reminder that just as we were surprised by H1N1 returning, we shouldn't be surprised by the potential for H2N2 returning. I think in this case, [Nabel] has really provided a very important perspective," said Osterholm, who is director of the University of Minnesota Center for Infectious Disease Research and Policy, publisher of CIDRAP News.

He said the commentary is a good reminder of other potential pandemic threats at a time when considerable attention is focused once again on H5N1 avian flu outbreaks and H5N1 cases in people.

Osterholm also commented that pigs played a key role in triggering the 2009 pandemic, whereas the 1957 virus came from birds, adding, "We surely have to keep our eye on the pig population, but we know that birds can be an important source too."

H2N2 viruses were at the center of a scare in 2005, when a Cleveland company working for the College of American Pathologists included H2N2 viruses in kits sent to more than 4,600 laboratories for proficiency testing. When this was discovered, the US Centers for Disease Control and Prevention asked all the labs to destroy the samples.

Authorities said at the time that most people had little or no immunity to the virus, since it hadn't circulated in humans since 1968. The incident prompted health authorities to recommend using biosafety level 3 (BSL-3) precautions when working with the virus, instead of the previous BSL-2.

Nabel GJ, Wei CJ, Ledgerwood JE. Vaccinate for the next H2N2 pandemic now. (Commentary) Nature 2011 Mar 10;471(7337):157-8 [Access page]

See also:

May 3, 2005, CIDRAP News story "All H2N2 flu virus samples destroyed, CDC says"

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