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INFLUENZA (20): H2N2 PANDEMIC POTENTIAL
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A ProMED-mail post
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International Society for Infectious Diseases
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Date: Thu 10 Mar 2011
Source: CIDRAP News [edited]
<http://www.cidrap.umn.edu/cidrap/conten ... 1h2n2.html>


Scientists say 1957 pandemic flu virus could return
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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, Maryland.

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 preemptive
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 percent 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 4600 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 [see the
archive ProMED-mail reports from 2005 listed below. - Mod.CP]. 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.

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

[byline: Robert Roos]

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[A convincing argument, but the diversity of the influenza A viruses
and their hosts somewhat diminishes the value of such predictions. -
Mod.CP]