Middle-aged individuals may be in a perpetual state of H3N2 flu virus susceptibility
Individuals' immunological imprint from early childhood infection likely lessens severity but does not prevent infection

Date:
September 11, 2020
Source:
University of Pennsylvania School of Medicine
Summary:
Researchers have found that middle-aged individuals -- those born in
the late 1960s and the 1970s -- may be in a perpetual state of H3N2
influenza virus susceptibility because their antibodies bind to H3N2
viruses but fail to prevent infections, according to a new study.



FULL STORY ==========================================================================
Penn Medicine researchers have found that middle-aged individuals --
those born in the late 1960s and the 1970s -- may be in a perpetual state
of H3N2 influenza virus susceptibility because their antibodies bind to
H3N2 viruses but fail to prevent infections, according to a new study
led by Scott Hensley, PhD, an associate professor of Microbiology at
the Perelman School of Medicine at the University of Pennsylvania. The
paper was published today in Nature Communications.


==========================================================================
"We found that different aged individuals have different H3N2 flu virus antibody specificities," Hensley said. "Our studies show that early
childhood infections can leave lifelong immunological imprints that
affect how individuals respond to antigenically distinct viral strains
later in life." Most humans are infected with influenza viruses by three
to four years of age, and these initial childhood infections can elicit
strong, long lasting memory immune responses. H3N2 influenza viruses
began circulating in humans in 1968 and have evolved substantially over
the past 51 years. Therefore, an individual's birth year largely predicts
which specific type of H3N2 virus they first encountered in childhood.

Researchers completed a serological survey -- a blood test that measures antibody levels -- using serum samples collected in the summer months
prior to the 2017-2018 season from 140 children (ages one to 17) and
212 adults (ages 18 to 90). They first measured the differences in
antibody reactivity to various strains of H3N2, and then measured for neutralizing and non-neutralizing antibodies. Neutralizing antibodies
can prevent viral infections, whereas non- neutralizing antibodies can
only help after an infection takes place. Samples from children aged
three to ten years old had the highest levels of neutralizing antibodies against contemporary H3N2 viruses, while most middle- aged samples had antibodies that could bind to these viruses but these antibodies could
not prevent viral infections.

Hensley said his team's findings are consistent with a concept known as "original antigenic sin" (OAS), originally proposed by Tom Francis,
Jr. in 1960. "Most individuals born in the late 1960s and 1970s were immunologically imprinted with H3N2 viruses that are very different
compared to contemporary H3N2 viruses. Upon infection with recent H3N2
viruses, these individuals tend to produce antibodies against regions
that are conserved with older H3N2 strains and these types of antibodies typically do not prevent viral infections." According to the research
team, it is possible that the presence of high levels of non-neutralizing antibodies in middle-aged adults has contributed to the continued
persistence of H3N2 viruses in the human population. Their findings
might also relate to the unusual age distribution of H3N2 infections
during the 2017-2018 season, in which H3N2 activity in middle-aged and
older adults peaked earlier compared to children and young adults.

The researchers say that it will be important to continually complete
large serological surveys in different aged individuals, including
donors from populations with different vaccination rates. A better understanding of immunity within the population and within individuals
will likely lead to improved models that are better able to predict the evolutionary trajectories of different influenza virus strains.

"Large serological studies can shed light on why the effectiveness of
flu vaccines varies in individuals with different immune histories,
while also identifying barriers that need to be overcome in order to
design better vaccines that are able to elicit protective responses in
all age groups," said Sigrid Gouma, PhD, a postdoctoral researcher of Microbiology and first author on the paper.

Other Penn authors include Madison Weirick and Megan E. Gumina. Additional authors include Angela Branche, David J. Topham, Emily T. Martin,
Arnold S.

Monto, and Sarah Cobey.

This work was supported by the National Institute of Allergy and
Infectious Diseases (1R01AI113047, S.E.H.; 1R01AI108686, S.E.H.;
1R01AI097150, A.S.M.; CEIRS HHSN272201400005C, S.E.H., S.C., E.T.M.,
A.S.M. A.B., D.J.T.) and Center for Disease Control (U01IP000474,
A.S.M.). Scott E. Hensley holds an Investigators in the Pathogenesis of Infectious Disease Awards from the Burroughs Wellcome Fund.


========================================================================== Story Source: Materials provided by University_of_Pennsylvania_School_of_Medicine. Note: Content may be
edited for style and length.


========================================================================== Journal Reference:
1. Sigrid Gouma, Kangchon Kim, Madison E. Weirick, Megan E. Gumina,
Angela
Branche, David J. Topham, Emily T. Martin, Arnold S. Monto,
Sarah Cobey, Scott E. Hensley. Middle-aged individuals may be in
a perpetual state of H3N2 influenza virus susceptibility. Nature
Communications, 2020; 11 (1) DOI: 10.1038/s41467-020-18465-x ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/09/200911141751.htm

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